Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats
. ...Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans
. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
Breast cancer is an all too common disease in women, making how to effectively predict it an active research problem. A number of statistical and machine learning techniques have been employed to ...develop various breast cancer prediction models. Among them, support vector machines (SVM) have been shown to outperform many related techniques. To construct the SVM classifier, it is first necessary to decide the kernel function, and different kernel functions can result in different prediction performance. However, there have been very few studies focused on examining the prediction performances of SVM based on different kernel functions. Moreover, it is unknown whether SVM classifier ensembles which have been proposed to improve the performance of single classifiers can outperform single SVM classifiers in terms of breast cancer prediction. Therefore, the aim of this paper is to fully assess the prediction performance of SVM and SVM ensembles over small and large scale breast cancer datasets. The classification accuracy, ROC, F-measure, and computational times of training SVM and SVM ensembles are compared. The experimental results show that linear kernel based SVM ensembles based on the bagging method and RBF kernel based SVM ensembles with the boosting method can be the better choices for a small scale dataset, where feature selection should be performed in the data pre-processing stage. For a large scale dataset, RBF kernel based SVM ensembles based on boosting perform better than the other classifiers.
The liver plays a pivotal role in mammalian aging. However, the mechanisms underlying liver aging remain unclear. Cisd2 is a pro‐longevity gene in mice. Cisd2 mediates lifespan and healthspan via ...regulation of calcium homeostasis and mitochondrial functioning. Intriguingly, the protein level of Cisd2 is significantly decreased by about 50% in the livers of old male mice. This down‐regulation of Cisd2 may result in the aging liver exhibiting non‐alcoholic fatty liver disease (NAFLD) phenotype. Here, we use Cisd2 transgenic mice to investigate whether maintaining Cisd2 protein at a persistently high level is able to slow down liver aging. Our study identifies four major discoveries. Firstly, that Cisd2 expression attenuates age‐related dysregulation of lipid metabolism and other pathological abnormalities. Secondly, revealed by RNA sequencing analysis, the livers of old male mice undergo extensive transcriptomic alterations, and these are associated with steatosis, hepatitis, fibrosis, and xenobiotic detoxification. Intriguingly, a youthful transcriptomic profile, like that of young 3‐month‐old mice, was found in old Cisd2 transgenic male mice at 26 months old. Thirdly, Cisd2 suppresses the age‐associated dysregulation of various transcription regulators (Nrf2, IL‐6, and Hnf4a), which keeps the transcriptional network in a normal pattern. Finally, a high level of Cisd2 protein protects the liver from oxidative stress, and this is associated with a reduction in mitochondrial DNA deletions. These findings demonstrate that Cisd2 is a promising target for the development of therapeutic agents that, by bringing about an effective enhancement of Cisd2 expression, will slow down liver aging.
The protein level of CDGSH iron‐sulfur domain‐containing protein 2 (Cisd2) is decreased by about 50% in the aged livers of old mice. RNA sequencing and histopathological analyses reveal that in the Cisd2 transgenic mice, a persistently high level of Cisd2 slows down liver aging via attenuating oxidative stress and mitochondrial DNA deletion, as well as preserving a youthful transcriptomic profile, thereby protecting the liver against age‐associated structural injury and functional decline.
Obesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status ...modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community. We examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, less than or equal to25 kg/m.sup.2 lean; high, >25 kg/m.sup.2 obese) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, <45 g/L malnourished; high, greater than or equal to45 g/L well-nourished), and secondarily by the prognostic nutritional index (PNI) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Cox proportional hazard models were used to examine a 1-year composite outcome of hospitalization for HF or all-cause mortality while adjusting for age, sex, and other clinical confounders. Our community-based cohort consisted of 2,096 (39.0%) lean-well-nourished (low BMI, high SA), 1,369 (25.8%) obese-well-nourished (high BMI, high SA), 1,154 (21.8%) lean-malnourished (low BMI, low SA), and 681 (12.8%) obese-malnourished (high BMI, low SA) individuals. Obese-malnourished participants were on average older (54.5 ± 11.4 years) and more often women (41%), with a higher mean waist circumference (91.7 ± 8.8 cm), the highest percentage of body fat (32%), and the highest prevalence of hypertension (32%), diabetes (12%), and history of cardiovascular disease (11%), compared to all other subgroups (all p < 0.001). N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were substantially increased in the malnourished (versus well-nourished) groups, to a similar extent in lean (70.7 ± 177.3 versus 36.8 ± 40.4 pg/mL) and obese (73.1 ± 216.8 versus 33.2 ± 40.8 pg/mL) (p < 0.001 in both) participants. The obese-malnourished (high BMI, low SA) group also had greater left ventricular remodeling (left ventricular mass index, 44.2 ± 1.52 versus 33.8 ± 8.28 gm/m.sup.2 ; relative wall thickness 0.39 ± 0.05 versus 0.38 ± 0.06) and worse diastolic function (TDI-e' 7.97 ± 2.16 versus 9.87 ± 2.47 cm/s; E/e' 9.19 ± 3.01 versus 7.36 ± 2.31; left atrial volume index 19.5 ± 7.66 versus 14.9 ± 5.49 mL/m.sup.2) compared to the lean-well-nourished (low BMI, high SA) group, as well as all other subgroups (p < 0.001 for all). Over a median 3.6 years (interquartile range 2.5 to 4.8 years) of follow-up, the obese-malnourished group had the highest multivariable-adjusted risk of the composite outcome (hazard ratio HR 2.49, 95% CI 1.43 to 4.34, p = 0.001), followed by the lean-malnourished (HR 1.78, 95% CI 1.04 to 3.04, p = 0.034) and obese-well-nourished (HR 1.41, 95% CI 0.77 to 2.58, p = 0.27) groups (with lean-well-nourished group as reference). Results were similar when indexed by other anthropometric indices (waist circumference and body fat) and other measures of nutritional status (PNI and GLIM criteria). Potential selection bias and residual confounding were the main limitations of the study. In our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome.
