bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Natural Orifice Specimen Extraction Surgery Really Safe in Radical Surgery for Colorectal Cancer?
Authors: Liu Gang , Shi Lianghui , Wu Zehui
Published: February 2022

Background

The main feature of natural orifice specimen extraction (NOSE) is its avoidance of an auxiliary abdominal incision. The safety of NOSE remains controversial. This study aimed to investigate the early safety of transanal NOSE in the treatment of sigmoid colon and upper rectal cancer from the follow aspects: clinical and pathological characteristics, inflammatory and immune indicators and postoperative complications.

Methods

Data from 125 patients diagnosed with sigmoid colon, and upper rectal cancer by gastrointestinal surgery in the First Affiliated Hospital of Wannan Medical College from January 2017 to June 2020 were analyzed. Patients were assigned to two surgical groups: Conventional laparoscopic-assisted radical resection for CRC (CLA, 75cases) and laparoscopic-assisted radical resection for CRC with NOSE (La-NOSE, 50 cases). The following were compared: clinical and pathological characteristics; intraoperative, bacteriological, and oncological results; postoperative inflammation and immune response indexes. Bacteriological results were obtained by aerobic and anaerobic bacterial culture of peritoneal wash fluid and oncology results by cytological analysis of peritoneal wash liquid exudation. Inflammation indicators included postoperative C-reactive protein (CRP) and procalcitonin (PCT) trend reactions. The immune index was the level of postoperative T lymphocytes (CD3, CD4/CD8). All data were analyzed by using SPSS statistical version 18.0 for windows. Measurement data are presented as the means ± standard deviations, and two-group comparisons were performed using the t-test. Comparisons of count data were performed using the chi-square test. p <0.05 indicates that the difference was statistically significant.

Results

The bacterial culture positive rate was not significant in the La-NOSE group (15/50 vs 19/75) than in the CLA group. The exfoliative cytology (EC) rate of the peritoneal wash fluid was 0 in both groups.The La-NOSE group had a significantly higher postoperative day 2(POD2) CRP and PCT level than the CLA group. The POD2 CD3 and CD4/CD8 levels were higher in the La-NOSE group than in the CLA group. There was no significant difference in the incidence of postoperative complications between the two groups (La-NOSE group vs CLA group: 3/50 vs 6/75) (p>0.05).

Conclusions

Although the incidence of intra-abdominal contamination is high, it does not develop into a severe infectious disease, and does not lead to the implantation of free tumor cells into the abdominal cavity. Therefore, it is safe for the NOSE to treat colorectal cancer.
Assessing the Impact of Green Innovation on Corporate Sustainable Development
Authors: Liao Yu , Qiu Xiaodong , Wu Anni , Sun Qian , Shen Haomin , Li Peiyang
Published: February 2022

Under the background of increasingly prominent environmental problems, exploring the impact of green innovation on the sustainable development ability of enterprises not only can expand the boundary of the research on the factors influencing enterprises’ sustainable development ability and the economic consequences of green innovation but also can provide reference for the decision-making of the listed companies. On the basis of the manual collection of green innovation patent data from China National Intellectual Property Administration, this paper selects the Chinese A-share listed companies from 2010 to 2018 as the research subject and empirically tests the impact of green innovation on the corporate sustainable development ability. The results show that the output of green innovation significantly improves the corporate sustainable development ability. This result is economically significant. Specifically, a one–standard deviation increase (0.8147) of GI translates into a sustainable growth rate of 20.78 percentage points (0.0175*0.8147/0.0686) higher. The relationship between the output of green innovation and corporate sustainable development ability is more significant when the corporate social responsibility performance is worse or scientific research ability is weaker. A series of robustness test results show that the conclusions are reliable. Further test shows that green innovation plays a more significant role in enhancing the corporate sustainable development ability in non–state-owned enterprises. In addition, only invention patents of green innovation can significantly improve the corporate sustainable development ability, whereas non-invention patents cannot affect it. This paper provides a new perspective for the research on the factors affecting the corporate sustainable development ability. Furthermore, the research conclusions of this paper are of reference significance both in theory and practice.
Can Market-Based Environmental Regulation Promote Green Technology Innovation? Evidence from China
Authors: Qu Fang , Xu Lei , Chen Yufeng
Published: February 2022

