bluuebunny/crossref_metadata_2025 huggingface dataset:
A prognostic pyroptosis-related LncRNA classifier associated with the immune landscape and therapy efficacy in glioma
Authors: Zhong Jiasheng , Liu Jie , Huang Zhilin , Zheng Yaofeng , Chen Jiawen , Ji Jingsen , Chen Taoliang , Ke Yiquan
Published: October 2022

Background: Glioma has the highest fatality rate among intracranial tumours. Besides, the heterogeneity of gliomas leads to different therapeutic effects even with the same treatment. Developing a new signature for glioma to achieve the concept of “personalised medicine” remains a significant challenge.

Method: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were searched to acquire information on glioma patients. Initially, correlation and univariate Cox regression analyses were performed to screen for prognostic pyroptosis-related long noncoding RNAs (PRLs). Secondly, 11 PRLs were selected to construct the classifier using certain algorithms. The efficacy of the classifier was then detected by the “timeROC” package for both the training and validation datasets. CIBERSORT and ESTIMATE packages were applied for comparing the differences (variations) in the immune landscape between the high- and low-risk groups. Finally, the therapeutic efficacy of the chemotherapy, radiotherapy, and immunotherapy were assessed using the “oncoPredict” package, survival analysis, and the tumour immune dysfunction and exclusion (TIDE) score, respectively.

Results: A classifier comprising 11 PRLs was constructed. The PRL classifier exhibits a more robust prediction capacity for the survival outcomes in patients with gliomas than the clinical characteristics irrespective of the dataset (training or validation dataset). Moreover, it was found that the tumour landscape between the low- and high-risk groups was significantly different. A high-risk score was linked to a more immunosuppressive tumour microenvironment. According to the outcome prediction and analysis of the chemotherapy, patients with different scores showed different responses to various chemotherapeutic drugs and immunotherapy. Meanwhile, the patient with glioma of WHO grade Ⅳ or aged >50 years in the high risk group had better survival following radiotherapy.

Conclusion: We constructed a PRL classifier to roughly predict the outcome of patients with gliomas. Furthermore, the PRL classifier was linked to the immune landscape of glioma and may guide clinical treatments.
QTL mapping and genomic prediction of resistance to wheat head blight caused by Fusarium verticillioides
Authors: Song Junqiao , Pang Yuhui , Wang Chunping , Zhang Xuecai , Zeng Zhankui , Zhao Dehui , Zhang Leiyi , Zhang Yong
Published: October 2022

Fusarium head blight (FHB), is one of the destructive fugue diseases of wheat worldwide caused by the Fusarium verticillioides (F.v). In this study, a population consisting of 262 recombinant inbred lines (RILs) derived from Zhongmai 578 and Jimai 22 was used to map Quantitative Trait Locus (QTL) for FHB resistance, with the genotype data using the wheat 50 K single nucleotide polymorphism (SNP) array. The percentage of symptomatic spikelet (PSS) and the weighted average of PSS (PSSW) were collected for each RIL to represent their resistance to wheat head blight caused by F.v. In total, 22 QTL associated with FHB resistance were identified on chromosomes 1D, 2B, 3B, 4A, 5D, 7A, 7B, and 7D, respectively, from which 10 and 12 QTL were detected from PSS and PSSW respectively, explaining 3.82%–10.57% of the phenotypic variances using the inclusive composite interval mapping method. One novel QTL, Qfhb. haust-4A.1, was identified, explaining 10.56% of the phenotypic variation. One stable QTL, Qfhb. haust-1D.1 was detected on chromosome 1D across multiple environments explaining 4.39%–5.70% of the phenotypic variation. Forty-seven candidate genes related to disease resistance were found in the interval of Qfhb. haust-1D.1 and Qfhb. haust-4A.1. Genomic prediction accuracies were estimated from the five-fold cross-validation scheme ranging from 0.34 to 0.40 for PSS, and from 0.34 to 0.39 for PSSW in in-vivo inoculation treatment. This study provided new insight into the genetic analysis of resistance to wheat head blight caused by F.v, and genomic selection (GS) as a potential approach for improving the resistance of wheat head blight.
Identification of biomarkers for hepatocellular carcinoma based on single cell sequencing and machine learning algorithms
Authors: Li Weimin , Liu Jixing , Zhu Wenjuan , Jin Xiaoxin , Yang Zhi , Gao Wenzhe , Sun Jichun , Zhu Hongwei
Published: October 2022

