Search

Abstract: Protein-ligand interactions are necessary for majority protein functions. Adenosine- 5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is costineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

Objective The aim of this study was to confirm the pathogenic variants, explore the genotype–phenotype correlation and characteristics of Chinese patients with Treacher Collins syndrome (TCS). Design Clinical details of 3 TCS family cases and 2 sporadic cases were collected and analyzed. Whole-exome sequencing and Sanger sequencing were conducted to detect causative variants. Setting Tertiary clinical care. Patients This study included 8 patients clinically diagnosed with TCS who were from 3 familial cases and 2 sporadic cases. Main Outcome Measures When filtering the database, variants were saved as rare variants if their frequency were less than 0.005 in the 1000 Genomes Project Database, the Exome Aggregation Consortium (ExAC) browser, and the Novogene database, or they would be removed as common ones. The pathogenic variants identified were verified by polymerase chain reaction. The sequencing results were analyzed by Chromas 2.1 software. Results Two novel pathogenic variants (NM_000356.3: c.537del and NM_000356.3: c.1965_1966dupGG) and 2 known pathogenic variants (NM_000356.3: c.1535del, NM_000356.3: c.4131_4135del) were identified within TCOF1 which are predicted to lead to premature termination codons resulting in a truncated protein. There was a known missense SNP (NM_015972.3: c.139G>A) within POLR1D. No phenotype–genotype correlation was observed. Instead, these 8 patients demonstrated the high genotypic and phenotypic heterogeneity of TCS. Conclusions This study expands on the pathogenic gene pool of Chinese patients with TCS. Besides the great variation among patients which is similar to international reports, Chinese patients have their own characteristics in clinical phenotype and pathogenesis mutations.

Background Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. Purpose To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. Study type Prospective. Population Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). Field strength/sequence A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. Assessment The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. Statistical tests Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P Results Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). Data conclusions This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. Evidence level 2 TECHNICAL EFFICACY: Stage 2.

Background: The incidence of oral squamous cell carcinoma (OSCC) is increasing, with an estimated 369,000 new patients each year worldwide. Surgery is the primary treatment modality for early-stage OSCC, but there is scant evidence to prove the value of elective neck dissection (END) for relatively small early-stage OSCC. This study aimed to identify factors predicting survival for patients with clinical stage T1N0M0 (cT1N0M0) OSCC and whether up-front END improved survival. Patients and Methods: Patients with cT1N0M0 OSCC who underwent tumor resection with or without END were identified and extracted from the SEER database. Kaplan-Meier survival analysis was used to assess overall survival and disease-specific survival. Prognostic factors were determined using Cox regression analysis. Results: A total of 5,752 patients with cT1N0M0 OSCC were extracted, of whom 2,194 (38.1%) underwent tumor resection surgery with concurrent END and 3,558 (61.9%) underwent only tumor resection. In a multivariate Cox analysis, a relatively advanced age (>62 years) and relatively high pathologic grade were the significant negative predictors, but married status (hazard ratio, 0.709; P=.006) and undergoing END (hazard ratio, 0.708; PConclusions: Patients with cT1N0M0 OSCC gain significant overall and disease-specific survival benefit from END.

Background: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. Objective: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment. Methods: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population–based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome. Results: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P

Clouds and cloud shadows heavily affect the quality of the remote sensing images and their application potential. Algorithms have been developed for detecting, removing, and reconstructing the shaded regions with the information from the neighboring pixels or multisource data. In this article, we propose an integrated cloud detection and removal framework using cascade convolutional neural networks, which provides accurate cloud and shadow masks and repaired images. First, a novel fully convolutional network (FCN), embedded with multiscale aggregation and the channel-attention mechanism, is developed for detecting clouds and shadows from a cloudy image. Second, another FCN, with the masks of the detected cloud and shadow, the cloudy image, and a temporal image as the input, is used for the cloud removal and missing-information reconstruction. The reconstruction is realized through a self-training strategy that is designed to learn the mapping between the clean-pixel pairs of the bitemporal images, which bypasses the high demand of manual labels. Experiments showed that our proposed framework can simultaneously detect and remove the clouds and shadows from the images and the detection accuracy surpassed several recent cloud-detection methods; the effects of image restoring outperform the mainstream methods in every indicator by a large margin. The data set used for cloud detection and removal is made open.

This study aimed to determine the mechanism of isogeneic-induced pluripotent stem cells (iPSCs) homing to vascular transplants and their therapeutic effect on chronic allogeneic vasculopathy. We found that integrin β1 (Intgβ1) was the dominant integrin β unit in iPSCs that mediates the adhesion of circulatory and endothelial cells (ECs). Intgβ1 knockout or Intgβ1-siRNAs inhibit iPSC adhesion and migration across activated endothelial monolayers. The therapeutic effects of the following were examined: iPSCs, Intgβ1-knockout iPSCs, iPSCs transfected with Intgβ1-siRNAs or nontargeting siRNAs, iPSC-derived ECs, iPSC-derived ECs simultaneously overexpressing Intgα4 and Intgβ1, iPSCs precultured in endothelial medium for 3 days (endothelial-prone stem cells), primary aortic ECs, mouse embryonic fibroblasts, and phosphate-buffered saline (control). The cells were administered every 3 days for a period of 8 weeks. iPSCs, iPSCs transfected with nontargeting siRNAs, and endothelial-prone stem cells selectively homed on the luminal surface of the allografts, differentiated into ECs, and decreased neointimal proliferation. Through a single administration, we found that iPSCs trafficked to allograft lesions, differentiated into ECs within 1 week, and survived for 4-8 weeks. The therapeutic effect of a single administration was moderate. Thus, Intgβ1 and pluripotency are essential for iPSCs to treat allogeneic vasculopathy.

Stroke is the leading cause of death and adult disability worldwide. Mitochondrial dysfunction is one of the hallmarks of stroke-induced neuronal death, and maintaining mitochondrial function is essential in cell survival and neurological progress following ischemic stroke. Stem cell-mediated mitochondrial transfer represents an emerging therapeutic approach for ischemic stroke. Accumulating evidence suggests that mesenchymal stem cells (MSCs) can directly transfer healthy mitochondria to damaged cells, and rescue mitochondrial damage-provoked tissue degeneration. This review summarizes the research on MSCs-mediated mitochondrial transfer as a therapeutic strategy against ischemic stroke.

