To develop and validate a radiomics model for evaluating pathologic complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC).
We enrolled 222 ...patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2,252 radiomic features were extracted from each patient before and after treatment imaging. The two-sample
test and the least absolute shrinkage and selection operator regression were used for feature selection, whereupon a radiomics signature was built with support vector machines. Multivariable logistic regression analysis was then used to develop a radiomics model incorporating the radiomics signature and independent clinicopathologic risk factors. The performance of the radiomics model was assessed by its calibration, discrimination, and clinical usefulness with independent validation.
The radiomics signature comprised 30 selected features and showed good discrimination performance in both the primary and validation cohorts. The individualized radiomics model, which incorporated the radiomics signature and tumor length, also showed good discrimination, with an area under the receiver operating characteristic curve of 0.9756 (95% confidence interval, 0.9185-0.9711) in the validation cohort, and good calibration. Decision curve analysis confirmed the clinical utility of the radiomics model.
Using pre- and posttreatment MRI data, we developed a radiomics model with excellent performance for individualized, noninvasive prediction of pCR. This model may be used to identify LARC patients who can omit surgery after chemoradiotherapy.
.
Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought ...an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.
Display omitted
•Human ACE2 knockin mice were generated by using CRISPR/Cas9 technology•SARS-CoV-2 leads to robust replication in lung, trachea, and brain•SARS-CoV-2 causes interstitial pneumonia and elevated cytokine in aged hACE2 mice•High dose of SARS-CoV-2 can establish infection via intragastric route in hACE2 mice
The COVID-19 pandemic has brought an urgent need for small animal models. Here, Sun et al. established an ACE2 humanized mouse by CRISPR/Cas9 knockin technology. These hACE2 mice are susceptible to SARS-CoV-2 infection upon intranasal inoculation, and the resulting pulmonary infection and pathological changes resemble those observed in COVID-19 patients.
Direct methanol fuel cells (DMFCs) are among the most promising portable power supplies because of their unique advantages, including high energy density/mobility of liquid fuels, low working ...temperature, and low emission of pollutants. Various metal‐based anode catalysts have been extensively studied and utilized for the essential methanol oxidation reaction (MOR) due to their superior electrocatalytic performance. At present, especially with the rapid advance of nanotechnology, enormous efforts have been exerted to further enhance the catalytic performance and minimize the use of precious metals. Constructing multicomponent metal‐based nanocatalysts with precisely designed structures can achieve this goal by providing highly tunable compositional and structural characteristics, which is promising for the modification and optimization of their related electrochemical properties. The recent advances of metal‐based electrocatalytic materials with rationally designed nanostructures and chemistries for MOR in DMFCs are highlighted and summarized herein. The effects of the well‐defined nanoarchitectures on the improved electrochemical properties of the catalysts are illustrated. Finally, conclusive perspectives are provided on the opportunities and challenges for further refining the nanostructure of metal‐based catalysts and improving electrocatalytic performance, as well as the commercial viability.
Efficient catalysts are critical for the electrocatalytic oxidation reaction of methanol. Metal‐based anode catalysts with well‐defined nanoarchitectures and optimal chemical compositions can provide superior performance with lower costs. The possible effects, challenges, and future development are elaborately discussed to shed light on the further design of metal‐based anode catalysts for the methanol electro‐oxidation reaction, leading to a renewable energy supply future.
The ongoing worldwide SARS-CoV-2 epidemic clearly has a tremendous influence on public health. Molecular detection based on oral swabs was used for confirmation of SARS-CoV-2 infection. However, high ...false negative rates were reported. We describe here the development of a point-of-care (POC) serological assay for the detection of IgG antibody against SARS-CoV-2. The principle of a lateral flow immunoassay strip (LFIAs) consists of fixing SARS-CoV-2 nucleocapsid protein to the surface of the strip and coupling anti-human IgG with colloidal gold nanoparticles (Au NPs). A series of parameters of this method were optimized, including the concentration of coating antigen, BSA blocking concentration and pH value for conjugation. The entire detection process took 15-20 min with a volume of 80 μL of the analyte solution containing 10 μL of serum and 70 μL sample diluent. The performance of the established assay was evaluated using serum samples of the clinically diagnosed cases of Coronavirus Disease 2019 (COVID-19). Our results indicated that the LFIAs for SARS-CoV-2 had satisfactory stability and reproducibility. As a result, our fast and easy LFIAs could provide a preliminary test result for physicians to make the correct diagnosis of SARS-CoV-2 infections along with alternative testing methods and clinical findings, as well as seroprevalence determination, especially in low-resource countries.