Hepatocellular carcinoma (HCC) remains one of the most lethal cancers around the world. Precision oncology will be crucial for further improving the prognosis of HCC patients. Compared with traditional bulk RNA-seq, single-cell RNA sequencing (scRNA-seq) enables the transcriptomes of a great deal of individual cells assayed in an unbiased manner, showing the potential to deeply reveal tumor heterogeneity. In this study, based on the scRNA-seq results of primary neoplastic cells and paired normal liver cells from eight HCC patients, a new strategy of machine learning algorithms was applied to screen core biomarkers that distinguished HCC tumor tissues from the adjacent normal liver. Expression profiles of HCC cells and normal liver cells were first analyzed by maximum relevance minimum redundancy (mRMR) to get a top 50 signature gene feature. For further analysis, the incremental feature selection (IFS) method and leave-one-out cross validation (LOOCV) were conducted to build an optimal classification model and to extract 21 potentially essential biomarkers for HCC cells. Our results provided new insights into HCC pathogenesis that might be valuable for HCC diagnosis and therapy.
Construction of prognostic signature of breast cancer based on N7-Methylguanosine-Related LncRNAs and prediction of immune response
Authors: Cao Jin , Liang Yichen , Gu J. Juan , Huang Yuxiang , Wang Buhai
Published: October 2022

Background: Long non-coding RNA (LncRNA) is a prognostic factor for malignancies, and N7-Methylguanosine (m7G) is crucial in the occurrence and progression of tumors. However, it has not been documented how well m7G-related LncRNAs predict the development of breast cancer (BC). This study aims to develop a predictive signature based on long non-coding RNAs (LncRNAs) associated with m7G to predict the prognosis of breast cancer patients.

Methods: The Cancer Genome Atlas (TCGA) database provided us with the RNA-seq data and matching clinical information of individuals with breast cancer. To identify the signature of N7-Methylguanosine-Related LncRNAs and create a prognostic model, we employed co-expression network analysis, least absolute shrinkage selection operator (LASSO) regression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. The signature was assessed using the Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve. A nomogram and principal component analysis (PCA) were employed to confirm the predictive signature’s usefulness. Then, we examined the drug sensitivity between the two risk groups and utilized single-sample gene set enrichment analysis (ssGSEA) to investigate the association between predictive factors and the tumor immune microenvironment in high-risk and low-risk groups.

Results: Nine m7G-related LncRNAs (LINC01871, AP003469.4, Z68871.1, AC245297.3, EGOT, TFAP2A-AS1, AL136531.1, SEMA3B-AS1, AL606834.2) that are independently associated with the overall survival time (OS) of BC patients make up the signature we developed. For predicting 1-, 3-, and 5-year survival rates, the areas under the ROC curve (AUC) were 0.715, 0.724, and 0.726, respectively. The Kaplan-Meier analysis revealed that the prognosis of BC patients in the high-risk group was worse than that of those in the low-risk group. When compared to clinicopathological variables, multiple regression analysis demonstrated that risk score was a significant independent predictive factor for BC patients. The results of the ssGSEA study revealed a substantial correlation between the predictive traits and the BC patients’ immunological status, low-risk BC patients had more active immune systems, and they responded better to PD1/L1 immunotherapy.

Conclusion: The prognostic signature, which is based on m7G-related LncRNAs, can be utilized to inform patients’ customized treatment plans by independently predicting their prognosis and how well they would respond to immunotherapy.
Modeling and insights into the structural characteristics of drug-induced autoimmune diseases
Authors: Guo Huizhu , Zhang Peitao , Zhang Ruiqiu , Hua Yuqing , Zhang Pei , Cui Xueyan , Huang Xin , Li Xiao
Published: October 2022

The incidence and complexity of drug-induced autoimmune diseases (DIAD) have been on the rise in recent years, which may lead to serious or fatal consequences. Besides, many environmental and industrial chemicals can also cause DIAD. However, there are few effective approaches to estimate the DIAD potential of drugs and other chemicals currently, and the structural characteristics and mechanism of action of DIAD compounds have not been clarified. In this study, we developed the in silico models for chemical DIAD prediction and investigated the structural characteristics of DIAD chemicals based on the reliable drug data on human autoimmune diseases. We collected 148 medications which were reported can cause DIAD clinically and 450 medications that clearly do not cause DIAD. Several different machine learning algorithms and molecular fingerprints were combined to develop the in silico models. The best performed model provided the good overall accuracy on validation set with 76.26%. The model was made freely available on the website http://diad.sapredictor.cn/. To further investigate the differences in structural characteristics between DIAD chemicals and non-DIAD chemicals, several key physicochemical properties were analyzed. The results showed that AlogP, molecular polar surface area (MPSA), and the number of hydrogen bond donors (nHDon) were significantly different between the DIAD and non-DIAD structures. They may be related to the DIAD toxicity of chemicals. In addition, 14 structural alerts (SA) for DIAD toxicity were detected from predefined substructures. The SAs may be helpful to explain the mechanism of action of drug induced autoimmune disease, and can used to identify the chemicals with potential DIAD toxicity. The structural alerts have been integrated in a structural alert-based web server SApredictor (http://www.sapredictor.cn). We hope the results could provide useful information for the recognition of DIAD chemicals and the insights of structural characteristics for chemical DIAD toxicity.
Short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer
Authors: Song Rui , Liu Li , Pan Qingbo , Liu Jin , Tan Jiahe , Deng Juan , Deng Qin , Lin Zijin , Chen Min , Peng Mingli , Ren Hong , Ming Jia
Published: October 2022

Background

The aim of this study was to explore the short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer (ER).

