bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of climate-induced increased risk of Centaurea solstitialis L. invasion in China: An integrated study based on biomod2
Authors: Jia Tao , Qi Yuhan , Zhao Haoxiang , Xian Xiaoqing , Li Jianyu , Huang Hongkun , Yu Wentao , Liu Wan-xue
Published: February 2023

Introduction

Invasive alien plants (IAPs) are major hazards to biodiversity, human health, and the agricultural economy. As one of the most aggressive species of IAPs, the distribution area of Centaurea solstitialis L. has increased exponentially in the past two years since its invasion into Xinjiang, China, in July 2014. Predicting the potential geographic distributions (PGDs) of C. solstitialis in China can provide theoretical support for preventing the continued spread of this weed.

Methods

In this study, based on 5,969 valid occurrence records of C. solstitialis and 33 environmental variables, we constructed an ensemble model to predict suitable habitats for C. solstitialis under climate change scenarios.

Results

Our results showed that the mean true skill statistic (TSS) values, area under the receiver operating characteristic (ROC) curve (AUC), and Cohen’s Kappa (KAPPA) for the ensemble model were 0.954, 0.996, and 0.943, respectively. The ensemble model yielded more precise predictions than those of the single model. Temperature seasonality (Bio4), minimum temperature of the coldest month (Bio6), precipitation of the driest month (Bio14), and human influence index (HII) have significantly disrupted the PGDs of C. solstitialis in China. The total (high) suitability habitat area of C. solstitialis in China was 275.91 × 104 (67.78 × 104) km2, accounting for 71.26 (7.06)% of China. The PGDs of C. solstitialis in China under the current climate were mainly in East China (Shandong, Jiangsu, Shanghai, Zhejiang, and Anhui), Central China (Henan, southwestern Shanxi, southern Shaanxi, southern Gansu, Hubei, Hunan, Jiangxi, Chongqing, and Guizhou), and South China (southern Tibet, eastern Sichuan, Yunnan, Guangxi, Guangdong, Fujian, and Taiwan). Under future climate scenarios, the total suitability habitat area for C. solstitialis will expand, whereas the high suitability habitat area will decrease.

Discussion

The main manifestation is that the shift of southeast China into a moderate suitability habitat, and the total suitability habitats will be extended to northwest China. More focus needs to be placed on preventing further spread of C. solstitialis in northwest China.
Whole genome methylation combined with RNA-seq reveals the protective effects of Gualou-Xiebai herb pair in foam cells through DNA methylation mediated PI3K-AKT signaling pathway
Authors: Jia Zijun , Mei Jun , Zhang Yan , Wang Ya , Wang Hongqin , Wang Anlu , Xu Fengqin , Zhou Qingbing
Published: February 2023

DNA methylation, including aberrant hypomethylation and hypermethylation, plays a significant role in atherosclerosis (AS); therefore, targeting the unbalanced methylation in AS is a potential treatment strategy. Gualou-xiebai herb pair (GXHP), a classic herb combination, have been used for the treatment of atherosclerotic-associated diseases in traditional Chinese medicine. However, the effects and underlying mechanism of GXHP on AS remain nebulous. In this study, the CCK-8 method was applied to determine the non-toxic treatment concentrations for GXHP. The formation of foam cells played a critical role in AS, so the foam cells model was established after RAW264.7 cells were treated with ox-LDL. The contents of total cholesterol (TC) and free cholesterol (FC) were determined by Gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was used to check the expressions of inflammatory factors including IL-1β, TNF-α, and VCAM-1. Methyl-capture sequencing (MC-seq) and RNA-seq were applied to observe the changes in genome-wide DNA methylation and gene expression, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze differentially methylated genes (DMGs) and differentially expressed genes (DEGs). The targeted signaling pathway was selected and verified using western blotting (WB). The results showed that the lipids and inflammatory factors in foam cells significantly increased. GXHP significantly reduced the expression of TC, FC, and inflammatory factors. MC-seq and RNA-seq showed that GXHP not only corrected the aberrant DNA hypermethylation, but also DNA hypomethylation, thus restored the aberrant DEGs in foam cells induced by ox-LDL. GXHP treatment may target the PI3K-Akt signaling pathway. GXHP reduced the protein levels of phosphorylated(p)-PI3K and p-AKT in foam cells. Our data suggest that treatment with GXHP showed protective effects against AS through the inhibition of DNA methylation mediated PI3K-AKT signaling pathway, suggesting GXHP as a novel methylation-based agent.
Smoking is an independent but not a causal risk factor for moderate to severe psoriasis: A Mendelian randomization study of 105,912 individuals
Authors: Näslund-Koch Charlotte , Vedel-Krogh Signe , Bojesen Stig Egil , Skov Lone
Published: February 2023

Background

Smoking is strongly associated with higher risk of psoriasis in several observational studies; however, whether this association is causal or can be explained by confounding or reverse causation is not fully understood. Randomized controlled trials are the gold standard when examining causality; however, when this method is not feasible, the Mendelian randomization design is an alternative. Herein genetic variants can be used as robust proxies for modifiable exposures and thereby avoiding confounding and reverse causation.