To alleviate climate change and environmental issues, China has implemented many environmental regulation policies. This paper takes the SO2 and carbon emission trading pilots (SETP, CETP) in China as the quasi-experiment and, under the difference-in-difference framework, studies whether the market-based environmental regulation (MER) policy promotes green technology innovation. The investigation is conducted employing patent data with the “IPC Green Inventory” on the panel data of China’s 278 prefectural-level cities over the period 2003–2017. We found that 1) as for a single policy, SETP successfully promoted green technology innovation, but failed in CETP, which shows that not all MER policies can play a positive effect on green technology innovation. Meanwhile, SETP and CETP did not change the direction of technology innovation and had no impact on total technology innovation. 2) For the combination policy, SETP and CETP failed to jointly promote green technology innovation, and with the current MER policy in China, it is difficult to realize the policy combination effect. This result implies that repeated implementation of similar environmental policies failed to stimulate innovation. 3) Heterogeneity analysis shows that the promotion effect of SETP on green technology innovation, mainly in the eastern region, and the promotion effect on invention patents is more prominent than utility model patents, which shows that green technology has improved not only in quantity but also in quality. These findings provide empirical evidence and policy implication for the efficient implementation of environmental regulation.
Occurrence and Livestock Depredation Patterns by Wolves in Highly Cultivated Landscapes
Authors: Mayer Martin , Olsen Kent , Schulz Björn , Matzen Jens , Nowak Carsten , Thomsen Philip Francis , Hansen Michael Møller , Vedel-Smith Christina , Sunde Peter
Published: February 2022

Attacks by large predators on livestock are an important driver of conflicts. Consequently, knowledge about where predators occur, where livestock depredation takes place and what factors influence it will aid the mitigation of stakeholder conflicts. Following legal protection, wolves (Canis lupus) in Central Europe are recently spreading to areas dominated by agriculture, bringing them in closer contact with livestock. Here, we analyzed habitat selection and livestock depredation rates of 43 wolves identified by genotyping on the Jutland peninsula, consisting of mainland Denmark and the northernmost German federal state Schleswig-Holstein. Occupancy by resident wolves correlated positively with forest and other non-forested semi-natural land cover (habitat for natural ungulate prey), whereas occupancy by non-resident wolves correlated with increasing forest cover and sheep density. The latter effect likely reflected increased sampling probability of highly mobile dispersers killing livestock. We recorded 565 livestock depredation events (85 in Denmark and 480 in Schleswig-Holstein), of which 42% (55 in DK and 185 in SH) could be assigned to 27 individual wolves based on DNA evidence. Livestock (mostly sheep) were killed by wolves in 16% of the study area. Our results indicate that wolves mostly killed livestock as a context-dependent response, i.e., being dispersers in agricultural areas with low availability of wild ungulate prey and high livestock densities, and not because of behavioral preferences for sheep. Moreover, the livestock depredation was lower in areas with livestock protection measures (implemented in areas with established pairs/packs). We conclude that while wolf attacks on livestock in established wolf territories generally can be reduced through improvement of fences, livestock depredation by non-resident wolves in agricultural areas constitutes a bigger challenge. Albeit technically possible, the economic costs of implementing predator-proof fences and other preventive measures in such pastoral areas infrequently visited by wolves will be considerable. Experiences so far further indicate that lethal removal of identified “problem wolves” may be inefficient in practice.
DNTTIP1 is a Prognostic Biomarker Correlated With Immune Infiltrates in Hepatocellular Carcinoma: A Study Based on The Cancer Genome Atlas Data
Authors: Zhu Changyu , Tong Rongsheng , Jiang Xiaolei , Xiao Hua , Guan Jianmei , Shu Jianchen
Published: February 2022

Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) is involved in the deacetylation of p53 in regulating cell cycle and is associated with cancers at the molecular level. In this study, we evaluated the prognostic value in hepatocellular carcinoma (HCC) based on data from The Cancer Genome Atlas (TCGA) database. Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between DNTTIP1 expression and clinicopathological features. Cox regression and the Kaplan–Meier method were adopted to evaluate prognosis-related factors. Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to DNTTIP1. The correlations between DNTTIP1 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis (ssGSEA). DNTTIP1 was found to be upregulated with amplification in tumor tissues in multiple HCC cohorts. High DNTTIP1 expression was associated with poorer overall survival (OS) and disease-free survival (DFS). GSEA suggested that DNTTIP1 regulates the cell cycle mitotic, G1/S, and G2/M phases and Fc fragment of IgE receptor I (FCERI)–mediated NF-κB and MAPK pathway and Fc fragment of IgG receptor (FCGR) activation pathways. Notably, ssGSEA indicated that DNTTIP1 expression was positively correlated with infiltrating levels of Th2 cells, Tfh, NK CD56 bright cells, aDCs, T helper cells, Th1 cells, and macrophages. These findings suggest that DNTTIP1 is correlated with prognosis and immune infiltration in HCC, which lays a foundation for further study of the immune-regulatory role of DNTTIP1 in HCC.
The Landscape of Featured Metabolism-Related Genes and Imbalanced Immune Cell Subsets in Sepsis
Authors: She Han , Tan Lei , Zhou Yuanqun , Zhu Yu , Ma Chunhua , Wu Yue , Du Yuanlin , Liu Liangming , Hu Yi , Mao Qingxiang , Li Tao
Published: February 2022

