bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Validation of Constructing the Prognostic Model With Four DNA Methylation-Driven Genes in Pancreatic Cancer
Authors: Chen Guangyu , Long Junyu , Zhu Ruizhe , Yang Gang , Qiu Jiangdong , Zhao Fangyu , Liu Yuezhe , Tao Jinxin , Zhang Taiping , Zhao Yupei
Published: January 2022

Background: Pancreatic cancer (PC) is a highly aggressive gastrointestinal tumor and has a poor prognosis. Evaluating the prognosis validly is urgent for PC patients. In this study, we utilized the RNA-sequencing (RNA-seq) profiles and DNA methylation expression data comprehensively to develop and validate a prognostic signature in patients with PC.

Methods: The integrated analysis of RNA-seq, DNA methylation expression profiles, and relevant clinical information was performed to select four DNA methylation-driven genes. Then, a prognostic signature was established by the univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses in The Cancer Genome Atlas (TCGA) dataset. GSE62452 cohort was utilized for external validation. Finally, a nomogram model was set up and evaluated by calibration curves.

Results: Nine DNA methylation-driven genes that were related to overall survival (OS) were identified. After multivariate Cox and LASSO regression analyses, four of these genes (RIC3, MBOAT2, SEZ6L, and OAS2) were selected to establish the predictive signature. The PC patients were stratified into two groups according to the median risk score, of which the low-risk group displayed a prominently favorable OS compared with the high-risk group, whether in the training (p < 0.001) or validation (p < 0.01) cohort. Then, the univariate and multivariate Cox regression analyses showed that age, grade, risk score, and the number of positive lymph nodes were significantly associated with OS in PC patients. Therefore, we used these clinical variables to construct a nomogram; and its performance in predicting the 1-, 2-, and 3-year OS of patients with PC was assessed via calibration curves.

Conclusion: A prognostic risk score signature was built with the four alternative DNA methylation-driven genes. Furthermore, in combination with the risk score, age, grade, and the number of positive lymph nodes, a nomogram was established for conveniently predicting the individualized prognosis of PC patients.
Characterization of m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration in Ovarian Cancer
Authors: Luo Yihong , Sun Xiang , Xiong Jian
Published: January 2022

Introduction: Studies have demonstrated the epigenetic regulation of immune responses in various cancers. However, little is known about the RNA N6-methyladenosine (m6A) modification patterns of the microenvironment (TME) cell infiltration in ovarian cancer (OC).

Methods: We evaluated the correlation between m6A modification patterns and TME cell infiltration based on 459 OC samples from the Cancer Genome Atlas and Gene-Expression Omnibus database. We constructed an m6Ascore system to quantify m6A modification patterns using principal component analysis.

Results: Based on unsupervised clustering, three m6A modification patterns were identified. Gene set variation analysis showed that the antigen presentation signal pathway, the NOTCH signaling pathway, and the metabolism-related pathway differed significantly across m6A modificaiton patterns. The m6Ascore is closely correlated with TME cell infiltration. OC patients with lower m6Ascores had worse outcomes. There was better risk stratification with combined m6Ascore and tumor mutation burden. The responses to immune checkpoint inhibitor treatment significantly differed between high and low m6Ascore groups.

Conclusion: M6A modification plays an essential role in TME cell infiltration in OC. Evaluating the m6A modification patterns in OC patients could enhance our understanding of TME infiltration characterization and guide immunotherapy strategies.
Semi-Supervised Learning–Based Petrophysical Facies Division and “Sweet Spot” Identification of Low-Permeability Sandstone Reservoir
Authors: Fan Hongjun , Zhao Xiaoqing , Liang Xu , Miao Quansheng , Jin Yongnian , Wang Xiangyu
Published: January 2022