In this study, we hypothesized that smoking is an independent and causal risk factor for psoriasis and tested this using a Mendelian randomization design.

Methods

We used data from the Copenhagen General Population Study including 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data. In total, 1,240 cases of moderate to severe psoriasis were included to investigate the association between smoking and psoriasis. To assess causality of the association, we used the genetic variant CHRNA3 rs1051730, where the T-allele is strongly associated with high lifelong cumulative smoking, as a proxy for smoking.

Results

In observational analyses, the multivariable adjusted hazard ratio of developing moderate to severe psoriasis was 1.64 (95% confidence interval: 1.35-2.00) in ever smokers with ≤ 20 pack-years and 2.23 (1.82-2.73) in ever smokers with > 20 pack-years compared to never smokers. In genetic analyses, the odds ratio of developing moderate to severe psoriasis was 1.05 (0.95-1.16) per CHRNA3 rs10511730 T-allele in ever smokers.

Conclusion

Smoking was an independent risk factor for moderate to severe psoriasis in observational analyses. However, using a genetic variant as a robust proxy for smoking, we did not find this association to be causal.
High genetic diversity revealed in the native populations of Undaria pinnatifida from China by mitochondrial sequences and nuclear microsatellites
Authors: Li Yuqian , Shan Tifeng , Pang Shaojun
Published: February 2023

According to historical documents, China has its own native Undaria pinnatifida populations in Zhejiang and Fujian provinces, and they are potentially valuable breeding materials for this economically important kelp. However, their distribution range has been declining northward and we cannot find it now in Fujian province and southern Zhejiang province. They are currently confirmed to be distributed only on some small islands distant from the mainland, likely facing the anthropogenic threats such as habitat deterioration and marine heatwave. Thus, they are of conservation concern. Herein, we used the mitochondrial sequences of cox3 and tatC–tLeu regions, and 10 nuclear microsatellites to analyze the genetic diversity and genetic structure of three temporal populations from Gouqi Island and one population from Yushan Island. A total of eight haplotypes of the combined cox3 and tatC–tLeu sequences were identified with five of them being unique in these populations. Based on microsatellites, we estimated a minimum expected heterozygosity of 0.671 and a minimum effective number of alleles of 5.3 within each population, and revealed shallow genetic structure among populations by Bayesian model-based STRUCTURE analysis and low Fst values. We did not detect signs of recent bottleneck in all populations. The high genetic diversity identified in the southern native populations will provide an advantageous basis for them to adapt to the future environmental changes. A thorough field survey about the detailed distribution of the native populations is needed in order to estimate their population size and better protect the natural resources of this important alga.
Recent advances in using diffusion tensor imaging to study white matter alterations in Parkinson’s disease: A mini review
Authors: Shih Yao-Chia , Tseng Wen-Yih Isaac , Montaser-Kouhsari Leila
Published: February 2023

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease with cardinal motor symptoms. In addition to motor symptoms, PD is a heterogeneous disease accompanied by many non-motor symptoms that dominate the clinical manifestations in different stages or subtypes of PD, such as cognitive impairments. The heterogeneity of PD suggests widespread brain structural changes, and axonal involvement appears to be critical to the pathophysiology of PD. As α-synuclein pathology has been suggested to cause axonal changes followed by neuronal degeneration, diffusion tensor imaging (DTI) as an in vivo imaging technique emerges to characterize early detectable white matter changes due to PD. Here, we reviewed the past 5-year literature to show how DTI has helped identify axonal abnormalities at different PD stages or in different PD subtypes and atypical parkinsonism. We also showed the recent clinical utilities of DTI tractography in interventional treatments such as deep brain stimulation (DBS). Mounting evidence supported by multisite DTI data suggests that DTI along with the advanced analytic methods, can delineate dynamic pathophysiological processes from the early to late PD stages and differentiate distinct structural networks affected in PD and other parkinsonism syndromes. It indicates that DTI, along with recent advanced analytic methods, can assist future interventional studies in optimizing treatments for PD patients with different clinical conditions and risk profiles.
A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia
Authors: Dean Brian , Bakker Geor , Ueda Hiroki R. , Tobin Andrew B. , Brown Alastair , Kanaan Richard A. A.
Published: February 2023

Pre-clinical models, postmortem and neuroimaging studies all support a role for muscarinic receptors in the molecular pathology of schizophrenia. From these data it was proposed that activation of the muscarinic M1 and/or M4 receptor would reduce the severity of the symptoms of schizophrenia. This hypothesis is now supported by results from two clinical trials which indicate that activating central muscarinic M1 and M4 receptors can reduce the severity of positive, negative and cognitive symptoms of the disorder. This review will provide an update on a growing body of evidence that argues the muscarinic M1 and M4 receptors have critical roles in CNS functions that are dysregulated by the pathophysiology of schizophrenia. This realization has been made possible, in part, by the growing ability to visualize and quantify muscarinic M1 and M4 receptors in the human CNS using molecular neuroimaging. We will discuss how these advances have provided evidence to support the notion that there is a sub-group of patients within the syndrome of schizophrenia that have a unique molecular pathology driven by a marked loss of muscarinic M1 receptors. This review is timely, as drugs targeting muscarinic receptors approach clinical use for the treatment of schizophrenia and here we outline the background biology that supported development of such drugs to treat the disorder.
Experience-dependent plasticity in the olfactory system of Drosophila melanogaster and other insects
Authors: Fabian Benjamin , Sachse Silke
Published: February 2023