Sepsis is a heterogeneous disease state triggered by an uncontrolled inflammatory host response with high mortality and morbidity in severely ill patients. Unfortunately, the treatment effectiveness varies among sepsis patients and the underlying mechanisms have yet to be elucidated. The present aim is to explore featured metabolism-related genes that may become the biomarkers in patients with sepsis. In this study, differentially expressed genes (DEGs) between sepsis and non-sepsis in whole blood samples were identified using two previously published datasets (GSE95233 and GSE54514). A total of 66 common DEGs were determined, namely, 52 upregulated and 14 downregulated DEGs. The Gene Set Enrichment Analysis (GSEA) results indicated that these DEGs participated in several metabolic processes including carbohydrate derivative, lipid, organic acid synthesis oxidation reduction, and small-molecule biosynthesis in patients with sepsis. Subsequently, a total of 8 hub genes were screened in the module with the highest score from the Cytoscape plugin cytoHubba. Further study showed that these hub DEGs may be robust markers for sepsis with high area under receiver operating characteristic curve (AUROC). The diagnostic values of these hub genes were further validated in myocardial tissues of septic rats and normal controls by untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Immune cell infiltration analysis revealed that different infiltration patterns were mainly characterized by B cells, T cells, NK cells, monocytes, macrophages, dendritics, eosinophils, and neutrophils between sepsis patients and normal controls. This study indicates that metabolic hub genes may be hopeful biomarkers for prognosis prediction and precise treatment in sepsis patients.
Are UK Policies and Practices for Regulated Donor Insemination Forcing Women to Find Unregulated Sperm Donors Online? A Perspective on the Available Evidence
Authors: Taylor Francesca , Turner-Moore Rhys , Pacey Allan , Jones Georgina Louise
Published: February 2022

In recent years, there has been an increase in women obtaining donor sperm via unregulated websites and social media. In this article, we bring together the disparate evidence in this emerging field to consider whether restrictive UK policies and practices for regulated clinical donor insemination (DI) are a potential explanation for the growing use of the currently unregulated, online route to donor insemination. To this end, we examine the nature of the National Institute for Health and Care Excellence (NICE) guidelines, recent data provided by the Human Fertilisation and Embryology Authority (HFEA), and prior research on who uses online sperm donation and their reasons for doing so. In addition, we highlight why this issue is important by outlining some of the benefits and drawbacks of the unregulated route. We argue that, whilst there are many factors driving the unregulated route to DI, restrictive UK policies and practices for regulated DI might be one of these. We conclude that turning our attention to structural barriers, such as regulated DI policies and practices, is necessary to produce more definitive evidence of this potential issue, and that adopting a Reproductive Justice framework could lead to more equitable provision of regulated DI services.
High-Dimensional Analysis Reveals Distinct Endotypes in Patients With Idiopathic Inflammatory Myopathies
Authors: Wilfong Erin M. , Bartkowiak Todd , Vowell Katherine N. , Westlake Camille S. , Irish Jonathan M. , Kendall Peggy L. , Crofford Leslie J. , Bonami Rachel H.
Published: February 2022

The idiopathic inflammatory myopathies (IIM) are a rare clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. While myositis specific autoantibodies are well described, we postulate that broader immune endotypes exist in IIM spanning B cell, T cell, and monocyte compartments. This study aims to identify immune endotypes through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients compared to healthy controls. We collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis and characterized the B, T, and myeloid cell subsets using mass cytometry by time of flight (CyTOF). Data were analyzed using a combination of the dimensionality reduction algorithm t-distributed stochastic neighbor embedding (t-SNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM); supervised biaxial gating validated populations identified by these methods to be differentially abundant between groups. Using these approaches, we identified shared immunologic features across all IIM patients, despite different clinical features, as well as two distinct immune endotypes. All IIM patients had decreased surface expression of RP105/CD180 on B cells and a reduction in circulating CD3+CXCR3+ subsets relative to healthy controls. One IIM endotype featured CXCR4 upregulation across all cellular compartments. The second endotype was hallmarked by an increased frequency of CD19+CD21loCD11c+ and CD3+CD4+PD1+ subsets. The experimental and analytical methods we describe here are broadly applicable to studying other immune-mediated diseases (e.g., autoimmunity, immunodeficiency) or protective immune responses (e.g., infection, vaccination).
CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma
Authors: Jiang Yuan , Ji Qiankun , Long Xiaoyan , Wang Peng , Tu Zewei , Zhang Xian , Zhu Xingen , Huang Kai , Li Jingying
Published: February 2022

Background

Cardiotrophin-like cytokine factor 1 (CLCF1) has been described as an oncogene and a potential therapeutic target in a variety of cancers, but its role in glioma remains unknown.