Methods

Eighty-eight patients with ER cancer and 82 healthy controls who had completed a full course of inactivated or peptide-based SARS-CoV-2 vaccines were recruited. Adverse events (AEs) were recorded. Responses to receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD+ memory B cells (MBCs) were evaluated.

Results

Approximately 26.14% (23/88) of patients with ER cancer reported AEs within 7 days, which was comparable to that reported by healthy controls (24.39%, 20/82). Both the overall seroprevalence of anti-RBD-IgG and NAbs was obviously lower in the cancer group (70.45% vs. 86.59%, P < 0.05; 69.32% vs. 82.93%, P < 0.05, respectively). Anti-RBD-IgG and NAbs titers exhibited similar results, and dropped gradually over time. Patients with ongoing treatment had an attenuated immune response, especially in patients receiving active chemotherapy. The frequency of overall RBD+ MBCs was similar between the two groups, but the percentage of active MBCs was remarkably reduced in patients with ER cancer. Unlike antibody titers, MBCs responses were relatively constant over time.

Conclusion

Inactivated and peptide-based COVID-19 vaccines were well tolerated, but with lower immunogenicity for ER cancer patients. More intensive antibody monitoring and timely booster immunization is recommended for patients with ER cancer presenting disordered subpopulations of RBD+ MBCs.
The carotid body: A novel key player in neuroimmune interactions
Authors: Katayama Pedro L. , Leirão Isabela P. , Kanashiro Alexandre , Menani José V. , Zoccal Daniel B. , Colombari Débora S. A. , Colombari Eduardo
Published: October 2022

The idea that the nervous system communicates with the immune system to regulate physiological and pathological processes is not new. However, there is still much to learn about how these interactions occur under different conditions. The carotid body (CB) is a sensory organ located in the neck, classically known as the primary sensor of the oxygen (O2) levels in the organism of mammals. When the partial pressure of O2 in the arterial blood falls, the CB alerts the brain which coordinates cardiorespiratory responses to ensure adequate O2 supply to all tissues and organs in the body. A growing body of evidence, however, has demonstrated that the CB is much more than an O2 sensor. Actually, the CB is a multimodal sensor with the extraordinary ability to detect a wide diversity of circulating molecules in the arterial blood, including inflammatory mediators. In this review, we introduce the literature supporting the role of the CB as a critical component of neuroimmune interactions. Based on ours and other studies, we propose a novel neuroimmune pathway in which the CB acts as a sensor of circulating inflammatory mediators and, in conditions of systemic inflammation, recruits a sympathetic-mediated counteracting mechanism that appears to be a protective response.
CEBPB is associated with active tumor immune environment and favorable prognosis of metastatic skin cutaneous melanoma
Authors: Yang Jingrun , Xu Yang , Xie Kuixia , Gao Ling , Zhong Wenying , Liu Xinhua
Published: October 2022

Metastatic skin cutaneous melanoma (SKCM) is a common malignancy that accounts for low morbidity but high mortality of skin cancer. SKCM is characterized by high lymphocytic infiltration, whereas the states of infiltrated cells are variable in patients leading to a heterogeneous prognosis and hindering appropriate clinical decisions. It is therefore urgent to identify markers associated with lymphocytic infiltration, cellular conditions, and the prognosis of SKCM. In this study, we report that CEBPB, a transcriptional factor, is mainly expressed in macrophages in metastatic SKCM and associated with an active tumor immune environment and a favorable prognosis through integrated analysis of single-cell and bulk RNA-seq datasets. High CEBPB expression is significantly associated with active inflammation and immune response pathways in both macrophages and bulk SKCM tumor tissues. A signature based on CEBPB-associated genes that are specifically expressed in macrophages could robustly and prognostically separate different metastatic SKCM patients. In addition, the associations between the metastatic SKCM tumor signature and microenvironment with respect to T-cell recruitment and state, inflammation response, angiogenesis, and so on were also determined. In conclusion, we present here the first report on CEBPB in tumor immune environment and prognosis regulation in metastatic SKCM and construct a reliable signature, which should provide a useful biomarker for stratification of the patient’s prognosis and therapeutic selection.
Cancer immunotherapy strategies that target the cGAS-STING pathway
Authors: Tian Zhuoying , Zeng Yue , Peng Yurong , Liu Junqi , Wu Fang
Published: October 2022

Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.
Nondestructive testing and evaluation techniques of defects in fiber-reinforced polymer composites: A review
Authors: Chen Jian , Yu Zhenyang , Jin Haoran
Published: October 2022

Fiber-reinforced polymer composites have excellent mechanical properties and outstanding development potential and are cost-effective. They have increasingly been used in numerous advanced and engineering applications as materials for wind turbine blades, helicopter rotors, high-pressure pipelines, and medical equipment. Understanding and assessing structural failure promptly in the whole lifecycle of a composite is essential to mitigating safety concerns and reducing maintenance costs. Various nondestructive testing and evaluation (NDT&E) technologies based on different evaluation principles have been established to inspect defects under different conditions. This paper reviews the established types of NDT&E techniques: acoustic emission, ultrasonic testing, eddy current testing, infrared thermography, terahertz testing, digital image correlation, shearography, and X-ray computed tomography, which is divided into three categories based on the operation frequency and data processing means of the output signal that is directly under analysis. We listed four types of defects/damage that are currently of great interest, namely, voids and porosity, fiber waviness and wrinkling, delamination and debonding, as well as impact damage. To identify a suitable method for different defects/damage, we performed characterization and evaluation by using these NDT&E techniques for typical defects/damage. Then, the cost, inspection speed, benefits and limitations, etc. were compared and discussed. Finally, a brief overview of the development of the technologies and their applications in the field of composite fabrication was discussed.
Unsupervised clustering algorithms improve the reproducibility of dynamic contrast-enhanced magnetic resonance imaging pulmonary perfusion quantification in muco-obstructive lung diseases
Authors: Konietzke Marilisa , Triphan Simon M. F. , Eichinger Monika , Bossert Sebastian , Heller Hartmut , Wege Sabine , Eberhardt Ralf , Puderbach Michael U. , Kauczor Hans-Ulrich , Heußel Gudula , Heußel Claus P. , Risse Frank , Wielpütz Mark O.
Published: October 2022

Background

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the assessment of pulmonary perfusion, which may play a key role in the development of muco-obstructive lung disease. One problem with quantifying pulmonary perfusion is the high variability of metrics. Quantifying the extent of abnormalities using unsupervised clustering algorithms in residue function maps leads to intrinsic normalization and could reduce variability.

Purpose

We investigated the reproducibility of perfusion defects in percent (QDP) in clinically stable patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

Methods

15 CF (29.3 ± 9.3y, FEV1%predicted = 66.6 ± 15.8%) and 20 COPD (66.5 ± 8.9y, FEV1%predicted = 42.0 ± 13.3%) patients underwent DCE-MRI twice 1 month apart. QDP, pulmonary blood flow (PBF), and pulmonary blood volume (PBV) were computed from residue function maps using an in-house quantification pipeline. A previously validated MRI perfusion score was visually assessed by an expert reader.

Results

Overall, mean QDP, PBF, and PBV did not change within 1 month, except for QDP in COPD (p < 0.05). We observed smaller limits of agreement (± 1.96 SD) related to the median for QDP (CF: ± 38%, COPD: ± 37%) compared to PBF (CF: ± 89%, COPD: ± 55%) and PBV (CF: ± 55%, COPD: ± 51%). QDP correlated moderately with the MRI perfusion score in CF (r = 0.46, p < 0.05) and COPD (r = 0.66, p < 0.001). PBF and PBV correlated poorly with the MRI perfusion score in CF (r =−0.29, p = 0.132 and r =−0.35, p = 0.067, respectively) and moderately in COPD (r =−0.57 and r =−0.57, p < 0.001, respectively).

Conclusion

In patients with muco-obstructive lung diseases, QDP was more robust and showed a higher correlation with the MRI perfusion score compared to the traditionally used perfusion metrics PBF and PBV.
Difficult-to-treat rheumatoid arthritis: Current concept and unsolved problems
Authors: Watanabe Ryu , Okano Tadashi , Gon Takaho , Yoshida Naofumi , Fukumoto Kazuo , Yamada Shinsuke , Hashimoto Motomu
Published: October 2022

