bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic alterations impair differentiation and effector functions of CD8+ T cells
Authors: Bensussen Antonio , Santana Maria Angelica , Rodríguez-Jorge Otoniel
Published: August 2022

CD8+ T lymphocytes are one of the main effector cells of the immune system, they protect the organism against intracellular threats such as viruses and bacteria, as well as neoplasms. It is currently well established that CD8+ T cells have distinct immune responses, given by their phenotypes Tc1, Tc2, Tc17, and TcReg. The cellular plasticity of such phenotypes depends on the presence of different combinations of cytokines in the extracellular medium. It is known that metabolic imbalances play an important role in immune response, but the precise role of metabolic disturbances on the differentiation and function of CD8+ T cells, however, has not been explored. In this work, we used a computational model to explore the potential effect of metabolic alterations such as hyperglycemia, high alcohol consumption, dyslipidemia, and diabetes on CD8+ T cell differentiation. Our model predicts that metabolic alterations preclude the effector function of all CD8+ T cell phenotypes except for TcReg cells. It also suggests that such inhibition originates from the increase of reactive oxygen species in response to metabolic stressors. Finally, we simulated the outcome of treating metabolic-inhibited CD8+ T cells with drugs targeting key molecules such as mTORC1, mTORC2, Akt, and others. We found that overstimulation of mTORC2 may restore cell differentiation and functions of all effector phenotypes, even in diabetic patients. These findings highlight the importance of our predictive model to find potential targets to strengthen immunosuppressed patients in chronic diseases, like diabetes.
T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation
Authors: Cammann Clemens , Israel Nicole , Frentzel Sarah , Jeron Andreas , Topfstedt Eylin , Schüler Thomas , Simeoni Luca , Zenker Martin , Fehling Hans Joerg , Schraven Burkhart , Bruder Dunja , Seifert Ulrike
Published: August 2022

Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1,Ptpn6) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2,Ptpn11) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate. Here, we analyzed the role of the constitutively active SHP2-D61Y-mutant in T cell activation using knock-in mice expressing the mutant formPtpn11D61Yin T cells. We observed reduced numbers of CD8+and increased numbers of CD4+T cells in the bone marrow and spleen of young and aged SHP2-D61Y-mutant mice as well as in Influenza A Virus (IAV)-infected mice compared to controls. In addition, we found elevated frequencies of effector memory CD8+T cells and an upregulation of the programmed cell death protein 1 (PD-1)-receptor on both CD4+and CD8+T cells. Functional analysis of SHP2-D61Y-mutated T cells revealed an induction of late apoptosis/necrosis, a reduced proliferation and altered signaling upon TCR stimulation. However, the ability of D61Y-mutant mice to clear viral infection was not affected. In conclusion, our data indicate an important regulatory role of SHP2 in T cell function, where the effect is determined by the kinetics of SHP2 phosphatase activity and differs in the presence of the permanently active and the temporally regulated phosphatase. Due to interaction of SHP2 with the PD-1-receptor targeting the protein-tyrosine phosphatase might be a valuable tool to enhance T cell activities in immunotherapy.
Signaling networks controlling ID and E protein activity in T cell differentiation and function
Authors: Hwang Sung-Min , Im Sin-Hyeog , Rudra Dipayan
Published: August 2022

E and inhibitor of DNA binding (ID) proteins are involved in various cellular developmental processes and effector activities in T cells. Recent findings indicate that E and ID proteins are not only responsible for regulating thymic T cell development but also modulate the differentiation, function, and fate of peripheral T cells in multiple immune compartments. Based on the well-established E and ID protein axis (E-ID axis), it has been recognized that ID proteins interfere with the dimerization of E proteins, thus restricting their transcriptional activities. Given this close molecular relationship, the extent of expression or stability of these two protein families can dynamically affect the expression of specific target genes involved in multiple aspects of T cell biology. Therefore, it is essential to understand the endogenous proteins or extrinsic signaling pathways that can influence the dynamics of the E-ID axis in a cell-specific and context-dependent manner. Here, we provide an overview of E and ID proteins and the functional outcomes of the E-ID axis in the activation and function of multiple peripheral T cell subsets, including effector and memory T cell populations. Further, we review the mechanisms by which endogenous proteins and signaling pathways alter the E-ID axis in various T cell subsets influencing T cell function and fate at steady-state and in pathological settings. A comprehensive understanding of the functions of E and ID proteins in T cell biology can be instrumental in T cell-specific targeting of the E-ID axis to develop novel therapeutic modalities in the context of autoimmunity and cancer.
Transcriptomic analysis of adaptive mechanisms in response to inland saline-alkaline water in the mud crab, Scylla paramamosain
Authors: Liang Guoling , Qin Kangxiang , Chen Yuhao , Niu Mingming , Wang Huan , Wang Chunlin , Mu Changkao , Chen Lizhi , Wang Fangfang , Su Qiong , Zhu Ritong
Published: August 2022