The effect of secondary phases of AZ31B and WE43-T5 Mg alloys on corrosion behaviors was studied in 3.5 wt% NaCl solution. Electrochemical and microstructural characterizations revealed that compared ...to AZ31B, WE43-T5 suffered less hydrogen evolution without corrosion film breakdown. The corrosion film of both AZ31B and WE43-T5 was mainly Mg oxide/hydroxide. The TEM analysis revealed that Y and Nd oxide/hydroxide enrichment in the corrosion film/WE43-T5 interface resulted from the corrosion of the strengthening nanoparticles. Conversely, the Al-rich layer was not detected at the corrosion film/AZ31B interface, and the Al-Mn secondary phases caused severe galvanic corrosion.
•WE43-T5 had less evolved hydrogen without corrosion film breakdown.•Galvanic corrosion prevailed at Al-Mn particle and α-Mg of AZ31B.•Galvanic corrosion was very mild at Mg24Y5 and α-Mg of WE43-T5.•Y and Nd species were enriched in corrosion film/WE43-T5 interface.•Y, Nd oxide/hydroxide played a major role in the corrosion resistance of WE43-T5.
Diabetic ketoacidosis (DKA) is associated with dehydration and which can cause acute kidney injury (AKI). The proportion of AKI in children and adolescents with DKA has not been reported in East ...Asian population. This study aimed to identify the prevalence of AKI and to determine whether there is an association between AKI severity and recovery time from metabolic acidosis in children and adolescents with DKA. Medical records of children and adolescents (aged 1.5 times the calculated expected baseline creatinine level. Patients were divided into three groups based on AKI severity: no AKI, mild AKI, and severe AKI. In total, 170 (56.5%) patients with DKA presented AKI (mild AKI, 116 38.5%; severe AKI, 54 18.0%). Heart rate and laboratory parameters related to dehydration, such as corrected sodium level and blood urea nitrogen, were strongly associated with AKI development (P<0.01). Blood pH, plasma glucose, and potassium levels were also associated with AKI. A negative correlation with borderline significance between the estimated glomerular filtration rate (eGFR) and recovery time from metabolic acidosis was observed in the severe AKI group. AKI was highly prevalent in children and adolescents with DKA. An association between AKI and biomarkers indicating dehydration was noted. The recovery time from metabolic acidosis following treatment may be longer in children with a decreased eGFR who present with severe AKI. AKI is a common complication in children with DKA.
Geologically, La Paz City is located in an unstable area. During the history of La Paz city, many landslides have destroyed houses and valuable infrastructures. In the last decades, time series ...Interferometric Synthetic Aperture Radar (InSAR) technologies have demonstrated a great capacity for detecting slow ground displacement, achieving an accuracy of millimetre-level. In order to have a better landslide monitoring of La Paz city, in this study, the Sentinel-1 SAR images have been processed by Persistent Scatterer Interferometry (PSI) and the Small Baseline Subset (SBAS) techniques. The time span of the datasets is from March 2015 to August 2016. Both ascending and descending Synthetic Aperture Radar (SAR) images have been processed to obtain the line of sight (LOS) ground velocity, and then the results have been combined to estimate the up-down and east-west displacement. Several active movement areas have been identified, showing a surface velocity up to 158 mm year
−1
westward and 49 mm year
−1
eastward. Furthermore, two important findings have been discovered. First, the InSAR result has detected movement in Auquisamaa hill before the area collapsed (15 February 2017), where five houses are buried. Second, the InSAR result has identified that there are still some unstable sites in Callapa area, where a mega-landslide has destroyed more than a thousand of houses in February 2011. In conclusion, we have verified that the InSAR technology could be a very useful tool to help La Paz public institutions for a better management of urban planning, landslide areas delimitation and landslide risk mitigation.
Properly cut sheets can be converted into complex 3D structures by three basic operations including folding, bending, and pasting to render new functions. Folding and bending are extensively employed ...in crumpling, origami, and pop‐up fabrications for 3D structures. Pasting joins different parts of a material together, and can create new geometries that are fundamentally unattainable by folding and bending. However, it has been much less explored, likely due to limited choice of weldable thin film materials and residue‐free glues. Here it is shown that graphene oxide (GO) paper is one such suitable material. Stacked GO sheets can be readily loosened up and even redispersed in water, which upon drying, restack to form solid structures. Therefore, water can be utilized to heal local damage, glue separated pieces, and release internal stress in bent GO papers to fix their shapes. Complex and dynamic 3D GO architectures can thus be fabricated by a cut‐and‐paste approach, which is also applicable to GO‐based hybrid with carbon nanotubes or clay sheets.
Water is found to be capable of healing damage in graphene oxide (GO) paper, connecting separated pieces, and releasing stress in strained GO structures to fix their shapes, which inspires a cut‐and‐paste approach for fabricating complex and dynamic 3D GO‐based architectures that are fundamentally unattainable by folding‐ and bending‐based approaches.
Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic ...T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio OR, 1.50; 95% confidence interval CI, 1.21-1.84; corrected P value Pc < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.
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