Methods

Based on The Cancer Genome Atlas (TCGA), we conducted a bioinformatics analysis to investigate the clinical significance and biological functions of CLCF1 in glioma at the transcriptional level and predicted the response to immunotherapy of glioma patients with different CLCF1 expression levels. All the results were further verified in Chinese Glioma Genome Altas(CGGA) Data processing and figure generating were performed with R language.

Results

Elevated CLCF1 expression was common in cancers and usually predicted poor prognosis, which was also consistent with gliomas. In Univariate Cox Regression analysis and Kaplan-Meier survival analysis, tumor patients with higher CLCF1 expression tended to experience a worse prognosis. In the multivariate Cox proportional hazard model, the expression of CLCF1 was an independent prognostic factor in gliomas. The biological function analysis of CLCF1 in glioma showed that CLCF1 was closely associated with immune signatures, including immune-related pathways, immune cell infiltration, and immune checkpoints. Moreover, glioma patients with low CLCF1 expression showed a greater tendency to respond to anti-PD1/PD-L1 immunotherapy, indicating CLCF1 also had potential clinical significance in guiding immunotherapy. And CLCF1 as a member of the IL6 family had a better predictive value for prognosis and immunotherapy response in glioma than that of IL6 and other IL6 family members.

Conclusion

CLCF1 expression is an independent prognosticator and a promising therapeutic target correlated with immunotherapy in glioma.
Chronic Inflammation Might Protect Hemodialysis Patients From Severe COVID-19
Authors: Prietl Barbara , Odler Balazs , Kirsch Alexander H. , Artinger Katharina , Eigner Manfred , Schmaldienst Sabine , Pfeifer Verena , Stanzer Stefanie , Eberl Anita , Raml Reingard , Pieber Thomas , Rosenkranz Alexander R. , Brodmann Marianne , Eller Philipp , Eller Kathrin
Published: February 2022

Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19.

Methods

Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed COVID-19 and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild, moderate or severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping was performed.

Results

Th1 and Th17 plasma cytokine levels were highly increased in HD patients without COVID-19 and were not significantly regulated during COVID-19. In non-HD COVID-19 patients these cytokines increased significantly with disease severity. While all patients with moderate or severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+, CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in moderate/severe COVID-19 HD patients, which was not observed in non-HD patients with moderate or severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients.

Conclusions

HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.
High Immunogenicity of a T-Cell Epitope-Rich Recombinant Protein Rv1566c-444 From Mycobacterium tuberculosis in Immunized BALB/c Mice, Despite Its Low Diagnostic Sensitivity
Authors: Luan Xiuli , Fan Xueting , Wang Ruihuan , Deng Yunli , Chen Zixin , Li Na , Yan Yuhan , Li Xiaoyan , Liu Haican , Li Guilian , Wan Kanglin
Published: February 2022

The discovery of immunodominant antigens is of great significance for the development of new especially sensitive diagnostic reagents and effective vaccines in controlling tuberculosis (TB). In the present study, we targeted the T-Cell epitope-rich fragment (nucleotide position 109-552) of Rv1566c from Mycobacterium tuberculosis (MTB) and got a recombinant protein Rv1566c-444 and the full-length protein Rv1566c with Escherichia coli expression system, then compared their performances for TB diagnosis and immunogenicity in a mouse model. The results showed that Rv1566c-444 had similar sensitivity with Rv1566c (44.44% Vs 30.56%) but lower sensitivity than ESAT-6&CFP-10&Rv3615c (44.4% Vs. 94.4%) contained in a commercial kit for distinguishing TB patients from healthy donors. In immunized BALB/c mice, Rv1566c-444 elicited stronger T-helper 1 (Th1) cellular immune response over Rv1566c with higher levels of Th1 cytokine IFN-γ and IFN-γ/IL-4 expression ratio by ELISA; more importantly, with a higher proliferation of CD4+ T cells and a higher proportion of CD4+ TNF-α+ T cells with flow cytometry. Rv1566c-444 also induced a higher level of IL-6 by ELISA and a higher proportion of Rv1566c-444-specific CD8+ T cells and a lower proportion of CD8+ IL-4+ T cells by flow cytometry compared with the Rv1566c group. Moreover, the Rv1566c-444 group showed a high IgG secretion level and the same type of CD4+ Th cell immune response (both IgG1/IgG2a >1) as its parental protein group. Our results showed the potential of the recombinant protein Rv1566c-444 enriched with T-Cell epitopes from Rv1566c as a host T cell response measuring biomarker for TB diagnosis and support further evaluation of Rv1566c-444 as vaccine antigen against MTB challenge in animal models in the form of protein mixture or fusion protein.
Effects of Epiphytes on the Seagrass Phyllosphere
Authors: Brodersen Kasper Elgetti , Kühl Michael
Published: February 2022