Scylla paramamosain is an important marine aquaculture crustacean on the southeastern coast of China. Given the difficulties of overcrowded coastal aquaculture space and insufficient production, inland saline-alkaline water culture has the potential to alleviate this bottleneck. This study separated 600 crabs into four groups: normal salinity (12-18 ppt, NS), coastal low salinity (3-5 ppt, CS), inland low salinity saline-alkaline (1.5 ppt, IS), and acute low salinity (23 ppt down to 3 ppt, AS), followed by a transcriptomic analysis of the gills. CS-vs-NS, IS-vs-NS, and AS-vs-NS obtained 1154, 1012, and 707 DEGs, respectively. GO analysis showed that the DEGs of the three comparison groups were mainly involved in cellular process, metabolic process, biological regulation, organelle, membrane, extracellular region, binding, and catalytic activity. The findings demonstrate that a significant number of genes are engaged in controlling metabolic processes in the osmoregulation process, and that cell membrane catalysis and different enzymes play a vital part in the environmental adaption process. KEGG enrichment analysis revealed that IS possesses a considerable number of signaling pathways that play important roles in osmoregulation when compared to NS. The cAMP signaling pathway increased the expression of CaM and Na+/K+-ATPase. These findings show that cations like Ca2+, Na+, and K+ are critical for S. paramamosain to adapt to inland low salinity saline-alkaline water, and that the cAMP signaling pathway regulates their levels. This research provides a theoretical foundation for improving the saline-alkaline aquaculture technology of S. paramamosain.
Diagnostic accuracy of SARS-CoV-2 Panbio™ rapid antigen diagnostic tests in a 4,440-case clinical follow-up
Authors: Hamar Ágoston , Filipánits Kristóf , Váradi Alex , Váradi-Rácz Rita , Gellén Henrietta Orsolya , Futács Krisztina , Urbán Péter , Kovacs Gabor L. , Gombos Katalin
Published: August 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Rapid Antigen Detection Testing (RADT) has been subjected to several evaluations in reference to diagnostic accuracy, ranging from small scale up to large population studies including nation-wide community-based studies. All confirmed the diagnostic accuracy of the tests which were strongly dependent upon the infection's population prevalence. In our retrospective study, parallel SARS-CoV-2 Panbio™ RADT assay, including real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests, were aimed to evaluate diagnostic performance regarding the rapid antigen diagnostic testing. Out of 4,440 paired tests, 609 samples tested positive using RT-qPCR, resulting in a prevalence of 13.7%. Panbio detected 251 (5.7%) positive tested samples. Overall sensitivity was 41.2% (95% CI 37.4–45.2%) and overall specificity was 99.7% (95% CI 99.4–99.8%). Positive predictive value (PPV) was 95.1% (95% CI 91.8–97.1%) and the negative predictive value (NPV) was 91.4% (95% CI 90.5–92.2%). RADT sensitivity increased with stratification in reference to the results according to PCR Cycle threshold (Ct) and presence of the symptoms considerably influenced PPV and NPV. Sensitivity in the group of Ct values ≤ 20 was 91.2%, 68.6% within the Ct range of 20–25, 47.9% in the group of Ct values between 25 and 30, and 12.6% in the group of Ct values between 30 and 35. A follow-up of the positive cases aligned with RT-qPCR testing and comparison of the general population enrolled in the testing in which the fatal cases occurred enabled us to estimate real clinical diagnostic performance regarding the SARS-CoV-2 Panbio RADT. Based upon our results, we recommend the SARS-CoV-2 Panbio RADT tests be carried out as the primary test, without parallel PCR testing, only among high population prevalence rates of the infection and to be used for symptomatic individuals with average or low severe disease developmental risk. In the case of high risk regarding the development of severe infection complications, a parallel SARS-CoV-2 RT-qPCR is needed to be carried out to attain proper diagnostic accuracy and avoid delaying appropriate medical care.
Metagenomic next-generation sequencing-guided antimicrobial treatment versus conventional antimicrobial treatment in early severe community-acquired pneumonia among immunocompromised patients (MATESHIP): A study protocol
Authors: Fan Shaohua , Si Min , Xu Nana , Yan Meichen , Pang Mingmin , Liu Guangfeng , Gong Jibin , Wang Hao
Published: August 2022

Background

Severe community-acquired pneumonia (SCAP) is the main cause of mortality in immunocompromised patients. Compared with conventional microbiological tests (CMT), metagenomic next-generation sequencing (mNGS) can quickly and simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased manner. It is increasingly used for severe respiratory infectious diseases, especially for immunocompromised patients. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes in immunocompromised patients with SCAP have not been evaluated.

