China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, ...treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non‐Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence‐based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts’ consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow‐up visits for gastric cancer.
α‐Allenol is a versatile synthon in organic synthesis. The catalytic asymmetric synthesis of α‐allenols from readily available starting materials remains a prominent challenge, especially when ...simultaneous control over axial and central chirality is required. Herein, we describe the Cr‐catalyzed enantioconvergent allenylation of aldehydes with racemic propargyl halides to rapidly access a wide range of chiral α‐allenols with adjacent axial and central chiralities. This method features excellent regio‐, diastereo‐ and enantioselectivity control with broad substrate scope, and provides facile access to all four stereoisomers when allied with a Mitsunobu reaction. Preliminary mechanistic studies support radical‐based reaction pathways. The synthetic utility is demonstrated by the application in late‐stage functionalization and the formal total synthesis of (+)‐varitriol.
A Cr‐catalyzed enantioconvergent allenylation reaction of aldehydes with racemic propargyl halides has been developed. This robust method employs simple and readily accessible materials, exhibits exceptional functional group tolerance and broad substrate scope, and provides facile access to a wide range of valuable optically enriched α‐allenols with two or three continuous chiral centers, including both central and axial chirality.
Background
High‐ and low‐risk endometrial cancer (EC) differ in whether lymphadenectomy is performed. Assessment of high‐risk EC is essential for planning surgery appropriately.
Purpose
To develop a ...radiomics nomogram for high‐risk EC prediction preoperatively.
Study Type
Retrospective.
Population
In all, 717 histopathologically confirmed EC patients (mean age, 56 years ± 9) divided into a primary group (394 patients from Center A), validation groups 1 and 2 (146 patients from Center B and 177 patients from Centers C–E).
Field Strength/Sequence
1.5/3T scanners; T2‐weighted imaging, diffusion‐weighted imaging, apparent diffusion coefficient, and contrast enhancement sequences.
Assessment
A radiomics nomogram was generated by combining the selected radiomics features and clinical parameters (metabolic syndrome, cancer antigen 125, age, tumor grade following curettage, and tumor size). The area under the curve (AUC) of the receiver operator characteristic was used to evaluate the predictive performance of the radiomics nomogram for high‐risk EC. The surgical procedure suggested by the nomogram was compared with the actual procedure performed for the patients. Net benefit of the radiomics nomogram was evaluated by a clinical decision curve (CDC), net reclassification index (NRI), and integrated discrimination improvement (IDI).
Statistical Tests
Binary least absolute shrinkage and selection operator (LASSO) logistic regression, linear regression, and multivariate binary logistic regression were used to select radiomics features and clinical parameters.
Results
The AUC for prediction of high‐risk EC for the radiomics nomogram in the primary group, validation groups 1 and 2 were 0.896 (95% confidence interval CI: 0.866–0.926), 0.877 (95% CI: 0.825–0.930), and 0.919 (95% CI: 0.879–0.960), respectively. The nomogram achieved good net benefit by CDC analysis for high‐risk EC. NRIs were 1.17, 1.28, and 1.51, and IDIs were 0.41, 0.60, and 0.61 in the primary group, validation groups 1 and 2, respectively.
Data Conclusion
The radiomics nomogram exhibited good performance in the individual prediction of high‐risk EC, and might be used for surgical management of EC.
Level of Evidence
4
Technical Efficacy Stage
2 J. MAGN. RESON. IMAGING 2020;52:1872–1882.
Since the introduction of antibiotics into clinical practices in the 1940s, antibiotics have become an integral part of animal production to meet the increasing human demand for animal-derived foods. ...As a result, industrial-scale animal production has emerged as a hotspot for the evolution and dissemination of antibiotic resistance genes (ARGs), thereby potentially contributing to a looming public health crisis. The knowledge of ARGs in livestock systems has been greatly expanded with the recent development of rapid molecular tools. However, comprehensive reviews on ARGs in the animal industry and possible mitigation solutions are still lacking from a One Health perspective. Here we provide this review focusing on human health risks associated with the antimicrobial (antibiotic and metal) usages, ARGs in livestock animals and aquaculture systems in a One Health perspective to untangle the complexities of ARGs across animals, environments and humans. Specifically, this review covers (1) antimicrobials usages in the animal industry, (2) ARGs in animals affected by selective agents, (3) animal-to-human direct/indirect ARG transmission pathways, and (4) mitigation approaches. We highlighted the burden of using antimicrobials in animals for public and environmental health, and also the urgent needs for mitigating the spread of antibiotic resistance from the livestock and aquaculture industries.
Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in ...witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine‐mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure‐induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention.
The treatment of complex diseases by taking multiple drugs becomes increasingly popular. However, drug-drug interactions (DDIs) may give rise to the risk of unanticipated adverse effects and even ...unknown toxicity. DDI detection in the wet lab is expensive and time-consuming. Thus, it is highly desired to develop the computational methods for predicting DDIs. Generally, most of the existing computational methods predict DDIs by extracting the chemical and biological features of drugs from diverse drug-related properties, however some drug properties are costly to obtain and not available in many cases. In this work, we presented a novel method (namely DPDDI) to predict DDIs by extracting the network structure features of drugs from DDI network with graph convolution network (GCN), and the deep neural network (DNN) model as a predictor. GCN learns the low-dimensional feature representations of drugs by capturing the topological relationship of drugs in DDI network. DNN predictor concatenates the latent feature vectors of any two drugs as the feature vector of the corresponding drug pairs to train a DNN for predicting the potential drug-drug interactions. Experiment results show that, the newly proposed DPDDI method outperforms four other state-of-the-art methods; the GCN-derived latent features include more DDI information than other features derived from chemical, biological or anatomical properties of drugs; and the concatenation feature aggregation operator is better than two other feature aggregation operators (i.e., inner product and summation). The results in case studies confirm that DPDDI achieves reasonable performance in predicting new DDIs. We proposed an effective and robust method DPDDI to predict the potential DDIs by utilizing the DDI network information without considering the drug properties (i.e., drug chemical and biological properties). The method should also be useful in other DDI-related scenarios, such as the detection of unexpected side effects, and the guidance of drug combination.
Under investigation in this paper is a coherently coupled nonlinear Schrödinger system which describes the propagation of polarized optical waves in an isotropic medium. By virtue of the Darboux ...transformation, some new solutions have been generated on the vanishing and non-vanishing backgrounds, including multi-solitons, bound solitons, one-breathers, bound breathers, two-breathers, first-order and higher-order rogue waves. Dynamic behaviors of those solitons, breathers and rogue waves have been discussed through graphic simulation.
Ultraluminous X-Ray Sources Kaaret, Philip; Feng, Hua; Roberts, Timothy P
Annual review of astronomy and astrophysics,
08/2017, Volume:
55, Issue:
1
Journal Article
Peer reviewed
Open access
We review observations of ultraluminous X-ray sources (ULXs). X-ray spectroscopic and timing studies of ULXs suggest a new accretion state distinct from those seen in Galactic stellar-mass black hole ...binaries. The detection of coherent pulsations indicates the presence of neutron-star accretors in three ULXs and therefore apparently super-Eddington luminosities. Optical and X-ray line profiles of ULXs and the properties of associated radio and optical nebulae suggest that ULXs produce powerful outflows, also indicative of super-Eddington accretion. We discuss models of super-Eddington accretion and their relationship to the observed behaviors of ULXs. We review the evidence for intermediate-mass black holes (IMBHs) in ULXs. We consider the implications of ULXs for super-Eddington accretion in active galactic nuclei, heating of the early Universe, and the origin of the black hole binary recently detected via gravitational waves.
Abstract
A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 ...antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months,
p
= 0.0011; 53.3% vs 13.3%,
p
= 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (
p
= 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (
p
< 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (
p
= 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.
Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients ...with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice. We identify irisin as a serum factor that mediates these metabolic effects during progressive kidney injury by inhibiting TGF-β type 1 receptor. Irisin depletion from serum blunts the induction of oxygen consumption rate observed in tubule cells treated with mPGC-1α serum. In mice, recombinant irisin administration attenuates kidney damage and fibrosis and improves kidney functions. We suggest that myokine-mediated muscle-kidney crosstalk can suppress metabolic reprograming and fibrogenesis during kidney disease.
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