Appearances and qualities of remote sensing images are affected by different atmospheric conditions, quality of sensors, and radiometric calibrations. This heavily challenges the generalization abi...

The application of deep learning in industry often needs to train large-scale neural networks and use large-scale data sets. However, larger networks and larger data sets lead to longer training time, which hinders the research of algorithms and the progress of actual engineering development. Data-parallel distributed training is a commonly used solution, but it is still in the stage of technical exploration. In this paper, we study how to improve the training accuracy and speed of distributed training, and propose a distributed training strategy based on hybrid gradient computing. Specifically, in the gradient descent stage, we propose a hybrid method, which combines a new warmup scheme with the linear-scaling stochastic gradient descent (SGD) algorithm to effectively improve the training accuracy and convergence rate. At the same time, we adopt the mixed precision gradient computing. In the single-GPU gradient computing and inter-GPU gradient synchronization, we use the mixed numerical precision of single precision (FP32) and half precision (FP16), which not only improves the training speed of single-GPU, but also improves the speed of inter-GPU communication. Through the integration of various training strategies and system engineering implementation, we finished ResNet-50 training in 20 minutes on a cluster of 24 V100 GPUs, with 75.6% Top-1 accuracy, and 97.5% GPU scaling efficiency. In addition, this paper proposes a new criterion for the evaluation of the distributed training efficiency, that is, the actual average single-GPU training time, which can evaluate the improvement of training methods in a more reasonable manner than just the improved performance due to the increased number of GPUs. In terms of this criterion, our method outperforms those existing methods.

Ischemic stroke is one of the leading causes of death and long-term disability worldwide. As an important class of pervasive genes involved in many pathophysiological processes of ischemic stroke, non-coding RNAs (ncRNAs) have received attention in the past decades. ncRNAs are a class of functional RNAs that regulate gene expression in a post-transcriptional manner, and including microRNAs, long non-coding RNAs, and circular RNAs. Several studies have deciphered that ncRNAs have a key role in the ischemic stroke-induced neuroinflammation and cell death via different molecules and pathways. Thus, ncRNAs show great promise as novel molecular targets in ischemic stroke. In this article, we provide an updated review of the current state of our knowledge about the roles of different types of ncRNAs in neuroinflammation and cell death following ischemic stroke, which may facilitate the translation of ncRNAs research into clinical practice to improve the clinical outcome of stroke therapy.

As a common type of joint used in spatial grid structures, the tensile performance of bolt-sphere joints directly affects the safety of the spatial grid structure under fire. To study the tensile properties of the bolts in sphere joints under fire, the four sets of 36 bolt-sphere joints consist of M20, M24, M30, and M36 high-strength bolts were conducted in elevated temperature by steady-state test. Therefore, the tensile bearing capacity of the bolt-sphere joint was obtained under different elevated temperatures. Experimental results show the destroyed section of the bolt-sphere joint that occurs in the thread of the high-strength bolt at the intersection of the sphere because of the maximum concentration of stresses that occurred in areas of destruction. The brittle fracture of bolt-sphere joints happened when the temperature is below 400 ℃. As the temperature increased, the neck shrinkage of the damaged section of the bolt becomes more apparent, and the ductile failure of the bolt-sphere joint occurred. The stiffness and the bearing capacity of bolt-sphere joints decreased gradually as the temperature rose. Conversely, the ductility was gradually increasing. When the temperature was greater than 300 ℃, the stiffness and the bearing capacity of the bolts in sphere joint decreased rapidly. The bearing capacity reduction coefficient of the high-strength bolts with different diameters were next to the same at elevated temperatures. According to the experimental data, the formulas of the tensile bearing capacity reduction coefficient of bolt-sphere joints were obtained.

Mobile payment generally refers to transactions made through the applications of a portable electronic gadget without the transfer of cash. As one of the most disruptive technologies for finance, mobile payment has been rapidly transforming the traditional financial industry. While it brings important benefits, there are also various risks, in terms of liquidity, security, and data privacy, that call for adequate regulatory responses. As a global financial centre, Hong Kong has gradually established a regulatory framework for mobile payment, addressing the relevant risks with rules on payment and privacy. However, there is still room for further improvement, in terms of measures to deal with cybersecurity issues and strengthen the protection of personal data. The Hong Kong experiences suggest that, to regulate a new and fast-growing industry such as mobile payment, the regulatory regime needs to be improved continuously to alleviate the risk concerns, so as to enhance the protection of financial consumers and society at large.

Objectives Carbapenem-resistant Enterobacteriaceae (CRE) are a major public-health threat. The most important mechanism of carbapenem resistance in CRE is carbapenemase production. Early identification of carbapenemase-producing Enterobacteriaceae (CPE) leads to improved clinical outcomes. This systematic review aimed to assess the accuracy and applicability of the modified Hodge test (MHT), the carbapenemase Nordmann–Poirel (Carba NP) test, the modified carbapenem inactivation method (mCIM) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) for CPE detection. Methods The meta-analysis included pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (SROC) curve and area under the curve (AUC). Results A total of 67 studies were included in the analysis. Pooled effect sizes (95% confidence interval) of the MHT, Carba NP, mCIM and MALDI-TOF/MS, respectively, were as follows: sensitivity, 92% (87–95%), 97% (94–98%), 99% (99–100%) and 99% (96–100%); specificity, 93% (86–97%), 100% (99–100%), 99% (96–100%) and 99% (96–100%); diagnostic odds ratio, 98.156 (48.175–199.995), 1277.710 (751.391–2172.692), 3597.352 (1287.575–10000) and 1781.360 (651.827–4868.228); and AUC, 0.97, 1, 1 and 1. Conclusion Carba NP, mCIM and MALDI-TOF/MS all demonstrated high accuracy in CPE detection, whereas the MHT is not recommended owing to some clear drawbacks. We recommend the selection of carbapenemase detection tests in the order of mCIM, Carba NP and MALDI-TOF/MS according to their simplicity, cost, and equipment and skills involved.