Methods/Design

The MATESHIP study is a prospective, multicenter, parallel-group, open-label, randomized controlled trial from 20 ICUs in university hospitals and academic teaching hospitals across Shandong Province, China. We will enroll 342 immunocompromised patients with early onset SCAP who are admitted to an intensive care unit (ICU). Participants will be randomly allocated to an mNGS-guided treatment group or a conventional treatment group (guided by CMT), according to centrally computer-based block randomization stratified by participating centers. Participants will undergo CMT tests using appropriate lower respiratory tract (LRT) and other necessary specimens, with or without mNGS tests using LRT specimens. The primary outcomes will be: (1) The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death; and (2) the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses). The secondary outcome measures will be: days from randomization to initiation of definitive antimicrobial treatment; overall antimicrobial agent use and cost; total cost of hospitalization; length of ICU stay; 28- and 90-day mortality; and clinical cure rate. This study hypothesizes that mNGS-guided treatment will decrease the degree of organ dysfunction/failure, the consumption of antimicrobial agents, and mortality, while the cure rate will be increased, and the time to initiation of appropriate therapy will be advanced.

Discussion

The MATESHIP study will evaluate for the first time whether mNGS-guided antimicrobial therapy improves the outcomes of SCAP in an immunocompromised population, and provide high-level evidence on the application of mNGS in the management of this population.

Clinical Trial Registration

[ClinicalTrials.gov], identifier [NCT05290454].
Comprehensive deciphering prophages in genus Acetobacter on the ecology, genomic features, toxin–antitoxin system, and linkage with CRISPR-Cas system
Authors: Qian Chenggong , Ma Jiawen , Liang Jiale , Zhang Lei , Liang Xinle
Published: August 2022

Acetobacter is the predominant microbe in vinegar production, particularly in those natural fermentations that are achieved by complex microbial communities. Co-evolution of prophages with Acetobacter, including integration, release, and dissemination, heavily affects the genome stability and production performance of industrial strains. However, little has been discussed yet about prophages in Acetobacter. Here, prophage prediction analysis using 148 available genomes from 34 Acetobacter species was carried out. In addition, the type II toxin–antitoxin systems (TAs) and CRISPR-Cas systems encoded by prophages or the chromosome were analyzed. Totally, 12,000 prophage fragments were found, of which 350 putatively active prophages were identified in 86.5% of the selected genomes. Most of the active prophages (83.4%) belonged to the order Caudovirales dominated by the families Siphoviridae and Myroviridae prophages (71.4%). Notably, Acetobacter strains survived in complex environments that frequently carried multiple prophages compared with that in restricted habits. Acetobacter prophages showed high genome diversity and horizontal gene transfer across different bacterial species by genomic feature characterization, average nucleotide identity (ANI), and gene structure visualization analyses. About 31.14% of prophages carry type II TAS, suggesting its important role in addiction, bacterial defense, and growth-associated bioprocesses to prophages and hosts. Intriguingly, the genes coding for Cse1, Cse2, Cse3, Cse4, and Cas5e involved in type I-E and Csy4 involved in type I-F CRISPR arrays were firstly found in two prophages. Type II-C CRISPR-Cas system existed only in Acetobacter aceti, while the other Acetobacter species harbored the intact or eroded type I CRISPR-Cas systems. Totally, the results of this study provide fundamental clues for future studies on the role of prophages in the cell physiology and environmental behavior of Acetobacter.
Contribution of omics to biopreservation: Toward food microbiome engineering
Authors: Borges Frédéric , Briandet Romain , Callon Cécile , Champomier-Vergès Marie-Christine , Christieans Souad , Chuzeville Sarah , Denis Catherine , Desmasures Nathalie , Desmonts Marie-Hélène , Feurer Carole , Leroi Françoise , Leroy Sabine , Mounier Jérôme , Passerini Delphine , Pilet Marie-France , Schlusselhuber Margot , Stahl Valérie , Strub Caroline , Talon Régine , Zagorec Monique
Published: August 2022

Biopreservation is a sustainable approach to improve food safety and maintain or extend food shelf life by using beneficial microorganisms or their metabolites. Over the past 20 years, omics techniques have revolutionised food microbiology including biopreservation. A range of methods including genomics, transcriptomics, proteomics, metabolomics and meta-omics derivatives have highlighted the potential of biopreservation to improve the microbial safety of various foods. This review shows how these approaches have contributed to the selection of biopreservation agents, to a better understanding of the mechanisms of action and of their efficiency and impact within the food ecosystem. It also presents the potential of combining omics with complementary approaches to take into account better the complexity of food microbiomes at multiple scales, from the cell to the community levels, and their spatial, physicochemical and microbiological heterogeneity. The latest advances in biopreservation through omics have emphasised the importance of considering food as a complex and dynamic microbiome that requires integrated engineering strategies to increase the rate of innovation production in order to meet the safety, environmental and economic challenges of the agri-food sector.
An efficient anoxic/aerobic/aerobic/anoxic process for domestic sewage treatment: From feasibility to application
Authors: Wang Yao , Liang Baorui , Kang Fei , Wang Youzhao , Zhao Chaoyue , Lyu Zhenning , Zhu Tong , Zhang Zhijun
Published: August 2022