The identification of the “sweet spot” of low-permeability sandstone reservoirs is a basic research topic in the exploration and development of oil and gas fields. Lithology identification, reservoir classification based on the pore structure and physical properties, and petrophysical facies classification are common methods for low-permeability reservoir classification, but their classification effect needs to be improved. The low-permeability reservoir is characterized by low rock physical properties, small porosity and permeability distribution range, and strong heterogeneity between layers. The seepage capacity and productivity of the reservoir vary considerably. Moreover, the logging response characteristics and resistivity value are similar for low-permeability reservoirs. In addition to physical properties and oil bearing, they are also affected by factors such as complex lithology, pore structure, and other factors, making it difficult for division of reservoir petrophysical facies and “sweet spot” identification. In this study, the logging values between low-porosity and -permeability reservoirs in the Paleozoic Es3 reservoir in the M field of the Bohai Sea, and between natural gamma rays and triple porosity reservoirs are similar. Resistivity is strongly influenced by physical properties, oil content, pore structure, and clay content, and the productivity difference is obvious. In order to improve the identification accuracy of “sweet spot,” a semi-supervised learning model for petrophysical facies division is proposed. The influence of lithology and physical properties on resistivity was removed by using an artificial neural network to predict resistivity R0 saturated with pure water. Based on the logging data, the automatic clustering MRGC algorithm was used to optimize the sensitive parameters and divide the logging facies to establish the unsupervised clustering model. Then using the divided results of mercury injection data, core cast thin layers, and logging faces, the characteristics of diagenetic types, pore structure, and logging response were integrated to identify rock petrophysical facies and establish a supervised identification model. A semi-supervised learning model based on the combination of “unsupervised supervised” was extended to the whole region training prediction for “sweet spot” identification, and the prediction results of the model were in good agreement with the actual results.
Gender Differences in Social Comparison Processes and Self-Concept Among Students
Authors: Valls Marjorie
Published: January 2022

Forced social comparison (i.e., comparing oneself to another “predefined” student) has often been studied in school settings. However, to our knowledge, studies that explore its association with academic self-concept have rarely distinguished between subjects involved (e.g., mathematics or language learning). Moreover, some processes taking place during forced social comparison are thought to have a negative impact on academic self-concept. Thus, the aims of this study were to explore: 1) the associations between self-concepts (i.e., Language learning, Mathematics and Social), attitudes towards school and social comparison processes in school settings; and 2) the influence of social comparison processes on components of academic self-concept across gender. A sample of 238 elementary school students (Mage= 10.12, SD = 1.25; 52% boys) completed a questionnaire assessing self-concepts and attitudes towards school, as well as a questionnaire measuring four social comparison processes. Results indicated that girls used negative processes (i.e., upward contrast and downward identification) more than boys. In addition, boys reported better self-concept in mathematics while girls reported better self-concept in language learning (small effect). Results of stepwise multiple linear regression analyses showed that upward contrast best explained gender differences, with a stronger effect for girls. Attitudes towards school only explained gender differences in language learning self-concept. Furthermore, positive processes (i.e., upward identification and downward contrast) have no effect on either component of academic self-concept. Results of this study demonstrate the need to examine the evolution of social comparison processes over time, considering their impact on students’ academic/social well-being and achievement from a gender perspective.
Multistep Structural and Chemical Evaluation of Sugarcane Baggase, Pretreated With Alkali for Enhancing the Enzymatic Saccharification by Cellulase and Xylanase of the Pseudomonas sp. CVB-10 (MK443365) and Bacillus paramycoides T4 (MN370035) Mix-Culture System
Authors: Tiwari Soni , Yadav Janardan , Gaur Rajeeva , Singh Ranjan , Verma Tuhina , Yadav Jay Shanker , Pandey Prabhash Kumar , Rath Srikanta Kumar
Published: January 2022