This study proposes an automatic building footprint extraction framework that consists of a convolutional neural network (CNN)-based segmentation and an empirical polygon regularization that transforms segmentation maps into structured individual building polygons. The framework attempts to replace part of the manual delineation of building footprints that are involved in surveying and mapping field with algorithms. First, we develop a scale robust fully convolutional network (FCN) by introducing multiple scale aggregation of feature pyramids from convolutional layers. Two postprocessing strategies are introduced to refine the segmentation maps from the FCN. The refined segmentation maps are vectorized and polygonized. Then, we propose a polygon regularization algorithm consisting of a coarse and fine adjustment, to translate the initial polygons into structured footprints. Experiments on a large open building data set including 181 000 buildings showed that our algorithm reached a high automation level where at least 50% of individual buildings in the test area could be delineated to replace manual work. Experiments on different data sets demonstrated that our FCN-based segmentation method outperformed several most recent segmentation methods, and our polygon regularization algorithm is robust in challenging situations with different building styles, image resolutions, and even low-quality segmentation.

On July 10-12th, 2016, IEEE International Conference on Service Operations and Logistics, and Informatics (SOLI), IEEE International Conference on Vehicular Electronics and Safety (ICVES), and IEEE International Forum on Integrated and Sustainable Transportation Systems (FISTS) were held together in Beijing, China. These three conferences were organized by the State Key Laboratory for Management and Control of Complex Systems (SKL-MCCS), Institute of Automation, Chinese Academy of Sciences, China and Chinese Association of Automation. With continuous efforts and improvement, IEEE SOLI, ICVES, and FISTS have already become an influential event and good communication platform. The scholars, researchers and practitioners have been attracted from academic institutions, universities and industrial companies all over the world, focusing mainly on SOLI, VES, and ISTS. More than one hundred participants from various countries had deep discussions on definition, challenges and alternative solutions for SOLI, VES and ISTS areas. These conferences were honored to have 7 distinguished keynote speakers, who shared their ideas, studies, field applications, and vision of parallel intelligence for future research and industrial directions. The theory of parallel intelligence can thus be seen widely applied to a variety of areas including parallel transportation management systems, parallel driving, parallel blockchain, parallel testing, parallel networks and other areas.

Objective: To observe the therapeutic effect of acupuncture-moxibustion at different intervals on persistent allergic rhinitis. Methods: A total of 90 patients conforming to the inclusion criteria were randomized into three groups named A, B and C by randomized block method. Patients in all three groups received the same treatment of acupuncture and herbal cake-partitioned moxibustion at the same acupoints, while the treatment frequency was different. Patients in group A received the treatment once a week, group B twice a week and group C three times a week, and all the treatment lasted for 4 weeks. The total nasal symptom score (TNSS), total ocular symptom score (TOSS) and Sino-nasal outcome test-20 (SNOT-20) were evaluated before and after treatment. The self-rating score of symptoms was evaluated during treatment and 2 weeks after treatment. Results: The total effective rate was 80.0% in group A, 93.3% in group B, and 100.0% in group C. The total effective rate in group A was statistically different from that in group B and group C (both P 0.05). After treatment, scores of TNSS, TOSS and SNOT-20 in all three groups dropped significantly, and statistically different from those before treatment (all P 0.05); after 4-week treatment, the score in group A was higher than that in group B and group C, and showed statistical significant (both P 0.05). Conclusion: All three protocols are effective for allergic rhinitis. With the increase of treatment frequency, the therapeutic efficacy with a treatment frequency of twice a week and three times a week is superior to that of once a week. Frequency of three times a week has a better long-term effect than once and twice a week, together with the least fluctuation of symptoms.

Background Pancreatic ductal adenocarcinoma has a devastatingly poor prognosis, and most prognostic factors reflected the tumor stage more than the tumors' biology. The peripheral nerve plexus is densely distributed in the tumor micro-environment, and there are interactions between tumor cells and these nerves. Perineural invasion is an important risk factor for tumor recurrence and metastasis in pancreatic head adenocarcinoma, but the concrete types of extrapancreatic neuropathy and its role in predicting prognosis are still not clear. Objective To clarify the role of extrapancreatic neuropathy in the early postoperative liver metastasis and tumor-related mortality in pancreatic head adenocarcinoma and to study the mechanism of tumor recurrence and liver metastasis in pancreatic head adenocarcinoma. Methods We reported a retrospective study of 60 patients with resectable pancreatic head adenocarcinoma, all of whom accepted radical pancreaticoduodenectomy. Plexus pancreaticus capitalis II (PLX-II) was the representation of extrapancreatic plexus in our study, and all of these plexus had immunohistochemical staining. We defined the postoperative tumor recurrence and tumor-related mortality within 6 months as the early prognostic indicators and analyzed the pathological alterations in PLX-II among different prognosis groups. Results There were 18 patients suffering early postoperative liver metastasis; these two groups differed significantly in the average number of nerve trunks (P

Pengfei Sun, Meng Lu, Changchen Wang, Bo Pan Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of ChinaCorrespondence: Bo PanDepartment of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of ChinaTel +8613810855912Email zbzbzhc@163.comPurpose: This study evaluated the utility of a ruler for reconstructed article positioning.Methods: Forty-seven patients with unilateral microtia were selected from August 2020 to September 2021.Results: The linear distance from the highest point of the reconstructed auricle to the central axis of the nose was not significantly different from the distance from the highest point of the normal contralateral auricle to the central axis of the nose (P> 0.05). The distance from the lowest point of the reconstructed auricle to the central axis of the nose was not significantly different from the distance from the lowest point of the normal auricle to the central axis of the nose (P> 0.05). The linear distance from the highest to the lowest point of the reconstructed auricle was not significantly different from the distance from the highest to the lowest point of the normal auricle (P> 0.05). These results indicate that the reconstructed auricle was symmetrical to the contralateral ear.Conclusion: The positioning ruler evaluated in this study is simple, easy to use, accurate, and non-invasive.Keywords: microtia, reconstructed auricle, ruler, ear

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.