It is long known that the nervous system of vertebrates can be shaped by internal and external factors. On the other hand, the nervous system of insects was long assumed to be stereotypic, although evidence for plasticity effects accumulated for several decades. To cover the topic comprehensively, this review recapitulates the establishment of the term “plasticity” in neuroscience and introduces its original meaning. We describe the basic composition of the insect olfactory system using Drosophila melanogaster as a representative example and outline experience-dependent plasticity effects observed in this part of the brain in a variety of insects, including hymenopterans, lepidopterans, locusts, and flies. In particular, we highlight recent advances in the study of experience-dependent plasticity effects in the olfactory system of D. melanogaster, as it is the most accessible olfactory system of all insect species due to the genetic tools available. The partly contradictory results demonstrate that morphological, physiological and behavioral changes in response to long-term olfactory stimulation are more complex than previously thought. Different molecular mechanisms leading to these changes were unveiled in the past and are likely responsible for this complexity. We discuss common problems in the study of experience-dependent plasticity, ways to overcome them, and future directions in this area of research. In addition, we critically examine the transferability of laboratory data to natural systems to address the topic as holistically as possible. As a mechanism that allows organisms to adapt to new environmental conditions, experience-dependent plasticity contributes to an animal’s resilience and is therefore a crucial topic for future research, especially in an era of rapid environmental changes.
Derivation and validation of a composite scoring system (SAVED2) for prediction of unfavorable modified Rankin scale score following intracerebral hemorrhage
Authors: Coleman Craig I. , Concha Mauricio , Koch Bruce , Lovelace Belinda , Christoph Mary J. , Cohen Alexander T.
Published: February 2023

Objective

To develop a composite score for predicting functional outcome post–intracerebral hemorrhage (ICeH) using proxy measures that can be assessed retrospectively.

Methods

Data from the observational ERICH study were used to derive a composite score (SAVED2) to predict an unfavorable 90-day modified Rankin scale (mRS) score. Independent predictors of unfavorable mRS were identified via multivariable logistic regression and assigned score weights based on effect size. Area under the curve (AUC) was used to measure the score's discriminative ability. External validation was performed in the randomized ATACH-2 trial.

Results

There were 2,449 patients from ERICH with valid mRS data who survived to hospital discharge. Predictors associated with unfavorable 90-day mRS score and their corresponding point values were: age ≥70 years (odds ratio [OR], 3.8; 1-point); prior stroke (OR, 2.8; 1-point); need for ventilation (OR, 2.7; 1-point); extended hospital stay (OR, 2.7; 1-point); and non-home discharge location (OR, 5.3; 2-points). Incidence of unfavorable 90-day mRS increased with higher SAVED2 scores (P < 0.001); AUC in ERICH was 0.82 (95% CI, 0.80–0.84). External validation in ATACH-2 (n = 904) found an AUC of 0.74 (95% CI, 0.70–0.77).

Conclusions

Using data collected at hospital discharge, the SAVED2 score predicted unfavorable mRS in patients with ICeH.
Single-trial P300 classification algorithm based on centralized multi-person data fusion CNN
Authors: Du Pu , Li Penghai , Cheng Longlong , Li Xueqing , Su Jianxian
Published: February 2023

Introduction

Currently, it is still a challenge to detect single-trial P300 from electroencephalography (EEG) signals. In this paper, to address the typical problems faced by existing single-trial P300 classification, such as complex, time-consuming and low accuracy processes, a single-trial P300 classification algorithm based on multiplayer data fusion convolutional neural network (CNN) is proposed to construct a centralized collaborative brain-computer interfaces (cBCI) for fast and highly accurate classification of P300 EEG signals.

Methods

In this paper, two multi-person data fusion methods (parallel data fusion and serial data fusion) are used in the data pre-processing stage to fuse multi-person EEG information stimulated by the same task instructions, and then the fused data is fed as input to the CNN for classification. In building the CNN network for single-trial P300 classification, the Conv layer was first used to extract the features of single-trial P300, and then the Maxpooling layer was used to connect the Flatten layer for secondary feature extraction and dimensionality reduction, thereby simplifying the computation. Finally batch normalisation is used to train small batches of data in order to better generalize the network and speed up single-trial P300 signal classification.

Results

In this paper, the above new algorithms were tested on the Kaggle dataset and the Brain-Computer Interface (BCI) Competition III dataset, and by analyzing the P300 waveform features and EEG topography and the four standard evaluation metrics, namely Accuracy, Precision, Recall and F1-score,it was demonstrated that the single-trial P300 classification algorithm after two multi-person data fusion CNNs significantly outperformed other classification algorithms.