In this paper, the anoxic/aerobic/aerobic/anoxic (AOOA) process was proposed using fixed biofilms in a continuous plug-flow multi-chamber reactor, and no sludge reflux operation was performed during the 190 days of operation. The reactor volume ratio of 1.5:2:1.5:1 (A/O/O/A) with the dissolved oxygen (DO) concentration of 2 mg L−1 in the aerobic zone was the optimal condition for reactor operation. According to the results obtained from the treatment of real domestic sewage, when the hydraulic retention time (HRT) was 6 h, the effluent of the reactor could meet the discharge standard even in cold conditions (13°C). Specifically, the elemental-sulfur-based autotrophic denitrification (ESAD) process contributed the most to the removal of total inorganic nitrogen (TIN) in the reactor. In addition, the use of vibration method was helpful in removing excess sludge from the biofilms of the reactor. Overall, the AOOA process is an efficient and convenient method for treating domestic sewage.
Development of a system to analyze oral frailty associated with Alzheimer's disease using a mouse model
Authors: Kuramoto Eriko , Kitawaki Ayano , Yagi Takakazu , Kono Hiroshi , Matsumoto Shin-Ei , Hara Hiromitsu , Ohyagi Yasumasa , Iwai Haruki , Yamanaka Atsushi , Goto Tetsuya
Published: August 2022

The rapid aging of the population makes the detection and prevention of frailty increasingly important. Oral frailty has been proposed as a novel frailty phenotype and is defined as a decrease in oral function coexisting with a decline in cognitive and physical functions. Oral frailty has received particular attention in relation to Alzheimer's disease (AD). However, the pathomechanisms of oral frailty related to AD remain unknown. It is assumed that the mesencephalic trigeminal nucleus (Vmes), which controls mastication, is affected by AD pathology, and as a result, masticatory function may be impaired. To investigate this possibility, we included male 3 × Tg-AD mice and their non-transgenic counterpart (NonTg) of 3–4 months of age in the present study. Immunohistochemistry revealed amyloid-β deposition and excessive tau phosphorylation in the Vmes of 3 × Tg-AD mice. Furthermore, vesicular glutamate transporter 1-immunopositive axon varicosities, which are derived from Vmes neurons, were significantly reduced in the trigeminal motor nucleus of 3 × Tg-AD mice. To investigate whether the AD pathology observed in the Vmes affects masticatory function, we analyzed electromyography of the masseter muscle during feeding. The 3 × Tg-AD mice showed a significant delay in masticatory rhythm compared to NonTg mice. Furthermore, we developed a system to simultaneously record bite force and electromyography of masseter, and devised a new method to estimate bite force during food chewing in mice. Since the muscle activity of the masseter showed a high correlation with bite force, it could be accurately estimated from the muscle activity. The estimated bite force of 3 × Tg-AD mice eating sunflower seeds was predominantly smaller than that of NonTg mice. However, there was no difference in masseter weight or muscle fiber cross-sectional area between the two groups, suggesting that the decreased bite force and delayed mastication rhythm observed in 3 × Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3 × Tg-AD mice was most likely caused by AD pathology in the Vmes. Thus, novel quantitative analyses of masticatory function using the mouse model of AD enabled a comprehensive understanding of oral frailty pathogenesis.
Changes in working memory performance and cortical activity during acute aerobic exercise in young adults
Authors: Zheng Kefeng , Deng Zhangyan , Qian Jiali , Chen Yanxia , Li Shiyuan , Huang Tao
Published: August 2022

This study aimed to examine the concurrent performance of working memory and cortical activity during acute aerobic exercise in young adults. In a crossover study design, 27 young adults (mean age = 22.7 ± 3.4 years, 15 women) participated in two experimental conditions in a randomized order: (1) sitting condition (without exercise) and (2) cycling condition (moderate-intensity exercise). Working memory was measured with a modified version of the n-back task. A functional near-infrared spectroscopy (fNIRS) was used to measure cortex activation. In the cycling condition, response time (RT) for the n-back task was significantly faster (p < 0.05). No differences in accuracy were observed between the sitting and cycling conditions. The fNIRS results showed that the oxygenated hemoglobin (oxy-Hb) concentrations in the bilateral frontopolar area (p < 0.05), dorsolateral prefrontal cortex (p < 0.05), and right premotor and supplementary cortex (p < 0.05) were decreased while cycling. The findings indicated that the concurrent performance of working memory was improved during acute aerobic exercise, whereas cortical activity was decreased in some brain regions.
Relationship between the mean of 24-h venous blood glucose and in-hospital mortality among patients with subarachnoid hemorrhage: A matched cohort study
Authors: Wang Jun-Hong , Li Hua , Yang Hong-Kuan , Chen Ru-Dong , Yu Jia-Sheng
Published: August 2022

Objective

The aim of this study was to explore the correlation between the mean of 24-h venous blood glucose (BG) and in-hospital mortality and all-cause mortality (ACM) in patients with subarachnoid hemorrhage (SAH).

Methods

Detailed clinical information was acquired from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The best cutoff value of mean BG was calculated using the X-tile program. Univariate and multivariate logistic regressive analyses were utilized to analyze the prognosis significance of mean BG, and survival curves were drawn using the Kaplan-Meier (K-M) approach. To improve the reliability of results and balance the impact of underlying confounders, the 1:1 propensity score matching (PSM) approach was utilized.