This study aimed to compare the therapeutic effects of biplane skin dilator implantation with those of conventional skin dilator implantation in auricular reconstruction. A total of 137 patients with microtia who met the inclusion criteria from January 2020 to April 2021 were retrospectively selected. Sixty-three patients comprised the control group and were implanted with a skin expander using the conventional method. Seventy-four patients comprised the experimental group and were implanted with a skin expander using the biplane method. Non-parametric tests were used to compare the down-moving distance of the skin dilator between the experimental group and the control group. There was a statistically significant difference in the down-moving distance of the skin dilator between the experimental group and the control group (P P > 0.05). Moreover, there was no significant difference in the satisfaction rate of patients and their families between the experimental group and the control group (P > 0.05). In this study, the treatment effect of biplane skin dilator implantation was better than that of conventional skin dilator implantation.

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Background Sperm-associated antigen 9 (SPAG9) is closely related to the growth and metastasis of advanced prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase chemotherapy efficacy for advanced prostate cancer. Methods Oncolytic adenovirus carrying a short hairpin RNA (shRNA) targeting SPAG9 (ZD55-shSPAG9) was applied alone or in combination with docetaxel in prostate cancer cells. Cells were analyzed by cell counting kit-8, Hocehst-33258, transwell and western blot analysis. For in vivo experiments, nude mice were loaded with prostate cancer cells. Results ZD55-shSPAG9 effectively silenced the expression of SPAG9 in prostate cancer cells in vitro and in vivo. The replication of ZD55-shSPAG9 in prostate cancer cells was not affected by docetaxel, but the combined use of ZD55-shSAPAG9 and docetaxel has a better inhibitory effect on tumor growth and invasion in vitro and in vivo. Conclusions Our study showed that the combined use of ZD55-shSPAG9 and docetaxel may be a new approach to the treatment of advanced prostate cancer.

Background TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia. Objective Our goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting. Methods Case–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018. Results A total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration 480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. Conclusions These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

The etiology of epilepsy remains undefined in two-thirds of patients. Here, we identified a de novo mutation of ATP1A2 (c.2426 T>G, p.Leu809Arg), which encodes the α2 subunit of Na+/K+-ATPase, from a family with idiopathic epilepsy. This mutation caused seizures in the study patients. We generated the point mutation mouse model Atp1a2L809R, which recapitulated the epilepsy observed in the study patients. In Atp1a2L809R/WT mice, convulsions were observed and cognitive and memory function was impaired. This mutation affected the potassium binding function of the protein, disabling its ion transport ability, thereby increasing the frequency of nerve impulses. Our work revealed that ATP1A2L809R mutations cause a predisposition to epilepsy. Moreover, we first provide a point mutation mouse model for epilepsy research and drug screening.

High-field magnetic resonance imaging (MRI, 3.0T and above) offers numerous advantages for imaging the human body over lower-field strengths. However, it suffers from unwanted fast spatially-varying main (B0 ) fields caused by the susceptibility mismatch at the tissue interfaces. When this is combined with the anatomical complexity of the human body, undesirable image artifacts can become damaging as they can compromise potential image contrasts, limit the use of accelerated imaging, and interfere with clinical interpretation. Consequently, these limitations restrict the effective utilization of high-field body MRI and emphasize the need for a major improvement in B0 field homogeneity to take full advantage of the ever increased B0 field. Here we introduce a Unified shim-RF Coil (UNIC) to overcome this existing bottleneck by transcending the conventional low-efficiency, distantly located B0 shim coils. UNIC allows a shim array to be freely allotted and seamlessly integrated into a standard surface RF coil, thus maximizing both the performance of RF receive sensitivity and effective B0 shimming. We demonstrate the capacity of the UNIC approach through detailed characterization of the coil design, prototyping a body coil integrating the UNIC features, and conducting in-vivo imaging of deep organs adjacent to the lung. Our studies provide evidence that UNIC enables homogeneous B0 fields in the liver and the heart, where strong image artifacts are known to occur, and hence facilitate the acquisition of unprecedented image quality in a clinical 3.0T scanner. Further, UNIC’s design is practical as it overcomes one of the most, if not the most, critical limitations of the state-of-the-art high-field MRI with minimal changes to the current MRI hardware architecture. Accordingly, the proposed technique offers opportunities for major advancements in noninvasive imaging of deep organs with high-field imaging in a way it has not been possible thus far.

s Exosomal microRNAs (miRNAs) play a key role in cell-cell communication to regulate gene expression in target cells and have great potential as biomarkers for disease diagnosis. This paper reports an on-chip exosomal miRNA amplification and detection system for rapid analysis of exosomal miRNAs. The compact system consists of two connected flow cells for processing exosomes and detecting miRNAs, respectively. The miRNAs extracted from exosomes were quantitatively measured using the on-chip exponential amplification reaction (EXPAR) assay. The sensor chip was designed to store multiple oligonucleotide templates for the EXPAR, mix sample and reagent, and simultaneously analyze multiple exosomal miRNAs of interest. To facilitate the miRNA analysis, a portable detection instrument was built on an IoT platform using a low-cost microcontroller to execute the EXPAR assay, collect fluorescent images, and analyze amplification curves. Here, we studied the miRNA profiles carried by exosomes derived from three different phenotypes of tissue macrophages. The affordable instrument, rapid assay, multiplexed analysis, as well as disposable sensor chip, would boost the development of point-of-care liquid biopsy tests using exosomal miRNAs.