Discussion

The results show that the single-trial P300 classification algorithm after two multi-person data fusion CNNs significantly outperformed the single-person model, and that the single-trial P300 classification algorithm with two multi-person data fusion CNNs involves smaller models, fewer training parameters, higher classification accuracy and improves the overall P300-cBCI classification rate and actual performance more effectively with a small amount of sample information compared to other algorithms.
Single-nucleus transcriptional profiling uncovers the reprogrammed metabolism of astrocytes in Alzheimer’s disease
Authors: Fan Li-Yuan , Yang Jing , Li Ming-Li , Liu Ruo-Yu , Kong Ying , Duan Su-Ying , Guo Guang-Yu , Yang Jing-Hua , Xu Yu-Ming
Published: February 2023

Astrocytes play an important role in the pathogenesis of Alzheimer’s disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of GLUL (GS) and GLUD1 (GDH) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.
Case report: PD-1 inhibitor-based treatment strategies in gastric cancer complicated by bone marrow metastasis and disseminated intravascular coagulation: A report of two cases
Authors: Huang Ren-Ze , Chen Nuo , Hu Yan , Hu Wan-Ming , Wang Feng-Hua , Chen Dong-Liang
Published: February 2023

Introduction

Gastric cancer (GC) complicated by bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) represents poor prognosis and most of these patients would die in a few months. Active treatment strategies such as chemotherapy are effective in restoring coagulation function and prolonging patients’ survival time. Immunotherapy including programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1) inhibitors has emerged as a first-line treatment of gastric cancer. However, the efficacy of PD-1 inhibitor-based treatment strategies in these patients remains unknown.

Case description

Herein, we presented two cases of advanced gastric cancer (AGC) complicated by BMM and DIC, in which two patients received chemotherapy and PD-1 inhibitor as the first-line treatment. Both of them achieved a partial response after treatment, and the coagulation function was restored. The patient who discontinued the PD-1 inhibitor after 6 months experienced DIC relapse, whereas the other patient who maintained the PD-1 inhibitor treatment cycle remained responsive after 10 months.

Conclusions

We speculate that PD-1 inhibitor-based treatment strategies are effective and safe in prolonging survival against gastric cancer with BMM and DIC, and the coagulation function is well controlled by the treatment with a combination of immunotherapy and chemotherapy.
Multivariate analysis of prognostic factors in patients with lung cancer
Authors: Liu Changjiang , Ma Minting , Zhou Xuetao , Zhang Zefeng , Guo Yang
Published: February 2023

Objective

Lung cancer is the leading cause of cancer-related mortality in China. The purpose of this study was to determine the effect of non-therapeutic and therapeutic factors of patients with lung cancer on survival rate.

Methods

In this retrospective study, a total of 458 patients diagnosed as lung cancer at the Department of Thoracic Surgery, the Fourth Affiliated Hospital of Hebei Medical University from September 2008 to October 2013 were enrolled. The COX proportional hazards model was used to analyze the possible factors affecting the survival of patients. Model variables included age, sex, family history, smoking, tumor location, pathological type, stage, chemotherapy, radiotherapy, operation, and targeted therapy.

Results

The median survival time (MST) was 32.0 months (95% CI: 29.0-34.0 months), while the 1-, 3-, and 5-year survival rates were 70.74%, 36.90%, and 30.13%, respectively. The univariate analysis showed that stage, chemotherapy, radiotherapy, and operation significantly affected the median survival time of patients. Multivariate cox regression analysis suggested that sex (female vs male, 2.096, 95% CI: 1.606-2.736), stage (stage I vs IV, 0.111, 95% CI: 0.039-0.314; stage II vs IV, 0.218, 95%CI: 0.089-0.535), chemotherapy (no vs yes, 0.469, 95% CI: 0.297-0.742), and operation (no vs yes, 2.667, 95% CI: 1.174-6.055) were independently associated with the survival of patients with lung cancer.

Conclusion

Our study showed that male, early stage, operation were protective factors for the survival of patients, while female, advanced stage, chemotherapy were risk factors for the survival of patients. Larger studies are required to address the usefulness of these prognostic factors in defining the management of patients with lung cancer.
A potential link between aberrant expression of ECRG4 and atrial fibrillation
Authors: Zhang Zuojing , Wang Wei , Zhang Yuxin , You Xingji , Wu Jingxiang
Published: February 2023