Over the past several decades, the treatment of rheumatoid arthritis (RA) has advanced significantly, and clinical, structural, and functional remission are achievable therapeutic goals. However, a substantial number of patients show resistance to multiple drugs. In particular, patients whose disease activity cannot be controlled despite the use of two or more biological disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs (tsDMARDs) with different mechanisms of action (MOA) have recently been referred to as having difficult-to-treat RA (D2T RA). D2T RA is a heterogeneous and multifactorial disease state, and the major problems are uncontrolled disease activity and decreased quality of life, as well as the economic burden due to frequent healthcare utilization and multiple admissions. Since the concept of D2T RA is relatively new and publication regarding D2T RA is limited, the mechanism underlying DMARD inefficacy and which factors form a “difficult-to-treat” state in such patients are not yet fully understood. It is also possible that factors contributing to D2T RA may differ by patient, sex, country, and race. The present Mini Review introduces the current concept and unsolved problems of D2T RA, including the definition, prevalence, and factors contributing to D2T RA. We then discuss the management and therapeutic strategies for D2T RA. Finally, we explore a clinical approach to prevent patients from developing D2T RA.
Antimicrobial resistance and genomic characterization of Escherichia coli from pigs and chickens in Zhejiang, China
Authors: Zhou Wei , Lin Rumeng , Zhou Zhijin , Ma Jiangang , Lin Hui , Zheng Xue , Wang Jingge , Wu Jing , Dong Yuzhi , Jiang Han , Yang Hua , Yang Zhangnv , Tang Biao , Yue Min
Published: October 2022

Escherichia coli is considered an opportunistic pathogen and an indicator for antimicrobial resistance (AMR) monitoring. Despite many reports on its AMR monitoring, studies based on genome-based analysis of AMR genes are still insufficient. Here, 181 E. coli strains were isolated from anal swab samples collected from pigs and chickens of animal farms located in Eastern China and sequenced through the Illumina platform. The results showed that 87.85% (159/181) of the E. coli isolates were multidrug-resistant (MDR). Ampicillin (AMP)- spectinomycin (SPT)- tetracycline (TET)- florfenicol (FFC)- sulfisoxazole (SF)- trimethoprim/sulfamethoxazole (SXT) was the predominant AMR pattern. By whole-genome sequencing, we found that ST10 (10.49%, 19/181) and ST48 (7.18%, 13/181) were major sequence types. IncFIB and IncX1 were the most prevalent plasmid replicons. The AMR genes blaNDM-5 (1.10%, 2/181), mcr-1 (1.10%, 2/181), tet(X4) (1.10%, 2/181), and cfr (6.08%, 11/181) were also found in these isolates. In addition, among the 169 virulence genes detected, we identified astA (37.02%, 67/181), hlyA (1.66%, 3/181), hlyB (1.66%, 3/181) and hlyD (1.66%, 3/181), which were closely related to heat-stable enterotoxin 1 and α-hemolysin. In addition, there were 33 virulence genes associated with the iron uptake system, and 46 were adhesion-related genes. Our study highlighted the need for routine surveillance of AMR with advanced genomic approaches, providing up-to-date data on the prevalence of AMR for the development and execution of antimicrobial stewardship policy.
Distribution of two-component signal transduction systems BlpRH and ComDE across streptococcal species
Authors: Dhaked Hemendra Pal Singh , Biswas Indranil
Published: October 2022

Two-component signal transduction (TCS) systems are important regulatory pathways in streptococci. A typical TCS encodes a membrane-anchored sensor kinase (SK) and a cytoplasmic response regulator (RR). Approximately, 20 different types of TCSs are encoded by various streptococci. Among them, two TCSs, in particular BlpRH and ComDE, are required for bacteriocins production and competence development. The SK component of these two TCSs is highly similar and belongs to the protein kinase-10 (HPK-10) subfamily. While these two TCSs are present in streptococci, no systematic studies have been done to differentiate between these two TCSs, and the existence of these pathways in several species of the genus Streptococcus is also unknown. The lack of information about these pathways misguided researchers for decades into believing that the Streptococcus mutans BlpRH system is a ComDE system. Here, we have attempted to distinguish between the BlpRH and ComDE systems based on the location of the chromosome, genomic arrangement, and conserved residues. Using the SyntTax and NCBI databases, we investigated the presence of both TCS systems in the genome of several streptococcal species. We noticed that the NCBI database did not have proper annotations for these pathways in several species, and many of them were wrongly annotated, such as CitS or DpiB instead of BlpH. Nevertheless, our critical analyses led us to classify streptococci into two groups: class A (only the BlpRH system) and class B (both the BlpRH and ComDE systems). Most of the streptococcal groups, including bovis, pyogenic, mutans, salivarius, and suis, encode only the BlpRH system. In contrast, only in the mitis and anginosus groups were both the TCS systems present. The focus of this review is to identify and differentiate between the BlpRH and ComDE systems, and discuss these two pathways in various streptococci.
Engineered bacterial host for genetic encoding of physiologically stable protein nitration
Authors: Koch Nikolaj G. , Baumann Tobias , Nickling Jessica H. , Dziegielewski Anna , Budisa Nediljko
Published: October 2022

