Left Anterior Fascicular Block After Transcatheter Closure of Ventricular Septal Defect in Children

Background: Arrhythmia is the most common complication after transcatheter closure of a ventricular septal defect (VSD). However, the effects of postprocedural left anterior fascicular block are not clear. This study presents the clinical characteristics, prognosis, and related risk factors of left anterior fascicular block after transcatheter closure of a VSD in children.Methods: The clinical and follow-up data of the patients in the Heart Center of Children's Hospital of Chongqing Medical University from June 2009 to October 2018 were reviewed. And 30 cases were eligible out of all 1,371 cases.Results: An electrocardiogram showed a left anterior fascicular block within 3 days, and most patients gradually returned to normal within 1–2 years, showing a dynamic change. Left ventricular end-diastolic dimension Z-score ranged from −2 to 2 in all children, and no decrease of left ventricular ejection fraction was found in all children. The high ratio between VSD size and body surface area [p < 0.05, odds ratio (OR) 2.6, 95% CI: 1.136–6.113] and large diameter difference between the occluder size and VSD size (p < 0.05, OR 2.1, 95% CI: 1.036–4.609) were independent risk factors for postprocedural left anterior fascicular block.Conclusions: The incidence of postprocedural left anterior fascicular block is not that low, and the overall prognosis is quite good at the current follow-up stage. No progressive severity has been found, such as complete left bundle branch block, double (triple) bundle branch block, and atrioventricular block, to have an influence on cardiac systolic and diastolic function

Blocking interaction between SHP2 and PD‐1 denotes a novel opportunity for developing PD‐1 inhibitors

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis

CT−based radiomics signature for differentiating pyelocaliceal upper urinary tract urothelial carcinoma from infiltrative renal cell carcinoma

ObjectivesTo develop a CT-based radiomics model and a combined model for preoperatively discriminating infiltrative renal cell carcinoma (RCC) and pyelocaliceal upper urinary tract urothelial carcinoma (UTUC), which invades the renal parenchyma.Materials and methodsEighty patients (37 pathologically proven infiltrative RCCs and 43 pathologically proven pyelocaliceal UTUCs) were retrospectively enrolled and randomly divided into a training set (n = 56) and a testing set (n = 24) at a ratio of 7:3. Traditional CT imaging characteristics in the portal venous phase were collected by two radiologists (SPH and ZXL, who have 4 and 30 years of experience in abdominal radiology, respectively). Patient demographics and traditional CT imaging characteristics were used to construct the clinical model. The radiomics score was calculated based on the radiomics features extracted from the portal venous CT images and the random forest (RF) algorithm to construct the radiomics model. The combined model was constructed using the radiomics score and significant clinical factors according to the multivariate logistic regression. The diagnostic efficacy of the models was evaluated using receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC).ResultsThe RF score based on the eight validated features extracted from the portal venous CT images was used to build the radiomics model. Painless hematuria as an independent risk factor was used to build the clinical model. The combined model was constructed using the RF score and the selected clinical factor. Both the radiomics model and combined model showed higher efficacy in differentiating infiltrative RCC and pyelocaliceal UTUC in the training and testing cohorts with AUC values of 0.95 and 0.90, respectively, for the radiomics model and 0.99 and 0.90, respectively, for the combined model. The decision curves of the combined model as well as the radiomics model indicated an overall net benefit over the clinical model. Both the radiomics model and the combined model achieved a notable reduction in false-positive and false-negativerates, resulting in significantly higher accuracy compared to the visual assessments in both the training and testing cohorts.ConclusionThe radiomics model and combined model had the potential to accurately differentiate infiltrative RCC and pyelocaliceal UTUC, which invades the renal parenchyma, and provide a new potentially non-invasive method to guide surgery strategies

Depositing boron on Cu(111): Borophene or boride?

Large-area single-crystal surface structures were successfully prepared on Cu(111) substrate with boron deposition, which is critical for prospective applications. However, the proposed borophene structures do not match the scanning tunneling microscopy (STM) results very well, while the proposed copper boride is at odds with the traditional knowledge that ordered copper-rich borides normally do not exist due to small difference in electronegativity and large difference in atomic size. To clarify the controversy and elucidate the formation mechanism of the unexpected copper boride, we conducted systematic STM, X-ray photoelectron spectroscopy and angle-resolved photoemission spectroscopy investigations, confirming the synthesis of two-dimensional copper boride rather than borophene on Cu(111) after boron deposition under ultrahigh vacuum. First-principles calculations with defective surface models further indicate that boron atoms tend to react with Cu atoms near terrace edges or defects, which in turn shapes the intermediate structures of copper boride and leads to the formation of stable Cu-B monolayer via large-scale surface reconstruction eventually.Comment: 15 pages, 4 figure