Esophageal cancer-related gene-4 (ECRG4), a 148-amino acid propertied and new tumor suppressor, is initially cloned from the normal esophageal epithelium. ECRG4 was found to be expressed not only in esophageal tissues but also in cardiomyocytes. Previous studies demonstrated that ECRG4 is constitutively expressed in esophageal epithelial cells, and its degree of downregulation is directly proportional to prognosis in patients with esophageal cancer. In the heart, ECRG4 shows greater expression in the atria than in the ventricles, which accounts for its heterogeneity. Downregulation of ECRG4 expression level correlates with esophageal cancer, as well as myocardial injuries and arrhythmias. As a result, this review summarizes the possible susceptibility gene, ECRG4 and its associated molecular mechanisms in cancer patients with atrial fibrillation and myocardial injury. The review begins by describing ECRG4’s biological background, discusses its expression in the cardiovascular system, lists the clinical and animal research related to the downregulation of ECRG4 in atrial fibrillation, and focuses on its potential role in atrial fibrillation. Downregulation of ECRG4 may increase the risk of atrial fibrillation by affecting ion channels, MMPs expression and inflammatory response. We will then discuss how ECRG4 can be used in the treatment of tumors and arrhythmias, and provide a novel possible strategy to reduce the occurrence of perioperative cardiovascular adverse events in patients with tumors such as esophageal cancer and gastric cancer.
Machine learning-based neddylation landscape indicates different prognosis and immune microenvironment in endometrial cancer
Authors: Li Yi , Niu Jiang-Hua , Wang Yan
Published: February 2023

Endometrial cancer (EC) is women’s fourth most common malignant tumor. Neddylation plays a significant role in many diseases; however, the effect of neddylation and neddylation-related genes (NRGs) on EC is rarely reported. In this study, we first used MLN4924 to affect the activation of neddylation in different cell lines (Ishikawa and HEC-1-A) and determined the critical role of neddylation-related pathways for EC progression. Subsequently, we screened 17 prognostic NRGs based on expression files of the TCGA-UCEC cohort. Based on unsupervised consensus clustering analysis, patients with EC were classified into two neddylation patterns (C1 and C2). In terms of prognosis, substantial differences were observed between the two patterns. Compared with C2, C1 exhibited low levels of immune infiltration and promoted tumor progression. More importantly, based on the expression of 17 prognostic NRGs, we transformed nine machine-learning algorithms into 89 combinations. The random forest (RSF) was selected to construct the neddylation-related risk score according to the average C-index of different cohorts. Notably, our score had important clinical implications for EC. Patients with high scores have poor prognoses and a cold tumor state. In conclusion, neddylation-related patterns and scores can distinguish tumor microenvironment (TME) and prognosis and guide personalized treatment in patients with EC.
Iron metabolism in colorectal cancer
Authors: Huang Luji , Li Wangji , Lu Yan , Ju Qinuo , Ouyang Manzhao
Published: February 2023

Iron, as one of the essential trace elements in the human body, is involved in a wide range of critical biochemical reactions and physiological processes, including the maintenance of the normal cell cycle, mitochondrial function, nucleotide metabolism, and immune response. In this context, iron is naturally associated with cancer occurrence. Cellular iron deficiency can induce apoptosis, however, iron can also engage in potentially harmful reactions that produce free radicals because of its capacity to gain and lose electrons. Studies suggest that dietary iron, particularly heme iron, may be one of the leading causes of colorectal cancer (CRC). Moreover, patients with CRC have abnormal iron absorption, storage, utilization, and exportation. Therefore, iron is crucial for the development and progression of CRC. Elaborating on the alterations in iron metabolism during the onset and advancement of CRC would help to further explain the role and mechanism of iron inside the body. Thus, we reviewed the alterations in numerous iron metabolism-related molecules and their roles in CRC, which may provide new clues between iron metabolism and CRC.
Case Report: The effective treatment of patients in advanced no-small cell lung cancer patients with EGFR G719X/S768I/L861Q and acquired MET amplification: A case series and literature review
Authors: Zhao Yun , Su Cuiyun , Shi Lina , Luo Wenqi , Liu Zhen , Liang Chuqiao , Wang Huilin , Ning Ruiling , Yu Qitao , Jiang Wei
Published: February 2023

Preclinical cases suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a potential therapy for non-classical EGFR mutant lung cancers with MET amplification acquired resistance. Herein, we report for the first time the effectiveness of novel combination treatment regimens for patients with EGFR G719X/S768I/L861Q. Until the last follow-up assessment, two patients demonstrated improved survival after they switched to afatinib combined with savolitinib (PFS: 10 months) and furmonertinib combined with crizotinib (PFS: 6 months), respectively, that did not observed increased incidence and severity of adverse events. According to the findings of this study and literature review, various responses were observed from the combined therapy in NSCLC patients who harbored uncommon EGFR mutations and MET amplification. Furthermore, Next generation sequencing (NGS) leads to the discovery of uncommon of EGFR and reveals the co-mutations in NSCLC.
Incorporating the synthetic CT image for improving the performance of deformable image registration between planning CT and cone-beam CT
Authors: Li Na , Zhou Xuanru , Chen Shupeng , Dai Jingjing , Wang Tangsheng , Zhang Chulong , He Wenfeng , Xie Yaoqin , Liang Xiaokun
Published: February 2023

Objective

To develop a contrast learning-based generative (CLG) model for the generation of high-quality synthetic computed tomography (sCT) from low-quality cone-beam CT (CBCT). The CLG model improves the performance of deformable image registration (DIR).