Tremendous historical and recent building vector maps are available from private surveying and mapping departments or open-source platforms such as Open Street Map (OSM). However, there invariably exist offsets between the building vectors and new remote sensing images, caused by geometric registration errors and parallax from hypsography. Consequently, these vector maps cannot be directly used as labels for the up-to-date GIS productions, as well as popular supervised machine learning. As the first work of this kind, this paper proposes an offset correction method, based on deep learning, to predict the bias between a vector building map and a new remote sensing image. The method is based on a dense regression model to predict the offsets between the image and the vector map at the pixel level, which are then processed to retrieve the offsets of each polygon. Two datasets consist of remote sensing images and biased building polygons, the WHU change detection and London datasets, are prepared to test the effectiveness of our approach. In the WHU change detection dataset, approaching 80% polygons can be correctly registered within the tolerance of three pixels, in the London dataset, more than 60% polygons can be corrected by a pre-trained model on an available open-source dataset, both of which demonstrated that our method can contribute to the GIS map updating and more efficient preparation of training samples for a deep learning model.

Background Molecular testing for oncogenic mutations in fine‐needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology. Methods To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five‐gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five‐gene diagnostic panel in differential diagnosis of thyroid nodules. Results A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine‐needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty‐nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five‐gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five‐gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules. Conclusion The five‐gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine‐needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules., Our study focuses on the feasibility and utility of a five‐gene panel containing BRAF/RAS/TERT mutation detection in the improvement of fine‐needle aspiration biopsy (FNAB) cytology in differential diagnosis of thyroid nodules in China. Our results demonstrated that BRAF/five‐gene mutations detected in FNAB samples can effectively improve the sensitivity, negative predictive value (NPV), and accuracy of FNAB cytology, while kept the specificity and positive predictive value (PPV).

IntroductionCognitive deficit is a common syndrome of methamphetamine (MA) dependence, it relates to decision-making, control ability, and social functioning. High-Intensity Interval Training (HIIT) is a training technique that requests people to work out at full intensity during a short period. A number of studies have already shown the potential effects of HIIT on cognitive roles. A number of studies have already shown the potential effects of HIIT on cognitive function. The purpose of this trial is to evaluate the cognitive effects of HIIT on the individuals of MA dependent. Methods and analysis240 individuals of MA dependent are randomly assigned to High-intensity Interval Training group (HIIT), Moderate-intensity Continuous Training group (MICT) and Control group (CON) respectively. HIIT consists of a 24-minute exercise of high-intensity interval training on a treadmill. MICT consists of a 1-hour body-mind exercise. CON remains their traditional intervention. The experimental period will be 12 months, with 3 interventions weekly for the first 6 months and follow-up for the next 6 months. All subjects will be given both physical and cognitive tests at baseline, after intervention and follow-up. The cognitive performances will be compared by a mixed-model analysis for repeated-measures.DiscussionHIIT training may reduce illicit drug cravings among individuals of MA dependent, it indicates that HIIT has better effect on cognitive functions such as memory and executive function for individuals of MA dependent.Trial Registration ChiCTR, ChiCTR2000032492, Registered on Aril 30, 2020, Prospective registration, http://www.chictr.org.cn/edit.aspx?pid=52127&htm=4.

IntroductionOlder adults have the greatest burden of asthma and poorest outcomes. The pharmacogenetics of inhaled corticosteroid (ICS) treatment response is not well studied in older adults.MethodsA genome-wide association study of ICS response was performed in asthmatics of European ancestry in Genetic Epidemiology Research on Adult Health and Aging (GERA) by fitting Cox proportional hazards regression models, followed by validation in the Mass General Brigham (MGB) Biobank and Rotterdam Study. ICS response was measured using two definitions in asthmatics on ICS treatment: (1) absence of oral corticosteroid (OCS) bursts using prescription records and (2) absence of asthma-related exacerbations using diagnosis codes. A fixed-effect meta-analysis was performed for each outcome. The validated single-nucleotide polymorphisms (SNPs) were functionally annotated to standard databases.ResultsIn 5710 subjects in GERA, 676 subjects in MGB Biobank, and 465 subjects in the Rotterdam Study, four novel SNPs on chromosome six nearPTCHD4validated across all cohorts and met genome-wide significance on meta-analysis for the OCS burst outcome. In 4541 subjects in GERA and 505 subjects in MGB Biobank, 152 SNPs with p−5were validated across these two cohorts for the asthma-related exacerbation outcome. The validated SNPs included methylation and expression quantitative trait loci forCPED1,CRADDandDSTfor the OCS burst outcome andGM2A,SNW1,CACNA1C,DPH1, andRPS10for the asthma-related exacerbation outcome.ConclusionsMultiple novel SNPs associated with ICS response were identified in older adult asthmatics. Several SNPs annotated to genes previously associated with asthma and other airway or allergic diseases, includingPTCHD4.

We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.

Purpose This observational study aimed to identify the independent risk factors for both the acquisition and mortality of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) bacteremia and further assess the in vitro antimicrobial activities of ceftazidime–avibactam (CAZ/AVI) and aztreonam–avibactam (ATM/AVI) against recent CRE bacteremic isolates. Patients and methods This observational study was conducted to reveal the risk factors and mortality rate for CP-CRE bacteremia between 2012 and 2018 and also evaluate the in vitro antimicrobial activities of CAZ/AVI and ATM/AVI against recent CRE bacteremic isolates from 2016 to 2018. Results A total of 81 non-repetitive isolates were collected from 2012 to 2018, with 67.90% (55/81) being CP-CRE. Old age (P = 0.01), transfusion [odds ratio (OR): 17.19; 95% CI: 3.15–93.72; P = 0.001], longer ICU stay (P = 0.02), cancer (OR: 15.91; 95% CI: 3.56–71.37; P < 0.001), and previous carbapenem exposure (OR: 27.86; 95% CI: 5.03–154.19; P = 0.001) were identified as independent risk factors for the acquisition of CP-CRE bacteremia compared with the ESBL bacteremia. The in vitro antimicrobial activities of CAZ/AVI and ATM/AVI against the CRE bacteremic isolates from 2016 to 2018 showed a respective susceptibility rate of 70.68% (41/58) and 100.00% (58/58). Conclusion The findings indicated that both CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination were necessary for better guiding the clinical management of CRE bacteremia: ATM/AVI probably works with both non-CP-CRE and CP-CRE bacteremia, even the most notorious double-carbapenemase producer with porin loss/deficiency, whereas CAZ/AVI works with most of the non-CP-CRE and KPC-producers in the region.