The seagrass phyllosphere consists of a dynamic mosaic of physico-chemical microgradients that modulate light harvesting, gas and nutrient exchange between the photosynthetic leaves and the surrounding water-column. The phyllosphere is thus of vital importance for seagrass growth and fitness. However, unfavorable environmental conditions such as water-column hypoxia, increasing temperature and high nutrient inputs that are predicted to increase in frequency and severity in the Anthropocene, can render the leaf microenvironment into a hostile microhabitat that is challenging or even harmful for the plants—especially if leaves are covered by epiphytic biofilms. Here we summarize effects of epiphytic biofilms on seagrass leaves and discuss how they change and affect the biogeochemical processes and chemical conditions in the seagrass phyllosphere. During night-time, water-column hypoxia can lead to anoxic conditions at the leaf/epiphyte interface, reducing diffusive O2supply and thus O2availability for plant respiration and transport to below-ground tissues. Furthermore, anoxia in epiphytic biofilms can also enable anaerobic microbial processes that can lead to harmful nitric oxide productionviadenitrification. Such microenvironmental stress conditions at night-time are exacerbated by increasing temperatures. In the light, the leaf epiphytic biofilm community often results in lower leaf photosynthetic activity and efficiency due to epiphyte-induced shading and a combination of O2build-up and CO2reduction in the phyllosphere owing to thicker total diffusional pathways, phyllosphere basification and epiphytic carbon fixation. Furthermore, absorbed light energy in the epiphytic biofilm can also drive an increase in the leaf surface temperature relative to the surrounding seawater potentially aggravating heating events in the surrounding seawater. In combination, all these above-mentioned diurnal effects of epiphytes result in higher compensation photon irradiance of epiphyte-covered leaves and thus higher light requirements of seagrasses.
Matching the Color Difference Between Asphalt Mixture and Cement Grouting Paste Used in Semi-flexible Pavement
Authors: Haibin Deng , Shungui Wang , Yingchen Liu , Yinfei Du , Tangzhong Wei
Published: February 2022

In order to match the color difference between black asphalt mixture and light-colored cement grouting paste in semiflexible pavement, carbon black (CB) with four mass ratios (i.e., 2, 4, 6, and 8%) was incorporated into a rapid-hardening cement grouting paste. The fluidity, color difference, spectrum reflectance, thermal conductivity, and flexural and compressive strength of the aforementioned cement pastes were experimentally investigated. The results show that the mass ratios of the component in cement paste could ensure the good fluidity of cement grouting paste. Three parameters such as thermal conductivity, flexural strength, and compressive strength all reduced, compared with control paste. However, the compressive strength of the 8% CB paste was still much higher than that of the asphalt mixture. According to the color difference results, CB significantly improved the black color of cement paste, of which the black color of the asphalt mixture was between that of 6 and 8% CB cement paste. Besides, the spectrum reflectance of all the pastes reduced, especially the average reflectance of 2% CB cement paste was 51.7% lower than that of control paste. The findings in this study are expected to help design more advanced cement grouting materials to improve the optical and mechanical performances of semiflexible asphalt pavement.
Association Between Atopic Dermatitis, Asthma, and Serum Lipids: A UK Biobank Based Observational Study and Mendelian Randomization Analysis
Authors: Tang Zhenwei , Shen Minxue , Xiao Yi , Liu Hong , Chen Xiang
Published: February 2022

Background

Both atopic diseases and dysregulation of serum lipids (SLs) add to significant health burden, but evidences about their association are inconsistent.

Objective

This work is to evaluate the association between asthma/atopic dermatitis (AD) and SLs and investigate the potential causal relationship.

Methods

A large-scale cross-sectional study based on the UK Biobank (UKB) and then examined the casual relationships between SLs with asthma/AD based on a Mendelian randomization (MR) analysis.

Results

A total of 502,505 participants were included in analysis. After full adjustment, AD was associated with lower TG (β = −0.006; 95%CI, −0.010 to −0.002; P = 0.006), lower LDL (β = −0.004; 95%CI, −0.006 to −0.002, P < 0.001), and lower TC (β = −0.004; 95%CI, −0.005 to −0.002; P < 0.001) but insignificantly correlated to HDL (P = 0.794). Asthma was also inversely correlated to TG (β = −0.005; 95%CI, = −0.007 to −0.003; < 0.001), LDL (β = −0.003; 95%CI, −0.004 to −0.002; P < 0.001), and TC (β = −0.002; 95%CI, −0.003 to −0.002; P < 0.001), but was positively correlated to HDL (β = 0.004; 95%CI, 0.003 to 0.005; P < 0.001), respectively. In subsequent MR analysis, both allergic diseases and asthma showed a protective effect on TC. Allergic diseases, asthma, and AD all showed a negative effect on LDL.

