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.
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Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier K+ current (IK1) is believed to be an important regulator of reentrant-spiral ...dynamics and a major component of AF-related electrical remodeling. MicroRNA-26 (miR-26) is predicted to target the gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial samples from AF animals and patients and this downregulation was accompanied by upregulation of IK1/KIR2.1 protein. miR-26 overexpression suppressed expression of KCNJ2/KIR2.1. In contrast, miR-26 knockdown, inhibition, or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-26 target. Knockdown of endogenous miR-26 promoted AF in mice, whereas adenovirus-mediated expression of miR-26 reduced AF vulnerability. Kcnj2-specific miR-masks eliminated miR-26-mediated reductions in Kcnj2, abolishing miR-26's protective effects, while coinjection of a Kcnj2-specific miR-mimic prevented miR-26 knockdown-associated AF in mice. Nuclear factor of activated T cells (NFAT), a known actor in AF-associated remodeling, was found to negatively regulate miR-26 transcription. Our results demonstrate that miR-26 controls the expression of KCNJ2 and suggest that this downregulation may promote AF.
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.
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•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.
Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, ...yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca
-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2
mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.
Evolutionary feature selection (FS) methods face the challenge of "curse of dimensionality" when dealing with high-dimensional data. Focusing on this challenge, this article studies a variable-size ...cooperative coevolutionary particle swarm optimization algorithm (VS-CCPSO) for FS. The proposed algorithm employs the idea of "divide and conquer" in cooperative coevolutionary approach, but several new developed problem-guided operators/strategies make it more suitable for FS problems. First, a space division strategy based on the feature importance is presented, which can classify relevant features into the same subspace with a low computational cost. Following that, an adaptive adjustment mechanism of subswarm size is developed to maintain an appropriate size for each subswarm, with the purpose of saving computational cost on evaluating particles. Moreover, a particle deletion strategy based on fitness-guided binary clustering, and a particle generation strategy based on feature importance and crossover both are designed to ensure the quality of particles in the subswarms. We apply VS-CCPSO to 12 typical datasets and compare it with six state-of-the-art methods. The experimental results show that VS-CCPSO has the capability of obtaining good feature subsets, suggesting its competitiveness for tackling FS problems with high dimensionality.
Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to ...prevent cancer progression. We aimed to determine whether blocking extracellular ATP-P2RY2 axis could be a potential therapeutic approach for PDAC treatment.
Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression.
P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT-mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice.
These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.
•Proposing a binary differential evolution algorithm with self-learning strategy, called MOFS-BDE, to solve multi-objective feature selection problems.•Proposing a new binary mutation operator based ...on probability difference to guide the individuals to locate potentially optimal areas fast.•Proposing a new one-bit purifying search operator (OPS) for improving the self-learning capability of elite individuals.•Proposing an efficient non-dominated sorting operator with crowding distance to reduce the time consumption of the selection operator in differential evolution.
Feature selection is an important data preprocessing method. This paper studies a new multi-objective feature selection approach, called the Binary Differential Evolution with self-learning (MOFS-BDE). Three new operators are proposed and embedded into the MOFS-BDE to improve its performance. The novel binary mutation operator based on probability difference can guide individuals to rapidly locate potentially optimal areas, the developed One-bit Purifying Search operator (OPS) can improve the self-learning capability of the elite individuals located in the optimal areas, and the efficient non-dominated sorting operator with crowding distance can reduce the computational complexity of the selection operator in the differential evolution. Experimental results on a series of public datasets show that the effective combination of the binary mutation and OPS makes our MOFS-BDE achieve a trade-off between local exploitation and global exploration. The proposed method is competitive in comparison with some representative genetic algorithm-, particle swarm-, differential evolution-, and artificial bee colony-based feature selection algorithms.
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The current power conversion efficiencies of laboratory‐sized organic solar cells (OSCs), based on the spin‐coating process with halogenated solvents, have exceeded 19%. Environmentally friendly ...printing is needed to bridge the gap between laboratory and industrialization by being compatible with roll‐to‐roll large‐area production. Here, the molecular design rules are revealed for enhancing the green printing potential of the state‐of‐the‐art photovoltaic martial systems by investigating the detailed structure formation dynamic and the key determining factors. By comparing two model systems based on D18:Y6 and D18:BTP‐eC9, it is found that disordered preaggregation in liquid state can result in over‐sized domains with reduced crystallinity and disordered molecular orientation, which significantly limits device performance. By systematically tuning the length of the inner alkyl side chains with multiple Y‐series materials, the authors demonstrate that molecular side‐chain engineering can effectively supress the detrimental disordered preaggregation in liquid state during environmentally friendly printing process, leading to enhanced crystallization with preferential faceon molecular orientation, more efficient exciton dissociation and charge carrier transport, and finally high upscaling potential. The work provides deeper insights into molecular engineering and structure formation dynamics toward environmentally friendly production of OSCs.
Disordered preaggregation in liquid state during environmentally friendly printing of organic solar cells significantly limits device performance based on nonfullerene acceptors. Molecular side‐chain engineering can effectively tune this disordered preaggregation in liquid state, leading to enhanced crystallization with preferential face on molecular orientation, more efficient exciton dissociation and charge carrier transport, and finally good upscaling potential.
MicroRNAs (miRNAs) are dysregulated in human ovarian carcinoma (OC). But the mechanism underlying miR‐10a‐5p in regulating the progression of OC need deeply explored. In the current study, we ...observed that miR‐10a‐5p was down‐expressed in OC samples and OC cell lines. In addition, miR‐10a‐5p restrained the viability, colony formation, migration ability and invasiveness of OC cells. We further ascertained Homeobox A1 (HOXA1) was a downstream gene of miR‐10a‐5p. Furthermore, HOXA1 was distinctly upregulated in OC samples. Finally, upregulation of HOXA1 abolished the suppressive effects of miR‐10a‐5p on OC cells. These observations suggested that miR‐10a‐5p suppressed the aggressive phenotypes of OC cells via regulating HOXA1.
Abstract
Objectives
To gauge the relative accuracy of the use of passive and active dynamic navigation systems when placing dental implants, and to determine how registration areas affect the ...performance of these systems.
Materials and Methods
Eighty implants were assigned to be placed into 40 total resin mandible models missing either the left or right first molars using either passive or active dynamic navigation system approaches. U‐shaped tube registration devices were fixed in the edentulous site for 20 models each on the left or right side. Planned and actual implant positions were superimposed to assess procedural accuracy, and parameters including 3D entry deviation, angular deviation, and 3D apex deviation were evaluated with Mann–Whitney
U
tests and Wilcoxon signed‐rank tests.
Results
Respective angular, entry, and apex deviation values of 1.563 ± 0.977°, 0.725 ± 0.268 mm, and 0.808 ± 0.284 mm were calculated for all included implants, with corresponding values of 1.388 ± 1.090°, 0.789 ± 0.285 mm, and 0.846 ± 0.301 mm in the active group and 1.739 ± 0.826°, 0.661 ± 0.236 mm, and 0.769 ± 0.264 mm in the passive group. Only angular deviation differed significantly among groups, and the registration area was not associated with any significant differences among groups.
Conclusions
Passive and active dynamic navigation approaches can achieve comparable in vitro accuracy. Registration on one side of the missing single posterior tooth area in the mandible can complete single‐tooth implantation on both sides of the posterior teeth, highlighting the promise of further clinical research focused on this topic.
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