Atherosclerotic plaque rupture is an important pathophysiologic mechanism of acute coronary syndrome. Emerging microRNAs (miRNAs) have been implicated in the atherosclerotic plaque formation and macrophage autophagy during the development of atherosclerosis (AS). Hence, this study was conducted to explore the role microRNA-135b (miR-135b) in macrophages and atherosclerotic plaque in mouse models of AS. The expression of miR-135b and erythropoietin receptor (EPOR) was altered in atherosclerotic mice to clarify their effect on inflammation, cell activities of aortic tissues, and macrophage autophagy. The obtained findings unraveled that miR-135b was upregulated and EPOR was downregulated in atherosclerotic mice. Upregulated miR-135b expression promoted cell apoptosis and inflammation, along with inhibited cell proliferation and decreased macrophage autophagy. Notably, miR-135 was validated to target EPOR and activate the PI3K/Akt signaling pathway. Moreover, miR-135b inhibition attenuated inflammation, atherosclerotic plaque development, and promoted macrophage autophagy. Besides, the effect of miR-135b inhibition was reversed in response to EPOR silencing. Taken conjointly, the study revealed that inhibition of miR-135b promoted macrophage autophagy and atherosclerotic plaque stabilization in atherosclerotic mice by inactivating the PI3K/Akt signaling pathway and upregulating EPOR.

Hydrogen (H2) plays a vital role both as a reactant in petrochemical processes and as an energy carrier and storage medium. When produced from carbon-containing feed stocks, such as fossil fuels and biomass, hydrogen is typically produced as a mixture with carbon dioxide (CO2), and must be subsequently separated by the associated energy, with an invertible energy penalty. In this study, the process for the removal of carbon dioxide from CO2 - H2 mixtures by de-sublimation was analysed. This process is particularly relevant to the production of liquid hydrogen (LH2) at cryogenic temperatures, for which cooling of the H2 stream is already necessary. The solid – gas equilibrium of CO2 - H2 was studied using the Peng-Robinson equation of state which provided a wide range of operating conditions for process simulation. The de-sublimation process was compared with selected conventional separation processes, including amine-based absorption, pressure swing adsorption and membrane separation. In the scenario in which the resulting products, carbon dioxide and hydrogen, were subsequently liquefied for transportation and storage at 10 bar and −46 °C, and 1 bar and −251.8 °C, respectively. The overall energy consumption per kg of CO2 separated (MJ/kgCO2), was found to follow the order: 8.19–11.21 for monoethanolamine (MEA) absorption; 1.81–8.93 for membrane separation; 1.53–5.69 for pressure swing adsorption; and 0.81–3.35 de-sublimation process. Each process was evaluated and compared on the bases of electricity demand, cooling water usage, high-pressure steam usage, and refrigeration energy requirements. Finally, the advantages and disadvantages were discussed and the feasibility and sustainability of the processes for application in the production of liquid hydrogen were assessed.

Background Preterm birth and feeding are the most important pathogenic factors of neonatal necrotizing enterocolitis (NEC). Metabonomic has been widely used in the diagnosis and treatment of other diseases, but there is no research on the related diseases of premature infants. Compared with full-term infants, the metabolism of preterm infants has its own specificity, so it can easily lead to NEC and other digestive tract inflammatory diseases. Metabonomic may be applied to the diagnosis of preterm related diseases, such as NEC. Methods The model was established with premature infant serum samples from 19 premature infants in our hospital, which was compared with the full-term infant control group. Serum was analyzed by gas chromatography-mass spectrometry (GC-MS), coupled with the analysis of serum metabolic characteristics. The variable important in projection, P value and Pearson correlation coefficient of samples were analyzed by using SIMCA, SPSS and other multivariate statistical analysis software. Results Compared to the term infants, premature infants had significantly higher levels of luteolin, and lower levels of xylose, O-succinyl-L-homoserine and lauric acid in the serum. There were some correlations among several different metabolites and clinically related indices (albumin, total bilirubin) for premature birth related diseases. Conclusions There are metabolic alterations in the serum of premature infants, which make contribution to the diagnosis of NEC.

This study derived the analytical solutions for the deflection, bending moment and shear force of a hard roof under an arbitrary front abutment pressure for both the initial and periodic fracture problems using the elastic foundation beam model. With the assumption that the overburden pressure is constant in a small section, the roof subjected to arbitrarily distributed pressures is divided into a number of sufficiently small sections, whose closed-form solutions can be obtained easily. The proposed analytical solutions are validated by comparisons with those calculated using a model reported in the literature, in which the overburden pressure is assumed to follow a normal distribution. The parametric studies on the foundation stiffness, front abutment pressure and support resistance show that: (1) with the decrease of elastic foundation stiffness, the deflection and the maximum bending moment significantly increase, and the shear force significantly changes in the unmined region; (2) as the peak point position moves inside the coal wall, the deflection of the goaf roof, as well as the maximum bending moment and shear force, obviously decrease; (3) with the increase of support resistance, the maximum bending moment and deflection significantly decrease, and the shear force significant decreases in the hydraulic support region; (4) when the coal seam is soft and peak position of the front abutment pressure is near the coal wall, initial fracture occurs at the midspan; otherwise, it occurs inside the coal wall. For the periodic fracture condition, the fracture position is closer to the coal wall when the coal seam is harder, and the fracture length increases when the peak position of front abutment pressure moves inside the coal wall.