Across scales, many biological phenomena, such as protein folding or bioadhesion and cohesion, rely on synergistic effects of different amino acid side chains at multiple positions in the protein sequence. These are often fine-tuned by post-translational modifications that introduce additional chemical properties. Several PTMs can now be genetically encoded and precisely installed at single and multiple sites by genetic code expansion. Protein nitration is a PTM of particular interest because it has been associated with several diseases. However, even when these nitro groups are directly incorporated into proteins, they are often physiologically reduced during or shortly after protein production. We have solved this problem by using an engineered Escherichia coli host strain. Six genes that are associated with nitroreductase activity were removed from the genome in a simple and robust manner. The result is a bacterial expression host that can stably produce proteins and peptides containing nitro groups, especially when these are amenable to modification. To demonstrate the applicability of this strain, we used this host for several applications. One of these was the multisite incorporation of a photocaged 3,4-dihydroxyphenylalanine derivative into Elastin-Like Polypeptides. For this non-canonical amino acid and several other photocaged ncAAs, the nitro group is critical for photocleavability. Accordingly, our approach also enhances the production of biomolecules containing photocaged tyrosine in the form of ortho-nitrobenzyl-tyrosine. We envision our engineered host as an efficient tool for the production of custom designed proteins, peptides or biomaterials for various applications ranging from research in cell biology to large-scale production in biotechnology.
TREM2 improves neurological dysfunction and attenuates neuroinflammation, TLR signaling and neuronal apoptosis in the acute phase of intracerebral hemorrhage
Authors: Liu Sidan , Cao Xuezhao , Wu Zhe , Deng Shumin , Fu Hefei , Wang Yanzhe , Liu Fang
Published: October 2022

Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro. Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH.
Conversion of ER, PR, HER2 and Ki-67 and Prognosis in breast cancer metastases to the brain
Authors: Jiaxin Chen , Jinmei Zhou , Huiqiang Zhang , Xuexue Wu , Xiaobo Wang , Shaohua Zhang , Yanhong Tai , Zefei Jiang , Tao Wang
Published: October 2022

Objective

This study aimed to analyze the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index in the brain metastatic lesions and primary lesions in Chinese patients with breast cancer brain metastasis (BCBM) and determine the correlation between their changes and patients' survival.

Methods

A retrospective analysis was performed on patients with BCBM. The clinical characteristic of these patients was collected. The differences in the expression levels of the ER, PR, HER-2, and Ki-67 index between the primary lesions and brain lesions were evaluated, and the association between the differences and survival was analyzed.

Results

The conversion rate of anyone receptor (ER, PR, or HER2) between the primary lesions and brain metastatic lesions was 45.0% (18/40), of which the ER inconsistency rate was 25.0%, the PR inconsistency rate was 22.5%, and the HER-2 inconsistency rate was 15.0%, and the receptor conversion resulted in a subtype conversion of 27.5% (11/40). The patients with HER-2 expression discordance between the primary lesions and the brain metastatic lesions had significantly longer survival times (58.9 vs. 26.4 months, P = 0.04) after diagnosis of brain metastases.

Conclusion

In this study, 45.0% of breast cancer patients developed biomarker-conversion between the primary lesions and brain metastatic lesions, and the differences in the expression levels of the ER, PR, and HER-2, the change in Ki-67 index between the primary lesions and brain lesions may predict patients' survival.
The prognostic value of neutrophil-to-lymphocyte ratio in patients with traumatic brain injury: A systematic review
Authors: Ghozy Sherief , El-Qushayri Amr Ehab , Varney Joseph , Kacimi Salah Eddine Oussama , Bahbah Eshak I. , Morra Mostafa Ebraheem , Shah Jaffer , Kallmes Kevin M. , Abbas Alzhraa Salah , Elfil Mohamed , Alghamdi Badrah S. , Ashraf Ghulam , Alhabbab Rowa , Dmytriw Adam A.
Published: October 2022