The enzymatic saccharification of sugarcane bagasse was significantly increased by alkali pretreatment under mild conditions. The effectiveness of different concentrations of alkali and acid pretreatment of sugarcane bagasse for improving the enzymatic saccharification of lignocellulose has been evaluated. The sugarcane bagasse was characterized to contain 39.52% celluloses, 25.63% hemicelluloses, and 30.36% lignin. After that, sugarcane bagasse was pretreated with 5 and 10% of H2SO4 and NaOH at 121°C for 60 min. FTIR, XRD, and SEM analyses also showed significant molecular and surface structure changes of the sugarcane bagasse with 10% NaOH. Maximum saccharification was 489.5 mg/g from 10% NaOH pretreatment followed by 322.75, 301.25, and 276.6 mg/g from 10% H2SO4, 5% NaOH, and 5% H2SO4, respectively, which were 55.1, 32.0, 27.1, and 20.6 times higher than the that of the control. Cellulase and xylanase produced by Pseudomonas sp. CVB-10 (MK443365) and Bacillus paramycoides T4 (MN370035) were used to hydrolyze the pretreated bagasse, and the optimal condition was determined to be 30 h of the enzymatic reaction with the 3:1 ratio of enzymes under the temperature of 55°C, pH 5.0, and substrate concentration of 3%, leading to celluloses and hemicelluloses conversion in the enzymatic hydrolysis/saccharification that is more proficient.
Development and Validation of a Tumor Mutation Burden-Related Immune Prognostic Signature for Ovarian Cancers
Authors: Cui Mengjing , Xia Qianqian , Zhang Xing , Yan Wenjing , Meng Dan , Xie Shuqian , Shen Siyuan , Jin Hua , Wang Shizhi
Published: January 2022

Ovarian cancer (OC), one of the most common malignancies of the female reproductive system, is characterized by high incidence and poor prognosis. Tumor mutation burden (TMB), as an important biomarker that can represent the degree of tumor mutation, is emerging as a key indicator for predicting the efficacy of tumor immunotherapy. In our study, the gene expression profiles of OC were downloaded from TCGA and GEO databases. Subsequently, we analyzed the prognostic value of TMB in OC and found that a higher TMB score was significantly associated with a better prognosis (p = 0.004). According to the median score of TMB, 9 key TMB related immune prognostic genes were selected by LASSO regression for constructing a TMB associated immune risk score (TMB-IRS) signature, which can effectively predict the prognosis of OC patients (HR = 2.32, 95% CI = 1.68–3.32; AUC = 0.754). Interestingly, TMB-IRS is also closely related to the level of immune cell infiltration and immune checkpoint molecules (PD1, PD-L1, CTLA4, PD-L2) in OC. Furthermore, the nomogram combined with TMB-IRS and a variety of clinicopathological features can more comprehensively evaluate the prognosis of patients. In conclusion, we explored the relationship between TMB and prognosis and validated the TMB-IRS signature based on TMB score in an independent database (HR = 1.60, 95% CI = 1.13–2.27; AUC = 0.639), which may serve as a novel biomarker for predicting OC prognosis as well as possible therapeutic targets.
Promoter DNA Methylation in GWAS-Identified Genes as Potential Functional Elements for Blood Pressure: An Observational and Mendelian Randomization Study
Authors: Zhang Huan , Wang Aili , Xu Tan , Mo Xingbo , Zhang Yonghong
Published: January 2022

Genome-wide association studies have identified numerous genetic loci for blood pressure (BP). However, the relationships of functional elements inside these loci with BP are not fully understood. This study represented an effort to determine if promoter DNA methylations inside BP-associated loci were associated with BP.We conducted a cross-sectional study investigating the association between promoter DNA methylations of 10 candidate genes and BP in 1,241 Chinese individuals. Twenty-one genomic fragments in the CpG Islands were sequenced. The associations of methylation levels with BP and hypertension were assessed in regression models. Mendelian randomization (MR) analysis was then applied to find supporting evidence for the identified associations.A total of 413 DNA methylation sites were examined in an observational study. Methylation levels of 24 sites in PRDM6, IGFBP3, SYT7, PDE3A, TBX2 and C17orf82 were significantly associated with BP. Methylation levels of PRDM6 and SYT7 were significantly associated with hypertension. Methylation levels of five sites (including cg06713098) in IGFBP3 were significantly associated with DBP. MR analysis found associations between the methylation levels of six CpG sites (cg06713098, cg14228300, cg23193639, cg21268650, cg10677697 and cg04812164) around the IGFBP3 promoter and DBP. Methylation levels of cg14228300 and cg04812164 were associated with SBP. By further applying several MR methods we showed that the associations may not be due to pleiotropy. Association between IGFBP3 mRNA levels in blood cells and BP was also found in MR analysis. This study identified promoter methylation as potential functional element for BP. The identified methylations may be involved in the regulatory pathway linking genetic variants to BP.
Naringenin Regulates FKBP4/NR3C1/NRF2 Axis in Autophagy and Proliferation of Breast Cancer and Differentiation and Maturation of Dendritic Cell
Authors: Xiong Hanchu , Chen Zihan , Lin Baihua , Xie Bojian , Liu Xiaozhen , Chen Cong , Li Zhaoqing , Jia Yunlu , Wu Zhuazhua , Yang Min , Jia Yongshi , Wang Linbo , Zhou Jichun , Meng Xuli
Published: January 2022

NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.
Tissue Trafficking Kinetics of Rhesus Macaque Natural Killer Cells Measured by Serial Intravascular Staining
Authors: Mortlock Ryland D. , Wu Chuanfeng , Potter E. Lake , Abraham Diana M. , Allan David S. J. , Hong So Gun , Roederer Mario , Dunbar Cynthia E.
Published: January 2022

The in vivo tissue distribution and trafficking patterns of natural killer (NK) cells remain understudied. Animal models can help bridge the gap, and rhesus macaque (RM) primates faithfully recapitulate key elements of human NK cell biology. Here, we profiled the tissue distribution and localization patterns of three NK cell subsets across various RM tissues. We utilized serial intravascular staining (SIVS) to investigate the tissue trafficking kinetics at steady state and during recovery from CD16 depletion. We found that at steady state, CD16+ NK cells were selectively retained in the vasculature while CD56+ NK cells had a shorter residence time in peripheral blood. We also found that different subsets of NK cells had distinct trafficking kinetics to and from the lymph node as well as other lymphoid and non-lymphoid tissues. Lastly, we found that following administration of CD16-depleting antibody, CD16+ NK cells and their putative precursors retained a high proportion of continuously circulating cells, suggesting that regeneration of the CD16 NK compartment may take place in peripheral blood or the perivascular compartments of tissues.
Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma
Authors: Rodríguez-García Alba , Linares María , Morales María Luz , Allain-Maillet Sophie , Mennesson Nicolas , Sanchez Ricardo , Alonso Rafael , Leivas Alejandra , Pérez-Rivilla Alfredo , Bigot-Corbel Edith , Hermouet Sylvie , Martínez-López Joaquín
Published: January 2022

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.
Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of ‘Almost Natural’ Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection
Authors: Klewinghaus Daniel , Pekar Lukas , Arras Paul , Krah Simon , Valldorf Bernhard , Kolmar Harald , Zielonka Stefan
Published: January 2022

A subset of antibodies found in cattle comprises ultralong CDR-H3 regions of up to 70 amino acids. Interestingly, this type of immunoglobulin usually pairs with the single germline VL gene, V30 that is typically very conserved in sequence. In this work, we have engineered ultralong CDR-H3 common light chain bispecific antibodies targeting Epidermal Growth Factor Receptor (EGFR) on tumor cells as well as Natural Cytotoxicity Receptor NKp30 on Natural Killer (NK) cells. Antigen-specific common light chain antibodies were isolated by yeast surface display by means of pairing CDR-H3 diversities following immunization with a single V30 light chain. After selection, EGFR-targeting paratopes as well as NKp30-specific binders were combined into common light chain bispecific antibodies by exploiting the strand-exchange engineered domain (SEED) technology for heavy chain heterodimerization. Biochemical characterization of resulting bispecifics revealed highly specific binding to the respective antigens as well as simultaneous binding to both targets. Most importantly, engineered cattle-derived bispecific common light chain molecules elicited potent NK cell redirection and consequently tumor cell lysis of EGFR-overexpressing cells as well as robust release of proinflammatory cytokine interferon-γ. Taken together, this data is giving clear evidence that bovine bispecific ultralong CDR-H3 common light chain antibodies are versatile for biotechnological applications.
LncRNAs and Rheumatoid Arthritis: From Identifying Mechanisms to Clinical Investigation
Authors: Huang Wentao , Li Xue , Huang Chen , Tang Yukuan , Zhou Quan , Chen Wenli
Published: January 2022