Methods

This study included 100 post-breast-conserving patients with the pCT images, CBCT images, and the target contours, which the physicians delineated. The CT images were generated from CBCT images via the proposed CLG model. We used the Sct images as the fixed images instead of the CBCT images to achieve the multi-modality image registration accurately. The deformation vector field is applied to propagate the target contour from the pCT to CBCT to realize the automatic target segmentation on CBCT images. We calculate the Dice similarity coefficient (DSC), 95 % Hausdorff distance (HD95), and average surface distance (ASD) between the prediction and reference segmentation to evaluate the proposed method.

Results

The DSC, HD95, and ASD of the target contours with the proposed method were 0.87 ± 0.04, 4.55 ± 2.18, and 1.41 ± 0.56, respectively. Compared with the traditional method without the synthetic CT assisted (0.86 ± 0.05, 5.17 ± 2.60, and 1.55 ± 0.72), the proposed method was outperformed, especially in the soft tissue target, such as the tumor bed region.

Conclusion

The CLG model proposed in this study can create the high-quality sCT from low-quality CBCT and improve the performance of DIR between the CBCT and the pCT. The target segmentation accuracy is better than using the traditional DIR.
Retrospective validation of G-ROP, CO-ROP, Alex-ROP, and ROPscore predictive algorithms in two Chinese medical centers
Authors: Lu Yang , Lv Zhe , Cen Jiner , Tao Jiwei , Zhang Yun , Zhang Yifan , Mao Jianbo , Chen Yiqi , Wu Mingyuan , Chen Shujun , Shen Lijun
Published: February 2023

Purpose

To evaluate the sensitivity and specificity of four predictive algorithms (G-ROP, CO-ROP, Alex-ROP, and ROPscore) for retinopathy of prematurity and compare their performances in the Chinese population.

Methods

A retrospective study was conducted at two medical centers in China of infants born at Women's Hospital School of Medicine Zhejiang University and Yiwu Maternal and Child Health Hospital. A total of 1,634 infants who met the criteria and who were GA < 32 weeks or BW < 2,000 g according to Chinese guidelines for ROP screening were included. The ROP group was further grouped into severe ROP and mild ROP. The sensitivity and specificity of G-ROP, two simplified G-ROPs, CO-ROP, Alex-ROP, and ROPscore were analyzed.

Results

Severe ROP and any ROP were identified in 25 and 399 of 1,634 infants, respectively. According to the criteria of different models, 844, 1,122, 1,122, and 587 infants were eligible in the G-ROP, CO-ROP, Alex-ROP, and ROPscore, respectively. G-ROP had 96.0% sensitivity and 35.0% specificity for severe ROP. For two simplified G-ROPs (180 g and 200 g models), similar sensitivity was showed with original G-ROP and they had specificity of 21.8% and 14.0%, respectively. The sensitivity and specificity of Co-ROP were 96% and 64.3% for severe ROP, while Alex-ROP only had sensitivity of 56.0% and specificity of 61.4% for severe ROP. ROPscore had a sensitivity of 91.3% and a specificity of 62.4% for severe ROP. In 546 infants who met all 4 models' inclusion criteria and included 23 infants with severe ROP, the validation outcomes showed the sensitivity of G-ROP, ROPscore, CO-ROP, and Alex-ROP for severe ROP was 95.6%, 91.3%, 100%, and 56.0%, and their specificity was 38.0%, 60.8%, 39.9%, and 52.9%, respectively.

Conclusion

G-ROP, ROPscore, and CO-ROP had high sensitivity for severe ROP in the Chinese population, but both the sensitivity and specificity of Alex-ROP were low. CO-ROP (not high-grade CO-ROP) provided the best performance for severe ROP in a fair comparison. For further application, ROP screening models need to be adjusted by local populations.
Extracellular vesicles mediate biological information delivery: A double-edged sword in cardiac remodeling after myocardial infarction
Authors: Cheng Peipei , Wang Xinting , Liu Qian , Yang Tao , Qu Huiyan , Zhou Hua
Published: February 2023

Acute myocardial infarction (AMI) is a severe ischemic disease with high morbidity and mortality worldwide. Maladaptive cardiac remodeling is a series of abnormalities in cardiac structure and function that occurs following myocardial infarction (MI). The pathophysiology of this process can be separated into two distinct phases: the initial inflammatory response, and the subsequent longer-term scar revision that includes the regression of inflammation, neovascularization, and fibrotic scar formation. Extracellular vesicles are nano-sized lipid bilayer vesicles released into the extracellular environment by eukaryotic cells, containing bioinformatic transmitters which are essential mediators of intercellular communication. EVs of different cellular origins play an essential role in cardiac remodeling after myocardial infarction. In this review, we first introduce the pathophysiology of post-infarction cardiac remodeling, as well as the biogenesis, classification, delivery, and functions of EVs. Then, we explore the dual role of these small molecule transmitters delivered by EVs in post-infarction cardiac remodeling, including the double-edged sword of pro-and anti-inflammation, and pro-and anti-fibrosis, which is significant for post-infarction cardiac repair. Finally, we discuss the pharmacological and engineered targeting of EVs for promoting heart repair after MI, thus revealing the potential value of targeted modulation of EVs and its use as a drug delivery vehicle in the therapeutic process of post-infarction cardiac remodeling.
Does China’s competitive generic substitution policy deliver equivalent clinical outcomes? A pilot study with two generic formulations of olanzepine
Authors: Zhang Chao , Ding Yudan , Wu Zhenzhen , Wang Juan , Wu Xiangping , Xie Weiwei
Published: February 2023