Conclusion

Collectively, we identify a protective causal effect of allergic diseases on serum lipids, as well as a potentially positive association of HDL with asthma. Owing to the largest sample size and the application of IVs in causal inference, this study will provide a robust evidence for the management of asthma and AD and the prevention of dyslipidemia.
The Efficacy and Safety of Early Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials
Authors: Xiao Chuan , Xiao Jingjing , Cheng Yumei , Li Qing , Li Wei , He Tianhui , Li Shuwen , Gao Daixiu , Shen Feng
Published: February 2022

The efficacy and safety of early renal replacement therapy (eRRT) for critically ill patients with acute kidney injury (AKI) remain controversial. Therefore, the purpose of our study was to perform an up-to-date meta-analysis with the trial sequential analysis (TSA) of randomized controlled trials (RCTs) to evaluate the therapeutic effect of eRRT on patients in an intensive care unit (ICU). We extensively searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, Gray Literature Report, and Bielefeld Academic Search Engine (BASE), and conducted an updated search on December 27, 2021. The included studies were RCTs, which compared the efficacy and safety of eRRT and delayed renal replacement therapy (dRRT) on critically ill patients with AKI. We adopted TSA and sensitivity analysis to strengthen the robustness of the results. About 12 RCTs with a total of 5,423 participants were included. Patients receiving eRRT and dRRT had the similar rate of all-cause mortality at day 28 (38.7% vs. 38.9%) [risk ratio (RR), 1.00; 95%CI, 0.93–1.07, p = 0.93, I2 = 0%, p = 0.93]. A sensitivity and subgroup analysis produced similar results for the primary outcome. TSA showed that the required information size was 5,034, and the cumulative Z-curve crossed trial sequential monitoring boundaries for futility. Patients receiving eRRT had a higher rate of renal replacement therapy (RRT) (RR, 1.50, 95% CI: 1.28–1.76, p < 0.00001, I2 = 96%), and experienced more adverse events comparing to those receiving dRRT (RR: 1.41, 95% CI: 1.22–1.63, p < 0.0001, heterogeneity not applied). The most remarkable and important experimental finding is that, to our knowledge, the current meta-analysis included the largest sample size from the RCTs, which were published in the past 10 years to date, show that eRRT had no significant survival benefit for ill patients with AKI compared with dRRT and TSA indicating that no more studies were needed to confirm it.

Trial Registration

INPLASY, INPLASY2020120030. Registered 04 December 2020.
Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages
Authors: Mostefai Fatima , Gamache Isabel , N'Guessan Arnaud , Pelletier Justin , Huang Jessie , Murall Carmen Lia , Pesaranghader Ahmad , Gaonac'h-Lovejoy Vanda , Hamelin David J. , Poujol Raphaël , Grenier Jean-Christophe , Smith Martin , Caron Etienne , Craig Morgan , Wolf Guy , Krishnaswamy Smita , Shapiro B. Jesse , Hussin Julie G.
Published: February 2022

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.
Comparison of Gut Viral Communities in Atopic Dermatitis and Healthy Children
Authors: Lu Xiang , Wang Hao , Zhang Jingqi , Jin Kexin , Ma Ling , Wang Yan , Yang Shixing , Wang Xiaochun , Shen Quan , Zhou Tianji , Xu Hui , Zhang Wen
Published: February 2022

The immune development and regulation of living individuals are affected by the gut microbiota. The imbalance of gut microbiota is considered to be a key factor that easily induces immune dysregulation and the development of atopic diseases. Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects nearly 20% of children. To date, metagenomics research on AD has mainly focused on the skin and gut microbiome. However, here we assessed the composition of the virome in the gut of AD patients and healthy controls for the first time. This study has obtained possible dominant viruses at different viral classification levels. In terms of diversity, the alpha diversity of the patients group was significantly lower than that of the healthy controls group, and the beta diversity of the two groups was significantly different from phylum to family level. These findings provide a new perspective for us to better understand the effect of the gut microecological environment on AD.
Effect of Pulmonary Rehabilitation for Patients With Post-COVID-19: A Systematic Review and Meta-Analysis
Authors: Chen Huan , Shi Hangyu , Liu Xitong , Sun Tianheng , Wu Jiani , Liu Zhishun
Published: February 2022

Background

Evidence increasingly suggested that impaired respiratory function remained in about 40% of patients with coronavirus disease 2019 (COVID-19) after discharge, jeopardizing their activities of daily living and quality of life (QoL) in a long term. Pulmonary rehabilitation (PR) can improve exercise capacity and QoL in individuals with chronic lung disease; however, evidence on the effect of PR for patients with post-COIVD-19 was scarce. This study aimed to conduct a systematic review and meta-analysis to evaluate the effect of PR on lung impairment for patients with post-COVID-19.