Results

An overall of 1,230 subjects were selected herein. The optimal cutoff value of the mean BG for in-hospital mortality was 152.25. In addition, 367 pairs of score-matched subjects were acquired after PSM analysis, and nearly all variables' differences were balanced. K-M analysis showed that patients with mean BG ≥ 152.25 mg/dl had significantly higher in-hospital, 3-month, and 6-month mortalities compared with patients with mean BG < 152.25 mg/dl (p < 0.001). The multivariable logistic regressive analyses revealed that patients with mean BG ≥ 152.25 mg/dl had significantly increased in-hospital mortality compared with patients with mean BG < 152.25 mg/dl after the adjustment for possible confounders (OR = 1.994, 95% CI: 1.321–3.012, p = 0.001). Similar outcomes were discovered in the PSM cohort.

Conclusion

Our data suggested that mean BG was related to ACM of patients with SAH. More studies are needed to further analyze the role of the mean of 24-h venous BG in patients with SAH.
Xper-CT combined with laser-assisted navigation radiofrequency thermocoagulation in the treatment of trigeminal neuralgia
Authors: Xiong Fengzhen , Zhang Tao , Wang Qingbo , Li Chenglong , Geng Xin , Wei Qi , Yuan Zhengbo , Li Zefu
Published: August 2022

Objective

Our objective was to study the clinical feasibility of Xper-CT combined with laser-assisted radiofrequency thermocoagulation in the treatment of trigeminal neuralgia.

Materials and methods

A retrospective analysis was made of 60 patients with trigeminal neuralgia who visited the Affiliated Hospital of Binzhou Medical University from January 2019 to May 2021. According to the different surgical methods, we were divided into C-arm X-ray group and laser navigation group. The operation time, operative complications, post-operative 24 h, post-operative 3 and 6 months Barrow Neurotics Institute (BNI) score were recorded and compared.

Results

Compared with the C-arm X-ray-guided puncture group, Xper-CT combined with laser-assisted navigation has the obvious advantages of shorter total puncture time, shorter surgical time, higher success rate of first puncture, and better surgical effect.

Conclusion

Radiofrequency therapy of trigeminal neuralgia with Xper-CT combined with laser-assisted navigation has a good clinical effect and can be promoted and applied.
Magnetic Resonance Imaging Findings of Intraspinal Tuberculoma in Children
Authors: Zhou Yirui , Qin Yong , Mu Tong , Zheng Helin , Cai Jinhua
Published: August 2022

Background and Purpose

Intraspinal tuberculoma is a rare disease in children, and its imaging findings have been described in only a few case reports. This study aimed to investigate the magnetic resonance imaging (MRI) features of pediatric intraspinal tuberculoma and to explore the possible pathogenesis of the disease.

Materials and Methods

The clinical and MRI data of 24 child patients with intraspinal tuberculoma (such as 6 cases of intramedullary tuberculoma, 8 cases of intradural extramedullary tuberculoma, and 10 cases of epidural tuberculoma) were retrospectively analyzed. All patients underwent plain and contrast-enhanced MR scans. The diagnosis was confirmed by surgical pathology or by antituberculous treatment and follow-up data.

Results

Intramedullary tuberculoma had a round shape, while intradural extramedullary tuberculoma and epidural tuberculoma presented long-fusiform or en plaque shapes. Regarding MRI signals, intramedullary tuberculoma and extramedullary tuberculoma were mainly isointense on T1-weighted imaging (T1WI) and hypointense or isointense on T2WI. Rim enhancement was observed in intramedullary tuberculoma, and marked homogeneous enhancement was dominant in extramedullary tuberculoma. Ten (10/24) tuberculomas occurred during antituberculous therapy, with intradural extramedullary tuberculoma accounting for 7 cases (7/8), which was significantly more frequent than intramedullary tuberculoma (1/6) or epidural tuberculoma (2/10).

Conclusion

MRI is important in the diagnosis of intraspinal tuberculoma, which is characterized by isointensity on T1WI, isointensity, or hypointensity on T2WI, and rim or obvious homogeneous enhancement. Some intraspinal tuberculomas, especially intradural extramedullary tuberculomas, might be associated with the “paradoxical response” mechanism during the tuberculosis treatment.
Association between serum 25-hydroxyvitamin d and myeloperoxidase: A cross-sectional study of a general population in China
Authors: Zhou Junteng , Li Ruicen , Bao Ting , Jiang Wei , Huang Yan
Published: August 2022

Background

Several studies have found a strong association between cardiovascular diseases and myeloperoxidase (MPO) as a marker of oxidative stress. Although the anti-inflammatory effects of vitamin D in adults have been validated, evidence about the relationship between MPO and 25(OH)D is lacking. This study aimed to investigate the relationship between MPO and 25(OH)D in the general Chinese population.

Methods

From November 2018 to August 2019, a total of 6414 subjects were enrolled in a tertiary referral hospital in China, which included 3,122 women and 3,292 men. The dependent and independent variables were MPO and 25(OH)D, respectively. The confounders included age, sex, body mass index, waist-hip ratio, smoking status, alcohol drinking status, calcium, and parathyroid hormone concentration.