Last year, the novel coronavirus
disease (COVID-19) emerged in
Wuhan, and it has rapidly spread to many other countries and regions.
COVID-19 exhibits a strong human-to-human transmission infectivity
...and could cause acute respiratory diseases. Asymptomatic carriers
are able to infect other healthy persons, and this poses a challenge
for public health; the World Health Organization (WHO) has already
announced COVID-19 as a global pandemic. Nucleic acid testing, considered
as the current primary method for diagnosing COVID-19, might lead
to false negatives and is difficult to be applied for every suspected
patient because of the existence of asymptomatic carriers. Meanwhile,
detecting specific antibodies in blood, such as the IgM antibody,
against the SARS-CoV-2 virus is another choice for COVID-19 diagnosis,
as it is widely accepted that IgM is an important indicator in the
acute infection period. In this study, a colloidal gold nanoparticle-based
lateral-flow (AuNP-LF) assay was developed to achieve rapid diagnosis
and on-site detection of the IgM antibody against the SARS-CoV-2 virus
through the indirect immunochromatography method. For preparing AuNP-LF
strips, the SARS-CoV-2 nucleoprotein (SARS-CoV-2 NP) was coated on
an analytical membrane for sample capture, and antihuman IgM was conjugated
with AuNPs to form the detecting reporter. Optimization of AuNP-LF
assay was carried out by altering the pH value and the amount of antihuman
IgM. The performance of AuNP-LF assay was evaluated by testing serum
samples of COVID-19 patients and normal humans. The results were compared
with the real-time polymerase chain reaction. The sensitivity and
specificity of AuNP-LF assay were determined to be 100 and 93.3%,
respectively, and an almost perfect agreement was exhibited by Kappa
statistics (κ coefficient = 0.872). AuNP-LF assay showed outstanding
selectivity in the detection of IgM against the SARS-CoV-2 virus with
no interference from other viruses such as severe fever with thrombocytopenia
syndrome virus (SFTSV) and dengue virus (DFV). AuNP-LF assay was able
to achieve results within 15 min and needed only 10–20 μL
serum for each test. As a whole, in the light of its advantages such
as excellent specificity and stability, easy operation, low cost,
and being less time-consuming, AuNP-LF assay is a feasible method
for the diagnosis of COVID-19 in primary hospitals and laboratories,
especially in emergency situations in which numerous samples need
to be tested on time.
Background
Diffusion weighted imaging (DWI) at multiple b‐values has been used to predict the pathological complete response (pCR) to neoadjuvant chemoradiotherapy for locally advanced rectal cancer. ...Non‐Gaussian models fit the signal decay of diffusion by several physical values from different approaches of approximation.
Purpose
To develop a deep learning method to analyze DWI data scanned at multiple b‐values independent on Gaussian or non‐Gaussian models and to apply to a rectal cancer neoadjuvant chemoradiotherapy model.
Study Type
Retrospective.
Population
A total of 472 participants (age: 56.6 ± 10.5 years; 298 males and 174 females) with locally advanced adenocarcinoma were enrolled and chronologically divided into a training group (n = 200; 42 pCR/158 non‐pCR), a validation group (n = 72; 11 pCR/61 non‐pCR) and a test group (n = 200; 44 pCR/156 non‐pCR).
Field Strength/Sequence
A 3.0 T MRI scanner. DWI with a single‐shot spin echo‐planar imaging pulse sequence at 12 b‐values (0, 20, 50, 100, 200, 400, 600, 800, 1000, 1200, 1400, and 1600 sec/mm2).