Traumatic brain injury (TBI) places a heavy load on healthcare systems worldwide. Despite significant advancements in care, the TBI-related mortality is 30–50% and in most cases involves adolescents or young adults. Previous literature has suggested that neutrophil-to-lymphocyte ratio (NLR) may serve as a sensitive biomarker in predicting clinical outcomes following TBI. With conclusive evidence in this regard lacking, this study aimed to systematically review all original studies reporting the effectiveness of NLR as a predictor of TBI outcomes. A systematic search of eight databases was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA) recommendations. The risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) tool. Eight studies were ultimately included in the study. In most of the studies interrogated, severity outcomes were successfully predicted by NLR in both univariate and multivariate prediction models, in different follow-up durations up to 6 months. A high NLR at 24 and 48 h after TBI in pediatric patients was associated with worse clinical outcomes. On pooling the NLR values within studies assessing its association with the outcome severity (favorable or not), patients with favorable outcomes had 37% lower NLR values than those with unfavorable ones (RoM= 0.63; 95% CI = 0.44–0.88; p = 0.007). However, there were considerable heterogeneity in effect estimates (I2 = 99%; p < 0.001). Moreover, NLR was a useful indicator of mortality at both 6-month and 1-year intervals. In conjunction with clinical and radiographic parameters, NLR might be a useful, inexpensive marker in predicting clinical outcomes in patients with TBI. However, the considerable heterogeneity in current literature keeps it under investigation with further studies are warranted to confirm the reliability of NLR in predicting TBI outcomes.
Effects of dual-task training in patients with post-stroke cognitive impairment: A randomized controlled trial
Authors: Sun Ruifeng , Li Xiaoling , Zhu Ziman , Li Tiancong , Zhao Man , Mo Linhong , Li Wenshan , Xi Xiaoshuang , Huang Peiling , Gong Weijun
Published: October 2022

Background

Evidence for the efficacy of cognitive-motor dual-task (CMDT) training in patients with post-stroke cognitive impairment (PSCI) and no dementia is still lacking. More importantly, although some studies on the cognitive effect of CMDT training show an improvement in cognitive performance, the results are still controversial, and the intervention mechanism of CMDT training on cognitive function improvement is not clear. The main purpose of this study was to analyze the effects of CMDT training on cognitive function, neuron electrophysiology, and frontal lobe hemodynamics in patients with PSCI.

Methods

Here we tested the effects of CMDT training on cognitive function in PSCI patients. Forty subjects who met the criteria of PSCI were randomly assigned to control and experimental groups. CMDT training or cognitive task (CT) training was administered to each patient in the experimental and control groups, respectively. All subjects performed Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale before and after the intervention, and the event-related potentials (ERP) and functional near-infrared spectroscopy (fNIRS) were used to evaluate the changes in neuron electrophysiology and hemodynamics.

Results

Forty patients were randomized across Beijing Rehabilitation Hospital Capital Medical University in Beijing. At the end of the intervention, 33 subjects completed the experimental process. The CMDT group showed significant improvement in the MMSE (P = 0.01) and MoCA (P = 0.024) relative to the CT group. The results of ERP and fNIRS showed that CMDT training could shorten the latency of P300 (P = 0.001) and the peak time of oxygenated hemoglobin (P = 0.004). The results showed that CMDT training shortened the response time of central neurons and significantly increased the rate of oxygen supply to the frontal lobe.

Conclusion

CMDT training in patients with PSCI improved global cognitive function, which was supported by the improved neural efficiency of associated brain areas.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2000034862.
Autosomal dominant GDAP1 mutation with severe phenotype and respiratory involvement: A case report
Authors: Rodriguez-Hernandez Adrian , Mayo Meagan , Jauregui Lilibeth , Patel Pooja
Published: October 2022

Charcot Marie Tooth (CMT) is a heterogeneous group of genetic disorders characterized by progressive motor and sensory neuropathy. CMT is a multi-gene disorder with several possible mutations responsible for a wide range of clinical presentations. A specific mutation of the ganglioside-induced-differentiation-associated protein 1 (GDAP1) gene is associated with the axonal subtype of CMT (CMT2K) which is inherited in an autosomal dominant fashion, as well as the demyelinating subtype (CMT4A) which is inherited in an autosomal recessive pattern. Phenotypic disease expression is largely dependent on these inheritance patterns. While the autosomal recessive form (CMT4A) exhibits severe disease with an early onset, the autosomal dominant variant (CMT2K) tends to have milder phenotypes and a later onset. We describe an atypical presentation of a patient with severe CMT2K with rapidly progressive polyneuropathy, respiratory failure, and dysphonia. We suggest that this case will inspire further evaluation of disease heterogeneity and variants.
Case report: Acute ischemic stroke caused by intracranial artery dissection in a patient with skull fractures
Authors: Zheng Bo , Luo XiaoLan , Zhou JiangHao , Huang XueQiong , Li MaoXia , Zheng Hui , Yuan YiPing , Wang Jian
Published: October 2022