Results

In the fully adjusted model, we found that MPO decreased by 0.12 (95% CI −0.16, −0.08), ng/mL for each unit (1 nmol/L) increase in 25(OH)D. When 25(OH) D was divided into quartiles, compared with Q1 (< 41.4 nmol/L), the adjusted beta coefficients (β) of MPO in Q2–Q4 were −2.29 (95% CI, −4.31 to −0.27), −4.76 (95% CI, −6.83 to −2.69), and −6.07 (95% CI, −8.23 to −3.92), respectively (P for the trend < 0.0001). When 25(OH) D was divided according to clinical severity, compared with the severely deficient (< 30 nmol/L) s≥ 30, < 50 nmol/L) and sufficient groups (≥ 50 nmol/L) were −2.59 (95% CI, −5.87 to 0.69) and −5.87 (95% CI, −9.17 to −2.57), respectively (P for the trend < 0.0001).

Conclusion

After adjusting for age, sex, BMI, waist-hip ratio, smoking status, alcohol status, calcium, and PTH, circulating 25(OH)D was negatively associated with MPO.
Id2 exerts tumor suppressor properties in lung cancer through its effects on cancer cell invasion and migration
Authors: Chen Jian-Ting , Hsu Yuan-Ling , Hsu Yi-Chiung , Tseng Yi-Hsin , Liu Ming-Han , Weng Chia-Wei , Lin Ching-Hao , Pan Szu-Hua , Chen Jeremy J.W. , Wang Chi-Chung
Published: August 2022

Background

Despite advances in prognosis and treatment of lung adenocarcinoma (LADC), a notable non–small cell lung cancer subtype, patient outcomes are still unsatisfactory. New insight on novel therapeutic strategies for LADC may be gained from a more comprehensive understanding of cancer progression mechanisms. Such strategies could reduce the mortality and morbidity of patients with LADC. In our previous study, we performed cDNA microarray screening and found an inverse relationship between inhibitor of DNA binding 2 (Id2) expression levels and the invasiveness of LADC cells.

Materials and Methods

To identify the functional roles of Id2 and its action mechanisms in LADC progression, we successfully established several Id2-overexpressing and Id2-silenced LADC cell clones. Subsequently, we examined in vitro the effects exerted by Id2 on cell morphology, proliferation, colony formation, invasive, and migratory activities and examined in vivo those exerted by Id2 on cell metastasis. The mechanisms underlying the action of Id2 were investigated using RNA-seq and pathway analyses. Furthermore, the correlations of Id2 with its target gene expression and clinical outcomes were calculated.

Results

Our data revealed that Id2 overexpression could inhibit LADC cells’ migratory, invasive, proliferation, and colony formation capabilities. Silencing Id2 expression in LADC cells reversed the aforementioned inhibitory effects, and knockdown of Id2 increased LADC cells’ metastatic abilities in vivo. Bioinformatics analysis revealed that these effects of Id2 on cancer progression might be regulated by focal adhesion kinase (FAK) signaling and CD44/Twist expression. Furthermore, in online clinical database analysis, patients with LADC whose Id2 expression levels were high and FAK/Twist expression levels were low had superior clinical outcomes.

Conclusion

Our data indicate that the Id2 gene may act as a metastasis suppressor and provide new insights into LADC progression and therapy.
A novel defined m7G regulator signature to investigate the association between molecular characterization and clinical significance in lung adenocarcinoma
Authors: Dong Yi , Li Yingge , Yao Yi , Song Qibin
Published: August 2022

Background

About170 chemical modifications to RNAs have been identified, which significantly affect gene expression. Dysregulation of RNA modifications induced by abnormal expression or mutations in RNA modifiers might result in cancer. The most frequent RNA modifications are N6-methyladenosine (m6A), 5-methylcytosine (m5C), and N7-methylguanosine (m7G). Lung cancer is the leading cause of cancer-related deaths globally. The present study aimed to investigate whether the expression of the m7G-related genes is linked to lung cancer cases with lung adenocarcinoma (LUAD), which accounts for about 40% of lung cancer cases.

Methods

A total of 12 m7G-related differentially expressed genes (DEGs) were identified in LUAD patients by The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) Cox regression method was used to build a four-gene risk model. Then, LUAD patients in the TCGA cohort were divided into low- and high-risk groups based on their risk scores for subsequent molecular and clinical research.

Results

Compared to the low-risk group, the high-risk group had a decreased overall survival (OS) (P=0.047). The risk score and stage were independent factors for predicting the OS of LUAD (P=0.0004 and P<0.0001, respectively). Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses based on the two groups showed that the DEGs were metabolically and hormonally related. The high-risk group showed a higher mutation rate and lesser immune cell infiltration, especially in TP53, KRAS, and MET. The expression level of PD-L1 and CTLA4 was high in the high-risk group (P<0.05). The high-risk group is more sensitive to anti-cancer therapy with lower IC50 and higher immunophenoscore (IPS).