With the National Centralized Drug Procurement policy gradually applied nationally in China, concerns about the effectiveness and safety of bid-winning generic drugs are growing again, but relevant studies are lacking. This real-world, before-and-after study was conducted to explore the clinical effects of switching between two versions of generic olanzapine (one of them was bid-winning product). Pre-and post-switching serum olanzapine concentrations were compared. A total of 30 patients were included and results showed the log-transformed, dose-adjusted concentration of bid-winning generic olanzapine was significantly lower than that of another generic olanzapine, while no significant differences were shown on Clinical Global Impressions Severity of Illness or Improvement ratings before and after switching. This study suggest that a generic version of a psychotropic medication may not be of therapeutic equivalence or bioequivalence with another generic one. Changes in efficacy or tolerability are possible in every switch. Therapeutic drug monitoring could be a valuable tool during switches between generic drugs. Larger prospective clinical studies for other generic psychotropic medications in target populations are warranted.
The potential role of nanomedicine in the treatment of breast cancer to overcome the obstacles of current therapies
Authors: Yang Fan , He Qingjie , Dai Xiangpeng , Zhang Xiaoling , Song Dong
Published: February 2023

Breast cancer (BC) is the most frequently diagnosed malignant tumor among women in the world. BC is the heterogeneous tumor with different subtypes including luminal A-like, luminal B-like (HER2-/HER2+), HER2 enriched, and triple-negative BC. The therapeutic strategies including surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy are well developed and commonly used in the treatment of BC. However, some adverse effects of these conventional treatments limited their wide application in clinical. Therefore, it is necessary to develop more safe and more efficient individualized treatment strategies of the BC. Nanomedicine, as the most promising strategy for controlled and targeted drug delivery, is widely used in multiple aspects of cancer therapy. Importantly, accumulative evidences show that nanomedicine has achieved good outcomes in the treatment of BC and a huge amount of BC patients benefited from the nanomedicine related treatments. In this review, we summarized and discussed the major problems occurred during the administration of conventional treatment strategies for BC and the potential roles of nanomedicine in promoting the treatment efficacy of BC by overcoming obstacles of current treatment of BC.
Inhibition of EPAC1 signaling pathway alters atrial electrophysiology and prevents atrial fibrillation
Authors: Guillot Bastien , Boileve Arthur , Walton Richard , Harfoush Alexandre , Conte Caroline , Sainte-Marie Yannis , Charron Sabine , Bernus Olivier , Recalde Alice , Sallé Laurent , Brette Fabien , Lezoualc’h Frank
Published: February 2023

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with increased mortality and morbidity. The Exchange Protein directly Activated by cAMP (EPAC), has been implicated in pro-arrhythmic signaling pathways in the atria, but the underlying mechanisms remain unknown.

Methods: In this study, we investigated the involvement of EPAC1 and EPAC2 isoforms in the genesis of AF in wild type (WT) mice and knockout (KO) mice for EPAC1 or EPAC2. We also employed EPAC pharmacological modulators to selectively activate EPAC proteins (8-CPT-AM; 10 μM), or inhibit either EPAC1 (AM-001; 20 μM) or EPAC2 (ESI-05; 25 μM). Transesophageal stimulation was used to characterize the induction of AF in vivo in mice. Optical mapping experiments were performed on isolated mouse atria and cellular electrophysiology was examined by whole-cell patch-clamp technique.

Results: In wild type mice, we found 8-CPT-AM slightly increased AF susceptibility and that this was blocked by the EPAC1 inhibitor AM-001 but not the EPAC2 inhibitor ESI-05. Consistent with this, in EPAC1 KO mice, occurrence of AF was observed in 3/12 (vs. 4/10 WT littermates) and 4/10 in EPAC2 KO (vs. 5/10 WT littermates). In wild type animals, optical mapping experiments revealed that 8-CPT-AM perfusion increased action potential duration even in the presence of AM-001 or ESI-05. Interestingly, 8-CPT-AM perfusion decreased conduction velocity, an effect blunted by AM-001 but not ESI-05. Patch-clamp experiments demonstrated action potential prolongation after 8-CPT-AM perfusion in both wild type and EPAC1 KO mice and this effect was partially prevented by AM-001 in WT.

Conclusion: Together, these results indicate that EPAC1 and EPAC2 signaling pathways differentially alter atrial electrophysiology but only the EPAC1 isoform is involved in the genesis of AF. Selective blockade of EPAC1 with AM-001 prevents AF in mice.
Phylogenomics and phylogeography of Menispermum (Menispermaceae)
Authors: Song Shiqiang , Cameron Kenneth M. , Wang Yuguo , Wang Shenyi , Jin Xinjie , Hina Faiza , Yang Zhaoping , Li Pan
Published: February 2023

Introduction

Phylogenomics have been widely used to resolve ambiguous and controversial evolutionary relationships among plant species and genera, and the identification of unique indels in plastomes may even help to understand the evolution of some plant families.MenispermumL. (Menispermaceae) consists of three species,M. dauricumDC.,M. canadenseL., andM. mexicanumRose, which are disjuncly distributed among East Asia, Eastern North America and Mexico. Taxonomists continue to debate whetherM. mexicanumis a distinct species, a variety ofM. dauricum, or simply a synonym ofM. canadense. To date, no molecular systematics studies have included this doubtful species in phylogenetic analyses.