Methods

Five databases were searched for all the published trials of PR for patients with post-COVID-19 from 2019 to October 2021. Data were extracted using a standardized form. The risks of bias of included studies were assessed using the Cochrane risk of the bias assessment tool. Data were synthesized where possible; otherwise, qualitative analysis was done.

Results

Among 6,000 retrieved studies, 3 studies with 233 patients after COVID-19 were included. The pooled estimate of PR effect on 6-min walk test (6-MWT) (50.41, 95% CI 34.34 to 66.48; p < 0.0001) was in favor of the experiment group with clinical importance. It is found that PR could improve the symptom of dyspnea and QoL; however, its effect on pulmonary function test was inconsistent across studies. The risk of bias of included studies varied, with major concerns on the risk of blinding of participants and interventions performers.

Conclusion

The review showed that PR could improve exercise capacity measured by 6-MWT among patients with mild-to-moderate lung impairment after COVID-19. The interpretation of effects on lung function, dyspnea, and QoL should be cautious due to inadequate and conflicting data reported across studies.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289562, identifier: CRD42021289562.
Comparative Genome Analysis Reveals Cis-Regulatory Elements on Gene-Sized Chromosomes of Ciliated Protists
Authors: Zheng Weibo , Dou Huan , Li Chao , Al-Farraj Saleh A. , Byerly Adam , Stover Naomi A. , Song Weibo , Chen Xiao , Li Lifang
Published: February 2022

Gene-sized chromosomes are a distinct feature of the macronuclear genome in ciliated protists known as spirotrichs. These nanochromosomes are often only several kilobase pairs long and contain a coding region for a single gene. However, the ways in which transcription is regulated on nanochromosomes is still largely unknown. Here, we generated macronuclear genome assemblies for two species of Pseudokeronopsis ciliates to better understand transcription regulation on gene-sized chromosomes. We searched within the short subtelomeric regions for potential cis-regulatory elements and identified distinct AT-rich sequences conserved in both species, at both the 5’ and 3’ end of each gene. We further acquired transcriptomic data for these species, which showed the 5’ cis-regulatory element is associated with active gene expression. Gene family evolution analysis suggests nanochromosomes in spirotrichs may originated approximately 900 million years ago. Together our comparative genomic analyses reveal novel insights into the biological roles of cis-regulatory elements on gene-sized chromosomes.
Virome Status of Preclonal Candidates of Grapevine Varieties (Vitis vinifera L.) From the Slovenian Wine-Growing Region Primorska as Determined by High-Throughput Sequencing
Authors: Miljanić Vanja , Jakše Jernej , Kunej Urban , Rusjan Denis , Škvarč Andreja , Štajner Nataša
Published: February 2022

Diseases caused by viruses and virus-like organisms are one of the major problems in viticulture and grapevine marketing worldwide. Therefore, rapid and accurate diagnosis and identification is crucial. In this study, we used HTS of virus- and viroid-derived small RNAs to determine the virome status of Slovenian preclonal candidates of autochthonous and local grapevine varieties (Vitis vinifera L.). The method applied to the studied vines revealed the presence of nine viruses and two viroids. All viral entities were validated and more than 160 Sanger sequences were generated and deposited in NCBI. In addition, a complete description into the co-infections in each plant studied was obtained. No vine was found to be virus- and viroid-free, and no vine was found to be infected with only one virus or viroid, while the highest number of viral entities in a plant was eight.
Clinical Prognostic Value of the PLOD Gene Family in Lung Adenocarcinoma
Authors: Meng Yiming , Sun Jing , Zhang Guirong , Yu Tao , Piao Haozhe
Published: February 2022

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan–Meier method. A protein–protein interaction network was constructed using STRING software. The “ClusterProfiler” package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan–Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.
Comprehensive Characterization of Ageing-Relevant Subtypes Associated With Different Tumorigenesis and Tumor Microenvironment in Prostate Cancer
Authors: Huang Liang , Xu Zhenzhou , Xie Yu , Jiang Shusuan , Han Weiqing , Tang Zhengyan , Zhu Quan
Published: February 2022

Objective: Accumulated evidence demonstrates that ageing is a robust risk factor of prostate cancer prognosis. Herein, we conducted a systematic analysis about ageing-relevant molecules and relevant tumor microenvironment features in prostate cancer.