Milk fat globule-EGF factor 8 (MFGE8) has been reported to play various roles in acute injury and inflammation response. However, the role of MFGE8 in liver injury is poorly investigated. The present research was designed to clarify the expression and function of MFGE8 in carbon tetrachloride (CCl4 )-induced liver injury. Using serum cytokine arrays, we selected a promising cytokine MFGE8 as the candidate in the process of hepatitis-fibrosis-hepatocellular carcinoma (HCC) progression, based on the elevated expression in both hepatic fibrosis and HCC models. We validated the increased expression of MFGE8 in liver tissues and serum samples of acute and chronic CCl4 -induced mice. Immunohistochemistry staining of mouse liver tissues indicated that elevated MFGE8 expression was mainly derived from the injured hepatocytes. In addition, MFGE8 expression in the supernatant of primary hepatocytes was accumulated with prolongation of culture time, and CCl4 treatment further increased the expression of MFGE8. Moreover, a strong correlation between serum MFGE8 expression and liver transaminase activities suggested that MFGE8 may be a novel candidate in liver injury. Intriguingly, mice pretreated with MFGE8 were protected from CCl4 -induced liver injury through antiapoptosis role in the early stage and proproliferation role in the late stage. MFGE8 reduced apoptosis by inhibiting the activation of IRE1α/ASK1/JNK pathway and promoted proliferation by phosphorylation of ERK and AKT. Moreover, serum MFGE8 expression was increased in hepatitis patients while decreased in liver cirrhosis patients. All the results suggest MFGE8 as a novel marker and promising therapeutic agent of liver injury.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

Cycloidal gears play an important role in the performance of rotate vector (RV) reducers. In this article, numerical analysis of mixed elastohydrodynamic lubrication (EHL) is applied to establish a...

Background and Objective Due to the synergistic effects of drugs, drug combination is one of the effective approaches for treating complex diseases. However, the identification of drug combinations by dose-response methods is still costly. It is promising to develop supervised learning-based approaches to predict potential drug combinations on a large scale. Nevertheless, these approaches have the inadequate utilization of heterogeneous features, which causes the loss of information useful to classification. Moreover, they have an intrinsic bias, because they assume unknown drug pairs as non-combinations, of which some could be real drug combinations in practice. Methods To address above issues, this work first designs a two-layer multiple classifier system (TLMCS) to effectively integrate heterogeneous features involving anatomical therapeutic chemical codes of drugs, drug-drug interactions, drug-target interactions, gene ontology of drug targets, and side effects. To avoid the bias caused by labelling unknown samples as negative, it then utilizes the one-class support vector machines, (which requires no negative instance and only labels approved drug combinations as positive instances), as the member classifiers in TLMCS. Last, both a 10-fold cross validation (10-CV) and a novel prediction are performed to validate the performance of TLMCS. Results The comparison with three state-of-the-art approaches under 10-CV exhibits the superiority of TLMCS, which achieves the area under the receiver operating characteristic curve = 0.824 and the area under the precision-recall curve = 0.372. Moreover, the experiment under the novel prediction demonstrates its ability, where 9 out of the top-20 predicted combinative drug pairs are validated by checking the published literature. Furthermore, for each of the newly-validated drug combinations, this work analyses the combining mode of the member drugs and investigates their relationship in terms of drug targeting pathways. Conclusions The proposed TLMCS provides an effective framework to integrate those heterogeneous features and is trained by only positive samples such that the bias of taking unknown drug pairs as negative samples can be avoided. Furthermore, its results in the novel prediction reveal five types of drug combinations and three types of drug relationships in terms of pathways.

The application of the convolutional neural network has shown to greatly improve the accuracy of building extraction from remote sensing imagery. In this paper, we created and made open a high-quality multisource data set for building detection, evaluated the accuracy obtained in most recent studies on the data set, demonstrated the use of our data set, and proposed a Siamese fully convolutional network model that obtained better segmentation accuracy. The building data set that we created contains not only aerial images but also satellite images covering 1000 km2 with both raster labels and vector maps. The accuracy of applying the same methodology to our aerial data set outperformed several other open building data sets. On the aerial data set, we gave a thorough evaluation and comparison of most recent deep learning-based methods, and proposed a Siamese U-Net with shared weights in two branches, and original images and their down-sampled counterparts as inputs, which significantly improves the segmentation accuracy, especially for large buildings. For multisource building extraction, the generalization ability is further evaluated and extended by applying a radiometric augmentation strategy to transfer pretrained models on the aerial data set to the satellite data set. The designed experiments indicate our data set is accurate and can serve multiple purposes including building instance segmentation and change detection; our result shows the Siamese U-Net outperforms current building extraction methods and could provide valuable reference.

Increasing evidence suggests the consensus that direct in vivo application of induced pluripotent stem cells (iPSCs) is infeasible may not be true. Methods: Teratoma formation and fate were examined in 53 normal and disease conditions involving brain, lung, liver, kidney, islet, skin, hind limb, and arteries. Results: Using classic teratoma generation assays, which require iPSCs to be congregated and confined, all mouse, human, and individualized autologous monkey iPSCs tested formed teratoma, while iPSC-derived cells did not. Intravenously or topically-disseminated iPSCs did not form teratomas with doses up to 2.5×108 iPSCs/kg and observation times up to 18 months, regardless of host tissue type; autologous, syngeneic, or immune-deficient host animals; presence or absence of disease; disease type; iPSC induction method; commercial or self-induced iPSCs; mouse, human, or monkey iPSCs; frequency of delivery; and sex. Matrigel-confined, but not PBS-suspended, syngeneic iPSCs delivered into the peritoneal cavity or renal capsule formed teratomas. Intravenously administered iPSCs were therapeutic with a dose as low as 5×106/kg and some iPSCs differentiated into somatic cells in injured organs. Disseminated iPSCs trafficked into injured tissue and survived significantly longer in injured than uninjured organs. In disease-free animals, no intravenously administered cell differentiated into an unwanted long-lasting cell or survived as a quiescent stem cell. In coculture, the stem cell medium and dominant cell-type status were critical for iPSCs to form cell masses. Conclusion: Teratoma can be easily and completely avoided by disseminating the cells. Direct in vivo iPSC application is feasible and can be safe.