Conclusions

In this study, we developed a novel LUAD stratification model based on m7G-related genes that successfully predicts the prognosis of LUAD patients and serves as a guide for clinically personalized treatment.
Progressive multifocal leukoencephalopathy associated with chemotherapy induced lymphocytopenia in solid tumors – case report of an underestimated complication
Authors: Mayr Patrick , Lutz Mathias , Schmutz Maximilian , Hoeppner Jens , Liesche-Starnecker Friederike , Schlegel Jürgen , Gaedcke Jochen , Claus Rainer
Published: August 2022

Background

JC virus reactivation causing progressive multifocal leukoencephalopathy (PML) occurs preferentially in human immunodeficiency virus (HIV) positive individuals or patients suffering from hematologic neoplasms due to impaired viral control. Reactivation in patients suffering from solid malignancies is rarely described in published literature.

Case Presentation

Here we describe a case of PML in a male patient suffering from esophageal cancer who underwent neoadjuvant radiochemotherapy and surgical resection in curative intent resulting in complete tumor remission. The radiochemotherapy regimen contained carboplatin and paclitaxel (CROSS protocol). Since therapy onset, the patient presented with persistent and progredient leukopenia and lymphopenia in absence of otherwise known risk factors for PML. Symptom onset, which comprised aphasia, word finding disorder, and paresis, was apparent 7 months after therapy initiation. There was no relief in symptoms despite standard of care PML directed supportive therapy. The patient died two months after therapy onset.

Conclusion

PML is a very rare event in solid tumors without obvious states of immununosuppression and thus harbors the risk of unawareness. The reported patient suffered from lymphopenia, associated with systemic therapy, but was an otherwise immunocompetent individual. In case of neurologic impairment in patients suffering from leukopenia, PML must be considered – even in the absence of hematologic neoplasia or HIV infection.
Clinicopathologic study of mantle cell lymphoma with epstein-barr virus infection: A case series and literature review
Authors: Li Xiaoju , Zhou Fanlin , Li Shijie , Wang Yangyang , Fan Jianing , Liang Xiao , Peng Yan , Jin Yudi , Jiang Weiyang , Liu Fang , Zhou Yixing , Liu Shuke , Wang Tao , Peng Yi , Xiong Jianbo , Liu Jia , Zhang Jing , He Changqing , Zhang Hui , Li Yu
Published: August 2022

Background

Mantle cell lymphoma (MCL) with Epstein–Barr virus (EBV) infection is rarely reported. The objective of this study was to analyze the prevalence and clinicopathological features of MCL with EBV infection in the largest series thus far.

Methods

After screening 138 cases of MCL, we identified eight cases of MCL with EBV infection.

Results

Most of them (7/8) had non-neoplastic bystander cells with positivity for EBV and no expression of latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2). The cases of MCL with EBER positivity did not have abnormal immune function or other lymphomas. Moreover, their histopathological morphology was indicative of classical MCL. Cases of MCL with EBER positivity exhibited statistically significant differences in lactate dehydrogenase, anemia status, and MCL international prognostic index grouping (P=0.008, P=0.02, P=0.001, and P=0.011, respectively). The differences between the two groups in age, sex ratio, clinical manifestations, and immunohistochemical phenotypes were not statistically significant.

Conclusions

The incidence of MCL with EBV infection was low (5.8%). Clinicopathologically, cases of MCL with EBER positivity were similar to their EBV-negative counterparts. Our findings revealed that most cells infected by EBV in MCL are background cells rather than tumor cells. This is inconsistent with data from previous studies, indicating that tumor cells in MCL may not be prone to EBV infection.
Interpretable clinical visualization model for prediction of prognosis in osteosarcoma: a large cohort data study
Authors: Li Wenle , Jin Genyang , Wu Huitao , Wu Rilige , Xu Chan , Wang Bing , Liu Qiang , Hu Zhaohui , Wang Haosheng , Dong Shengtao , Tang Zhi-Ri , Peng Haiwen , Zhao Wei , Yin Chengliang
Published: August 2022

Background

Currently, the clinical prediction model for patients with osteosarcoma was almost developed from single-center data, lacking external validation. Due to their low reliability and low predictive power, there were few clinical applications. Our study aimed to set up a clinical prediction model with stronger predictive ability, credibility, and clinical application value for osteosarcoma.

Methods

Clinical information related to osteosarcoma patients from 2010 to 2016 was collected in the SEER database and four different Chinese medical centers. Factors were screened using three models (full subset regression, univariate Cox, and LASSO) via minimum AIC and maximum AUC values in the SEER database. The model was selected by the strongest predictive power and visualized by three statistical methods: nomogram, web calculator, and decision tree. The model was further externally validated and evaluated for its clinical utility in data from four medical centers.

Results

Eight predicting factors, namely, age, grade, laterality, stage M, surgery, bone metastases, lung metastases, and tumor size, were selected from the model based on the minimum AIC and maximum AUC value. The internal and external validation results showed that the model possessed good consistency. ROC curves revealed good predictive ability (AUC > 0.8 in both internal and external validation). The DCA results demonstrated that the model had an excellent clinical predicted utility in 3 years and 5 years for North American and Chinese patients.