Assessment
DWI signals from manually delineated tumor region were converted into a signature‐like picture by concatenating all histograms from different b‐values. Pathological results (pCR/non‐pCR) were used as the ground truth for deep learning. Gaussian and non‐Gaussian methods were used for comparison.
Statistical Tests
Analysis of variance for age; Chi‐square for gender and pCR/non‐pCR; area under the receiver operating characteristic (ROC) curve (AUC); DeLong test for AUC. P < 0.05 for significant difference.
Results
The AUC in the test group is 0.924 (95% CI: 0.866–0.983) for the signature‐like pictures converted from 35 bins, and it is 0.931 (95% CI: 0.884–0.979) for the signature‐like pictures converted from 70 bins, which is significantly (Z = 3.258, P < 0.05) larger than Dapp, the best predictor in non‐Gaussian methods with AUC = 0.773 (95% CI: 0.682–0.865).
Data Conclusion
The proposed signature‐like pictures provide more accurate pretreatment prediction of the response to neoadjuvant chemoradiotherapy than the fitted methods for locally advanced rectal cancer.
Evidence Level
3
Technical Efficacy
Stage 2
The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI ...symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.
COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.
Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m
A methylation and changed binding capacity with ACE2.
We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
Hypoxia contributes to the initiation and progression of glioblastoma by regulating a cohort of genes called hypoxia-regulated genes (HRGs) which form a complex molecular interacting network ...(HRG-MINW). Transcription factors (TFs) often play central roles for MINW. The key TFs for hypoxia induced reactions were explored using proteomic analysis to identify a set of hypoxia-regulated proteins (HRPs) in GBM cells. Next, systematic TF analysis identified CEBPD as a top TF that regulates the greatest number of HRPs and HRGs. Clinical sample and public database analysis revealed that CEBPD is significantly up-regulated in GBM, high levels of CEBPD predict poor prognosis. In addition, CEBPD is highly expressed in hypoxic condition both in GBM tissue and cell lines. For molecular mechanisms, HIF1α and HIF2α can activate the CEBPD promotor. In vitro and in vivo experiments demonstrated that CEBPD knockdown impaired the invasion and growth capacity of GBM cells, especially in hypoxia condition. Next, proteomic analysis identified that CEBPD target proteins are mainly involved in the EGFR/PI3K pathway and extracellular matrix (ECM) functions. WB assays revealed that CEBPD significantly positively regulated EGFR/PI3K pathway. Chromatin immunoprecipitation (ChIP) qPCR/Seq analysis and Luciferase reporter assay demonstrated that CEBPD binds and activates the promotor of a key ECM protein FN1 (fibronectin). In addition, the interactions of FN1 and its integrin receptors are necessary for CEBPD-induced EGFR/PI3K activation by promoting EGFR phosphorylation. Furthermore, GBM sample analysis in the database corroborated that CEBPD is positively correlated with the pathway activities of EGFR/PI3K and HIF1α, especially in highly hypoxic samples. At last, HRPs are also enriched in ECM proteins, indicating that ECM activities are important components of hypoxia induced responses in GBM. In conclusion, CEPBD plays important regulatory roles in the GBM HRG-MINW as a key TF, which activates the EGFR/PI3K pathway through ECM, especially FN1, mediated EGFR phosphorylation.
Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for ...grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.
Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western ...dietary patterns. VC aggravates dietary fatty acid‐induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 μM) on hepatic steatosis of high‐fat diet (HFD)‐fed mice and palmitic acid (PA, 100 μM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single‐exposure groups (HFD group, low‐dose VC group, and high‐dose VC group). Moreover, VC enhanced HFD‐induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element‐binding protein 1 (SREBP‐1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD‐fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis‐related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.
Hepatic steatosis is a high‐risk disease for VC‐exposed workers, but animal studies have found that low concentrations of VC cannot cause hepatic steatosis. HFD is the most relevant factor for hepatic steatosis in VC‐exposed workers. Therefore, it is very important to study the mechanism of hepatic steatosis caused by VC combined with HFD. We found that VC combined with HFD has an additive effect on inducing hepatic steatosis, which may cause hepatic steatosis by promoting OS and ERS.
PDF