The intracranial artery dissection (IAD) is an uncommon but life-threatening disease. The IAD would develop a significant cerebral infarction due to unrecognized contrecoup brain injury. We report a 53-year-old man fell to develop blunt cerebrovascular injuries (BCVIs) more than 2 months ago. During his rehabilitation, he often had a transient left headache and underwent short-term right limb weakness twice, but he did not care. He was hospitalized again because of suffering right limb weakness for more than 4 h. The brain computed tomography angiography (CTA) showed subtotal occlusion of the left middle cerebral artery M1 segment, and the vascular morphology displayed the IAD. The patient was then treated with balloon dilation and a self-expanding stent. This case highlights that IAD may show delayed onset with no initial typical symptom. By early detecting of abnormal signs and symptoms, serious traumatic brain injury may be avoided.
Effect of garlic extract on weight loss and gut microbiota composition in obese women: A double-blind randomized controlled trial
Authors: Ettehad-Marvasti Fateme , Ejtahed Hanieh-Sadat , Siadat Seyed-Davar , Soroush Ahmad-Reza , Hoseini-Tavassol Zahra , Hasani-Ranjbar Shirin , Larijani Bagher
Published: October 2022

Objective

From a nutritional perspective, garlic extract could be a prebiotic product, which is useful for obese subjects, and one of its health-promoting underlying mechanisms is modulating gut microbiota composition. In this randomized double-blind clinical trial, the goal was to determine the effect of Allium (garlic extract) on anthropometric indices and gut microbiota composition in obese women following a low-calorie diet.

Materials and methods

Forty-three obese women were randomly divided into garlic extract (400 mg Allium sativum powder containing 1,100 mcg allicin/tablet) or placebo groups. During the 2 months of the study, each participant took two tablets per day. At the beginning and at the end of the clinical trial, anthropometric measurements were done and blood and fecal samples were collected. We evaluated the gut microbiota composition using quantitative real-time PCR.

Results

In total, 16 subjects in each group completed the 2-month trial. Allium and placebo groups’ participants had mean ages of 37.8 ± 7.4 and 34.2 ± 6.8 years, respectively (P > 0.05). Baseline body mass index (BMI) was significantly different between groups, subjects in the placebo group had lower BMI compared with the Allium group (P < 0.05). Allium and placebo caused a 1.7% and 2.7% decrease in BMI from the baseline values, respectively (P < 0.01). Fasting insulin level significantly decreased in the both groups (P < 0.01). Level of homeostasis model assessment of insulin resistance (HOMA-IR) has decreased significantly in the Allium group (P = 0.007). The frequency of Akkermansia had decreasing trend while the abundance of Faecalibacterium and Bifidobacterium showed increasing trend in the Allium group.

Conclusion

In the both groups, a decrease in BMI and other anthropometric indices has been observed. Despite weight loss after following a low-calorie diet and taking Allium, slight changes have been shown in the composition of gut microbiota in obese women.

Trial registration

This trial was registered in the Iranian Registry of Clinical Trials (IRCT) (code: IRCT090420001825N2).
A highly sensitive lateral flow immunoassay for the rapid and on-site detection of enrofloxacin in milk
Authors: Alhammadi Munirah , Yoo Jingon , Sonwal Sonam , Park So Young , Umapathi Reddicherla , Oh Mi-Hwa , Huh Yun Suk
Published: October 2022

Enrofloxacin (ENR) is a veterinary antibiotic used to treat bacterial infections in livestock. It chiefly persists in foods and dairy products, which in turn pose severe risks to human health. Hence it is very important to detect the ENR in foods and dairy products to safeguard human health. Herein, we attempted to develop a single-step detection lateral flow immunochromatographic assay (LFIA) using gold nanoparticles (AuNPs) for the rapid and on-site detection of ENR in milk samples. An anti-enrofloxacin monoclonal antibody (ENR-Ab) was conjugated with AuNPs for the specific detection of ENR in milk samples. For sensitivity improvement, many optimization steps were conducted on LFIA test strips. The visual limit of detection (vLOD) was found to be 20 ng/ml with a cut-off value of 50 ng/ml in the milk samples. The obtained LOD and cut-off value were within the safety limit guidelines of the Ministry of food and drug safety, South Korea. The test strip showed negligible cross-reactivity with ENR analogs, and other components of antibiotics, this indicates the high specificity of the LFIA test strip towards ENR. The designed test strip showed good reliability. The visual test results can be seen within 10 min without the need for special equipment. Therefore, the test strip can be employed as a potential detection strategy for the qualitative on-site detection of enrofloxacin in milk samples.
Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index
Authors: Huang Benjamin , Huang Weiting , Allen John Carson , Sun Lijuan , Goh Hui Jen , Kong Siew Ching , Lee Dewaine , Ding Cherlyn , Bosco Nabil , Egli Leonie , Actis-Goretta Lucas , Magkos Faidon , Arigoni Fabrizio , Leow Melvin Khee-Shing , Tan Swee Yaw , Yeo Khung Keong
Published: October 2022

Background

Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals.

Methods

A cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores.

Results

Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588–0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness.

Conclusions

The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.