Methods: Transcriptome data, clinical information, and mutational data of prostate cancer patients were retrospectively collected from the Cancer Genome Atlas cohort. In accordance with the expression of specific ageing-relevant genes, prostate cancer patients were clustered with consensus clustering analyses. WGCNA was adopted for determination of subtype-associated co-expression modules and genes. Thereafter, characteristic genes were further screened with random forest algorithm and a prognostic model was conducted with multivariate cox regression analyses. Tumor microenvironment-infiltrating immune cells were estimated with ssGSEA and ESTIMATE. Activities of the cancer immunity cycle and expressions of HLA and immune checkpoint molecules were then quantified across prostate cancer cases. A serious experiment was conducted to investigate the roles of EIF2S2 in prostate tumorigenesis.

Results: This study characterized three ageing-relevant subtypes (C1, C2, and C3) with diverse clinical prognosis. Subtype C1 presented the features of low mutational frequency and immune activation; C2 was characterized by stromal and immune activation; and C3 showed immune suppression. An ageing-derived gene signature was conducted, which independently and robustly predicted patients’ prognosis. Additionally, this signature was in relation to immune inactivation. Among the genes in the signature, EIF2S2 triggered proliferation, invasion, and migration of LNCaP and PC-3 cells.

Conclusion: Collectively, ageing-relevant molecular subtypes and gene signature might be of great significance to determine clinical outcomes and tumor microenvironment features and immunotherapeutic responses in prostate cancer.
Insight Into the Effects of Clinical Repetitive Transcranial Magnetic Stimulation on the Brain From Positron Emission Tomography and Magnetic Resonance Imaging Studies: A Narrative Review
Authors: Aceves-Serrano Lucero , Neva Jason L. , Doudet Doris J.
Published: February 2022

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a therapeutic tool to alleviate symptoms for neurological and psychiatric diseases such as chronic pain, stroke, Parkinson’s disease, major depressive disorder, and others. Although the therapeutic potential of rTMS has been widely explored, the neurological basis of its effects is still not fully understood. Fortunately, the continuous development of imaging techniques has advanced our understanding of rTMS neurobiological underpinnings on the healthy and diseased brain. The objective of the current work is to summarize relevant findings from positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques evaluating rTMS effects. We included studies that investigated the modulation of neurotransmission (evaluated with PET and magnetic resonance spectroscopy), brain activity (evaluated with PET), resting-state connectivity (evaluated with resting-state functional MRI), and microstructure (diffusion tensor imaging). Overall, results from imaging studies suggest that the effects of rTMS are complex and involve multiple neurotransmission systems, regions, and networks. The effects of stimulation seem to not only be dependent in the frequency used, but also in the participants characteristics such as disease progression. In patient populations, pre-stimulation evaluation was reported to predict responsiveness to stimulation, while post-stimulation neuroimaging measurements showed to be correlated with symptomatic improvement. These studies demonstrate the complexity of rTMS effects and highlight the relevance of imaging techniques.
Combining Dynamic Network Analysis and Cerebral Carryover Effect to Evaluate the Impacts of Reading Social Media Posts and Science Fiction in the Natural State on the Human Brain
Authors: Hu Bo , Cui Yu-Ling , Yu Ying , Li Yu-Ting , Yan Lin-Feng , Sun Jing-Ting , Sun Qian , Zhang Jing , Wang Wen , Cui Guang-Bin
Published: February 2022

Social media has been associated with decreased attention, memory, and learning abilities; however, the underlying mechanisms remain unclear. Dynamic function network connectivity (dFNC) analysis is suitable for uncovering dynamical brain activity. Besides, the effects of a cognitive task may persist for a while on the brain, even after the termination of the task, also known as the carryover effect. Consequently, we combined the dFNC analysis and cerebral carryover effects to study the brain dynamics of reading social media posts in the natural state and comparatively investigated the brain dynamics of reading science fiction on the smartphone. We performed functional MRI (fMRI) scans of all subjects at baseline and then assigned them a social media post or science fiction reading task. Immediately after, another fMRI scanning was performed for these subjects. We found that the change between dFNC states, the number of dFNC states, and the total distances increased after reading science fiction. Furthermore, the global, local, and nodal efficiencies of the deep-thinking state tended to increase after reading science fiction. On reading social media posts, the functional connectivity (FC) between the default mode network (DMN) and bilateral frontoparietal network (FPN) decreased, while the FC between DMN and visual network (VN) increased. Given the current evidence, we concluded that reading science fiction could substantially increase brain activity and network efficiency, while social media was related to abnormal FCs between DMN, VN, and FPN.