Methods

In this study, we examined phylogenomics and phylogeography ofMenispermumacross its entire range using 29 whole plastomes of Menispermaceae and 18 ITS1&ITS2 sequences of Menispermeae. We reconstructed interspecific relationships ofMenispermumand explored plastome evolution in Menispermaceae, revealing several genomic hotspot regions for the family.

Results and discussion

Phylogenetic and network analyses based on whole plastome and ITS1&ITS2 sequences show thatMenispermumclusters into two clades with high support values, Clade A (M. dauricum) and Clade B (M. canadense+M. mexicanum). However,M. mexicanumis nested withinM. canadenseand, as a result, we support thatM. mexicanumis a synonym ofM. canadense. We also identified important molecular variations in the plastomes of Menispermaceae. Several indels and consequently premature terminations of genes occur in Menispermaceae. A total of 54 regions were identified as the most highly variable plastome regions, with nucleotide diversity (Pi) values > 0.05, including two coding genes (matK,ycf1), four introns (trnK intron,rpl16intron,rps16 intron,ndhA intron), and 48 intergenic spacer (IGS) regions. Of these, four informative hotspot regions (trnH-psbA,ndhF-rpl32,trnK-rps16, andtrnP-psaJ) should be especially useful for future studies of phylogeny, phylogeography and conservation genetics of Menispermaceae.
Children’s drawings as a projective tool to explore and prevent experiences of mistreatment and/or sexual abuse
Authors: Ballús Elisabeth , Comelles Ma Carmen , Pasto Ma Teresa , Benedico Paula
Published: February 2023

Reality shows us that situations of mistreatment and sexual abuse in childhood are still seldom visible, despite their high prevalence around the world. It is essential to detect and address them, especially among children in situations of dire risk or neglect. The purpose of this study is to determine if graphic emotional indicators are expressed in the drawings of the projective Draw-a-Person (D.A.P) test, made by children in situations of dire risk or neglect. The sample is made up of 34 children, between the ages of 5 and 11 (17 girls and 17 boys), attended by Specialised Child and Adolescent Care Services of the Barcelona Town Hall (Spain). The drawings were coded quantitatively. The results indicated that most of the drawings show a frequency of graphic emotional indicators, as well as graphic indicators common to experiences of mistreatment and/or abuse, which confirm the existence of emotional problems. However, no significant differences based on gender and age were found, except for one indicator of sexual abuse (body omitted/distorted), which is significantly more common in the boys. Results also revealed that the drawings of human figure enable the children to express their experiences of traumatic situations which are difficult to verbalize. These findings have important implications for professionals, as the use of this projective technique can help to early identification and design treatment strategies in situations of mistreatment and/or abuse in children and their families.
The relationship between parenting behavior and the personality of kindergarten children
Authors: Däschle Johanna , Hofmann Carmen , Wernicke Jennifer , Ziegenhain Ute , Montag Christian , Kiefer Markus
Published: February 2023

According to Cloninger’s biosocial model of personality touching upon temperament and character, personality development is a lifelong adaptive process that begins in early childhood. Similarly, theories of parenting behavior and attachment predict that associations between personality and parenting behavior should be found in young children. The present study therefore had the goal to investigate, whether associations between parenting behavior and personality in terms of Cloninger’s temperament and character dimensions previously found in adolescence and adults can already be observed in kindergarten children. This study assessed personality in a sample of 324 kindergarten children (169 girls/155 boys) aged 3–6 years (Mage = 4.59, SD = 0.90). Parents rated their children’s temperament and character using the JTCI 3–6 R questionnaire, which has been specifically developed to measure personality dimensions in three to six-year-olds according to Cloninger’s model. Character traits (especially Self-Transcendence), which reach mature levels in adults, may not be reliably assessed in three-year-old children. Parenting behavior was documented using the DEAPQ-EL-GS self-report questionnaire measuring the parenting behavior dimensions Responsiveness and Demandingness. Correlation analyses revealed that responsive parenting behavior was positively related to the personality dimensions Reward Dependence, Self-Directedness, and Self-Transcendence. Demanding parenting behavior was positively related to the personality dimension Novelty Seeking, but negatively related to the personality dimensions Persistence, Self-Directedness and Cooperativeness. Although the cross-sectional design of our study prevents unequivocal conclusions about the causal direction of these associations, our results highlight possible differential consequences of responsive vs. demanding parenting behavior for personality development in children in line with theories of parenting behavior and attachment. Our results thus advance earlier work in adolescents and adults, by showing that parenting behavior influences the development of the child’s personality according to Cloninger’s biosocial model already in three to six-year-olds.