Conclusions

The clinical prediction model was built and visualized in this study, including a nomogram and a web calculator (https://dr-lee.shinyapps.io/osteosarcoma/), which indicated very good consistency, predictive power, and clinical application value.
Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma
Authors: Zhu Xiao-Ren , Zhu Jia-Qi , Chen Yu-Fei , Liu Yuan-Yuan , Lu Jing-Jing , Sun Jun , Peng Shi-Qing , Chen Min-Bin , Du Yi-Ping
Published: August 2022

Background

Liver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients’ prognosis prediction.

Methods

We collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1.

Results

According to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA.

Conclusion

Our study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.
Bibliometric-Based Evaluation of the Neuromarketing Research Trend: 2010–2021
Authors: Zhu Zeren , Jin Yuanqing , Su Yushun , Jia Kan , Lin Chien-Liang , Liu Xiaoxin
Published: August 2022

Neuromarketing has become a new and important topic in the field of marketing in recent years. Consumer behavior research has received increasing attention. In the past decade, the importance of marketing has also been recognized in many fields such as consumer behavior, advertising, information systems, and e-commerce. Neuromarketing uses neurological methods to determine the driving forces behind consumers’ choices. Various neuroscience tools, such as eye movements, have been adopted to help reveal how consumers react to particular advertisements or objects. This information can be used as the basis for new advertising campaigns and brand promotions. To effectively explore the research trends in this field, we must understand the current situation of neuromarketing. A systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. In this study, journals that focused on neuromarketing in the field of marketing between 2010 and 2021 were analyzed. These journals were core journals rated by the Association of Business Schools with three or more stars. According to the data analysis results, neuromarketing has 15 main journals with relevant papers. Based on the data collected by the Web of Science (WOS), this study mainly collected 119 references and analyzed the most productive countries, universities, authors, journals, and prolific publications in the field of neuromarketing via Citespace. Through the analysis of knowledge maps, this study explored the mapping of co-citation, bibliographic coupling (BC), and co-occurrence (CC). Moreover, the strongest citation bursts were used to study popular research at different time stages and analyze the research trends of neuromarketing research methods and tools. This study provides an overview of the trends and paths in neuromarketing, which can help researchers understand global trends and future research directions.
A comparative analysis of English for academic purposes teachers’ interactive metadiscourse across the British and Chinese contexts
Authors: Wu Xinxin , Yang He
Published: August 2022

This exploratory research compares the interactive metadiscourse use by native English-speaking English for academic purposes (EAP) writing teachers in the United Kingdom and their non-native counterparts in the Chinese contexts. The analysis is based on a self-compiled corpus, including two sub-corpora, which were composed of instructor contributions to classroom discourse: eight sessions of EAP lessons from the Chinese context and eight sessions of EAP lessons from the British context. Adopting an interpersonal model of metadiscourse, the two sub-corpora were compared to examine the similarities and differences in their use of interactive metadiscourse. Findings of the comparative analysis reveal that EAP teachers from both contexts rely heavily on transition markers and frame markers to organize their teaching but differ in particular linguistic realizations. This may indicate the impact of a range of factors such as logical preferences, development order of acquisition, discourse community, and speech community on teachers’ interactive metadiscourse strategies. The article concludes with a few implications for metadiscourse research in spoken academic genres.
The relationship between future self-continuity and intention to use Internet wealth management: The mediating role of tolerance of uncertainty and trait anxiety
Authors: Wang Rongzhao , Lin Xuanxuan , Ye Zetong , Gao Hua , Liu Jianrong
Published: August 2022

This study aimed to analyze the mediating effect of tolerance of uncertainty (TU) and trait anxiety (TA) on future self-continuity (FSC) and intention to use Internet wealth management (IUIWM) systems. A questionnaire survey was distributed online and a total of 388 participants completed questionnaire, The questionnaire included the following scales: Chinese version of the FSC, Intention to Use the Internet Wealth Management, TU, and TA. Pearson correlation was used to investigate the correlation coefficient between variables while the sequential regression method was used to analyze relationship between variables. To analyze the collected data, the SPSS 26.0 was used. A two-step procedure was applied to analyze the mediation effect. Confirmatory factor analysis (CFA) was conducted to test the measurement model. Afterward, the Maximum Likelihood method was used for path analysis, and the Bias-corrected Bootstrap method was used to investigate determine the estimated value and confidence interval of the mediating effect. To analyze the mediation effect, the Mplus 7.0 was used. The results showed that FSC positively predicted individuals’ Internet wealth management systems. Furthermore, TU and TA played complete serial multiple mediating roles between FSC and IUIWM. The role of TA and TU have negative impact on intention to use. This study provides a theoretical basis in personality psychology that Internet financial product suppliers can use to improve the attractiveness of their products. Product managers can subdivide users according to these personality traits to provide customized products.