Identification and characterization of IgNAR and VNAR repertoire from the ocellate spot skate (Okamejei kenojei)

Elasmobranchs are crucial for comparative studies of evolution, as they belong to the most ancient vertebrate lineages that survived numerous extinction events and persist until today. The immunoglobulin new antigen receptor (IgNAR) found in sharks and heavy-chain-only antibody (HCAb) found in camelidae are products of convergent evolution. Although it was previously believed that IgNAR emerged 220 million years ago, before the divergence of sharks and skates, there is limited evidence to support this. In this study, we provide data supporting the existence of IgNAR in the ocellate spot skate (Okamejei kenojei) mononuclear cell transcriptome and peripheral blood serum. Additionally, we characterize the germline gene configuration of the ocellate spot skate IgNAR V domain. The ocellate spot skate IgNAR structure prediction and VNAR crystal structure exhibit high similarity to their shark counterparts. These data strongly suggest that IgNAR in both sharks and skates share a common ancestor. Sequencing of the ocellate spot skate VNAR repertoire provided crucial data for further understanding of the IgNAR generation. Notably, we discovered that approximately 99% of the ocellate spot skate VNARs belonged to type IV. This represents an exceptionally high proportion of type IV within the VNAR repertoire, which has not been documented in previously studied elasmobranchs. This unique characteristic of the ocellate spot skate VNAR adds essential structural diversity to the naïve VNAR library from elasmobranchs and could potentially benefit the development of pharmaceutical drugs

New early oligocene zircon U-Pb dates for the ‘Miocene’ Wenshan Basin, Yunnan, China: Biodiversity and paleoenvironment

The sedimentary basins of Yunnan, Southwest China, record detailed histories of Cenozoic paleoenvironmental change. They track regional tectonic and palaeobiological evolution, both of which are critically important for the development of modern floral diversity in southwestern China and throughout Asia more generally. However, to be useful, the sedimentary archives within the basins have to be placed within a well-constrained timeframe independent of biostratigraphy. Using high resolution U-Pb dating, we redefine the age of fossil-bearing strata in the Wenshan Basin. Regarded as Miocene for the last half century, these basin sediments encompass 30±2 and 32±1 Ma early Oligocene tuffaceous horizons, thus indicating a significantly greater antiquity than previously recognized. Together with other regional age revisions our result points to widespread Yunnan basin and orographic development as largely having taken place by the end Paleogene. This age revision provides an important new perspective on the preserved biotas and their evolution in Yunnan, and especially our understanding of the origin of Asian biodiversity which, regionally, had a near-modern composition by the early Oligocene. Crucially, this revised age evidences late Eocene-early Oligocene regional tectonism, pointing to the rise of eastern Tibet and the Hengduan Mountains before the growth of the Himalaya, and that Asia's high plant diversity has a Paleogene origin

DependData: data collection dependability through three-layer decision-making in BSNs for healthcare monitoring

Recently, there have been extensive studies on applying security and privacy protocols in Body Sensor Networks (BSNs) for patient healthcare monitoring (BSN-Health). Though these protocols provide adequate security to data packets, the collected data may still be compromised at the time of acquisition and before aggregation/storage in the severely resource-constrained BSNs. This leads to data collection frameworks being meaningless or undependable, i.e., an undependable BSN-Health. We study data dependability concerns in the BSN-Health and propose a data dependability verification framework named DependData with the objective of verifying data dependability through the decision-making in three layers. The 1st decision-making (1-DM) layer verifies signal-level data at each health sensor of the BSN locally to guarantee that collected signals ready for processing and transmission are dependable so that undependable processing and transmission in the BSN can be avoided. The 2nd decision-making (2-DM) layer verifies data before aggregation at each local aggregator (like clusterhead) of the BSN to guarantee that data received for aggregation is dependable so that undependable data aggregation can be avoided. The 3rd decision-making (3-DM) layer verifies the stored data before the data appears to a remote healthcare data user to guarantee that data available to the owner end (such as smartphone) is dependable so that undependable information viewing can be avoided. Finally, we evaluate the performance of DependData through simulations regarding 1-DM, 2-DM, and 3-DM and show that up to 92% of data dependability concerns can be detected in the three layers. To the best of our knowledge, DependData would be the first framework to address data dependability aside from current substantial studies of security and privacy protocols. We believe the three layers decision-making framework would attract a wide range of applications in the future