Rheumatoid arthritis (RA) is a systemic chronic autoinflammatory disease, and the synovial hyperplasia, pannus formation, articular cartilage damage and bone matrix destruction caused by immune system abnormalities are the main features of RA. The use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) has achieved great advances in the therapy of RA. Yet there are still patients facing the problem of poor response to drug therapy or drug intolerance. Current therapy methods can only moderate RA progress, but cannot stop or reverse the damage it has caused. Recent studies have reported that there are a variety of long non-coding RNAs (LncRNAs) that have been implicated in mediating many aspects of RA. Understanding the mechanism of LncRNAs in RA is therefore critical for the development of new therapy strategies and prevention strategies. In this review, we systematically elucidate the biological roles and mechanisms of action of LncRNAs and their mechanisms of action in RA. Additionally, we also highlight the potential value of LncRNAs in the clinical diagnosis and therapy of RA.
The Application of Tannic Acid in Orthopedics
Authors: Sun Yingchuan , Qu Yang , Zhao Jianwu
Published: January 2022

Tannic acid (TA) is a naturally occurring polyphenol compound commonly found in tea, wine, and fruits. Because of the excellent structural and functional properties afforded by TA, materials based on the structure of polyhydroxyphenols have great value, particularly for orthopedic transplantation. This compound, for example, can form a strong interaction with metals and can form a stable coating on their surfaces, thus, improving the physical and chemical properties of bone–implant surfaces and boosting implantation success rates. TA can also inhibit the activity of osteoclasts, thus, playing a potential role in the treatment of osteoporosis. Furthermore, if the body becomes polluted with heavy metals, TA can chelate the ions to protect bone morphology and structure. It also has a significant antibacterial effect and can reduce infections caused by surgical implantation and inhibit a variety of tumor cells, thereby promoting its potential application in spinal metastasis surgery. Furthermore, it can also slow the corrosion caused by magnesium alloys, thereby greatly improving the development of degradable orthopedic metal fixatives. Importantly, TA is cheap and easy to obtain, making it extremely valuable for use in orthopedics. This review focuses on the research status and practical applications of TA, and prospects for its future application for orthopedics (Figure 1).
Age-Related Risk Factors and Complications of Patients With COVID-19: A Population-Based Retrospective Study
Authors: Zhang Han , Wu Yingying , He Yuqing , Liu Xingyuan , Liu Mingqian , Tang Yuhong , Li Xiaohua , Yang Guang , Liang Gang , Xu Shabei , Wang Minghuan , Wang Wei
Published: January 2022

Objective: To study the differences in clinical characteristics, risk factors, and complications across age-groups among the inpatients with the coronavirus disease 2019 (COVID-19).

Methods: In this population-based retrospective study, we included all the positive hospitalized patients with COVID-19 at Wuhan City from December 29, 2019 to April 15, 2020, during the first pandemic wave. Multivariate logistic regression analyses were used to explore the risk factors for death from COVID-19. Canonical correlation analysis (CCA) was performed to study the associations between comorbidities and complications.

Results: There are 36,358 patients in the final cohort, of whom 2,492 (6.85%) died. Greater age (odds ration [OR] = 1.061 [95% CI 1.057–1.065], p < 0.001), male gender (OR = 1.726 [95% CI 1.582–1.885], p < 0.001), alcohol consumption (OR = 1.558 [95% CI 1.355–1.786], p < 0.001), smoking (OR = 1.326 [95% CI 1.055–1.652], p = 0.014), hypertension (OR = 1.175 [95% CI 1.067–1.293], p = 0.001), diabetes (OR = 1.258 [95% CI 1.118–1.413], p < 0.001), cancer (OR = 1.86 [95% CI 1.507–2.279], p < 0.001), chronic kidney disease (CKD) (OR = 1.745 [95% CI 1.427–2.12], p < 0.001), and intracerebral hemorrhage (ICH) (OR = 1.96 [95% CI 1.323–2.846], p = 0.001) were independent risk factors for death from COVID-19. Patients aged 40–80 years make up the majority of the whole patients, and them had similar risk factors with the whole patients. For patients aged <40 years, only cancer (OR = 17.112 [95% CI 6.264–39.73], p < 0.001) and ICH (OR = 31.538 [95% CI 5.213–158.787], p < 0.001) were significantly associated with higher odds of death. For patients aged >80 years, only age (OR = 1.033 [95% CI 1.008–1.059], p = 0.01) and male gender (OR = 1.585 [95% CI 1.301–1.933], p < 0.001) were associated with higher odds of death. The incidence of most complications increases with age, but arrhythmias, gastrointestinal bleeding, and sepsis were more common in younger deceased patients with COVID-19, with only arrhythmia reaching statistical difference (p = 0.039). We found a relatively poor correlation between preexisting risk factors and complications.