This paper describes a tape nanolithography method for the rapid and economical manufacturing of flexible, wearable nanophotonic devices. This method involves the soft lithography of a donor substrate with air-void nanopatterns, subsequent deposition of materials onto the substrate surface, followed by direct taping and peeling of the deposited materials by an adhesive tape. Without using any sophisticated techniques, the nanopatterns, which are preformed on the surface of the donor substrate, automatically emerge in the deposited materials. The nanopatterns can then be transferred to the tape surface. By leveraging the works of adhesion at the interfaces of the donor substrate-deposited material-tape assembly, this method not only demonstrates sub-hundred-nanometer resolution in the transferred nanopatterns on an area of multiple square inches but also exhibits high versatility and flexibility for configuring the shapes, dimensions, and material compositions of tape-supported nanopatterns to tune their optical properties. After the tape transfer, the materials that remain at the bottom of the air-void nanopatterns on the donor substrate exhibit shapes complementary to the transferred nanopatterns on the tape surface but maintain the same composition, thus also acting as functional nanophotonic structures. Using tape nanolithography, we demonstrate several tape-supported plasmonic, dielectric, and metallo-dielectric nanostructures, as well as several devices such as refractive index sensors, conformable plasmonic surfaces, and Fabry-Perot cavity resonators. Further, we demonstrate tape nanolithography-assisted manufacturing of a standalone plasmonic nanohole film and its transfer to unconventional substrates such as a cleaved facet and the curved side of an optical fiber.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal protein in low-density lipoprotein cholesterol metabolism, has been validated to be an established target for cardiovascular (CV) risk reduction. Nevertheless, prospective studies concerning the associations between circulating PCSK9 and the risk of CV events and mortality have yielded, so far, inconsistent results. Herein, we conducted a meta-analysis to evaluate the association systemically.Methods: Pertinent studies were identified from PubMed, EMBASE, and Cochrane Library database through July 2020. Longitudinal studies investigating the value of circulating PCSK9 for predicting major adverse cardiovascular events (MACEs) or stroke or all-cause mortally with risk estimates and 95% confidence intervals (CI) were included in the analyses. Dose-response meta-analysis was also applied to evaluate circulating PCSK9 and risk of MACEs in this study.Results: A total of 22 eligible cohorts comprising 28,319 participants from 20 eligible articles were finally included in the study. The pooled relative risk (RR) of MACEs for one standard deviation increase in baseline PCSK9 was 1.120 (95% CI, 1.056–1.189). When categorizing subjects into tertiles, the pooled RR for the highest tertile of baseline PCSK9 was 1.252 (95% CI, 1.104–1.420) compared with the lowest category. This positive association between PCSK9 level and risk of MACEs persisted in sensitivity and most of the subgroup analyses. Twelve studies were included in dose-response meta-analysis, and a linear association between PCSK9 concentration and risk of MACEs was observed (x2 test for non-linearity = 0.31, P non-linearity = 0.575). No significant correlation was found either on stroke or all-cause mortality.Conclusion: This meta-analysis added further evidence that high circulating PCSK9 concentration significantly associated with increased risk of MACEs, and a linear dose-response association was observed. However, available data did not suggest significant association either on stroke or all-cause mortality. Additional well-designed studies are warranted to further investigate the correlations between PCSK9 concentration and stroke and mortality.

Hui Yang,* Lan Liu,* Gai Li, Yinchen Chen, Dong Jiang, Wei Wang, Tianyuan Wang, Jinshan Sun, Jianfang Che, Dongmei Gu, Meng Lu, Aiping Wang Department of Endocrinology, The Air Force Hospital from Eastern Theater of PLA, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aiping Wang; Meng LuDepartment of Endocrinology, The Air Force Hospital from Eastern Theater of PLA, 1 Malujie Road, Nanjing 210029, People’s Republic of ChinaTel +86-25-80865162Email wap454hospital@163.com; lumeng365@hotmail.comAim: To explore the growth-promoting effect of vacuum sealing drainage (VSD) during the healing processes of diabetic foot ulcers (DFUs).Methods: From November 2018 to December 2019, 38 patients with unilateral DFUs were enrolled in this retrospective study. All patients were divided into two groups according to the use of VSD or not: the VSD group (n=20) and the control group (n=18). The following parameters were used to evaluate the healing process: changes in the mean areas of the ulcers; healing rate (HR); epithelial hyperplasia and angiogenesis as determined by hematoxylin-eosin staining (HE staining); and expression of CD34, CD68 and VEGF as assessed through immunohistochemistry. Perioperative side effects and complications were also recorded.Results: All patients received follow-up and eventually healed. The mean area of wounds was reduced in the VSD group compared to the control group (1.75± 0.64 cm2 vs 0.88± 0.54 cm2, P=0.031). The mean HR of the ulcers in the VSD group was significantly higher than that in the control group (35.23± 2.87% vs 28.78± 1.09%, P=0.017). HE staining showed that the amount of epithelial hyperplasia and angiogenesis increased significantly after VSD, and the immunohistochemistry results showed that the expression of CD34, CD68 and VEGF increased significantly in the VSD group.Conclusion: VSD could significantly accelerate the wound healing process, probably by enhancing the inflammatory response and promoting granulation and angiogenesis in DFUs.Keywords: vacuum sealing drainage, diabetic foot ulcers, wound healing, CD34, CD68, VEGF

Background and Purpose: Hematoma expansion is closely associated with adverse functional outcomes in patients with intracerebral hemorrhage (ICH). Prediction of hematoma expansion would therefore be of great clinical significance. We therefore attempted to predict hematoma expansion using a dual-modal machine learning (ML) strategy which combines information from non-contrast computed tomography (NCCT) images and multiple clinical variables. Method: We retrospectively identified 140 ICH patients (57 with hematoma expansion) with 5,616 NCCT images of hematoma (2,635 with hematoma expansion) and 10 clinical variables. The dual-modal ML strategy consists of two steps. The first step is to derive a mono-modal predictor from a deep convolutional neural network (DCNN) using solely NCCT images. The second step is to achieve a dual-modal predictor by combining the mono-modal predictor with 10 clinical variables to predict hematoma growth using a multi-layer perception (MLP) network. Result: For the mono-modal predictor, the best performance was merely 69.5% in accuracy with solely the NCCT images, whereas the dual-modal predictor could boost the accuracy greatly to be 86.5% by combining clinical variables. Conclusion: To our knowledge, this is the best performance from using ML to predict hematoma expansion. It could be potentially useful as a screening tool for high-risk patients with ICH, though further clinical tests would be necessary to show its performance on a larger cohort of patients.