Conclusions: Coronavirus disease 2019 are disproportionally affected by age for its clinical manifestations, risk factors, complications, and outcomes. Prior complications have little effect on the incidence of extrapulmonary complications.
Development of Immunochromatographic Assay for the Rapid Detection of Mycoplasma capricolum subsp. capripneumoniae Antibodies
Authors: Zhu Zhen , Qu Guanggang , Wang Changjiang , Wang Lei , Du Jige , Li Qianlin , Shen Zhiqiang , Chen Xiaoyun
Published: January 2022

Mycoplasma capricolum subsp. capripneumoniae (Mccp) is the cause of contagious caprine pleuropneumonia (CCPP), which is a highly significant respiratory disease in goats leading to significant economic losses in Africa and Asia. Currently available procedures for the diagnosis of CCPP have some limitations in sensitivity, specificity, operation time, requirement of sophisticated equipment or skilled personnel, and cost. In this study, we developed a rapid, sensitive, and specific colloidal gold-based immunochromatographic assay (GICA) strip for the efficient on-site detection of antibodies against Mccp in the serum within 10 min. For the preparation of this colloidal GICA strip, recombinant P20 protein, the membrane protein of Mccp, was expressed by Escherichia coli prokaryotic expression system after purification was used as the binding antigen in the test. The rabbit anti-goat immunoglobulin G labeled with the colloidal gold was used as the detection probe, whereas the goat anti-rabbit immunoglobulin G was coated on the nitrocellulose membrane as the control line. The concentration of the coating antibody was optimized, and the effectiveness of this colloidal GICA strip was evaluated. Our results proved that the detection limit of the test strip was up to 1:64 dilutions for the Mccp antibody-positive serum samples with no cross-reactivity with other pathogens commonly infecting small ruminants,including goat pox virus, peste des petits ruminants virus, foot-and-mouth disease virus type A, or other mycoplasmas. Moreover, the colloidal GICA strip was more sensitive and specific than the indirect hemagglutination assay for the detection of Mccp antibodies. The 106 clinical serum samples were detected by the colloidal GICA strip compared with the complement fixation test, demonstrating an 87.74% concordance with the complement fixation test. This novel colloidal GICA strip would be an effective tool for the cost-effective and rapid diagnosis of CCPP in the field.
Detection and Quantification of Stagonosporopsis cucurbitacearum in Seeds of Cucurbita maxima Using Droplet Digital Polymerase Chain Reaction
Authors: Murolo Sergio , Moumni Marwa , Mancini Valeria , Allagui Mohamed Bechir , Landi Lucia , Romanazzi Gianfranco
Published: January 2022

Stagonosporopsis cucurbitacearum is an important seedborne pathogen of squash (Cucurbita maxima). The aim of our work was to develop a rapid and sensitive diagnostic tool for detection and quantification of S. cucurbitacearum in squash seed samples, to be compared with blotter analysis, that is the current official seed test. In blotter analysis, 29 of 31 seed samples were identified as infected, with contamination from 1.5 to 65.4%. A new set of primers (DB1F/R) was validated in silico and in conventional, quantitative real-time PCR (qPCR) and droplet digital (dd) PCR. The limit of detection of S. cucurbitacearum DNA for conventional PCR was ∼1.82 × 10–2 ng, with 17 of 19 seed samples positive. The limit of detection for ddPCR was 3.6 × 10–3 ng, which corresponded to 0.2 copies/μl. Detection carried out with artificial samples revealed no interference in the absolute quantification when the seed samples were diluted to 20 ng. All seed samples that showed S. cucurbitacearum contamination in the blotter analysis were highly correlated with the absolute quantification of S. cucurbitacearum DNA (copies/μl) in ddPCR (R2 = 0.986; p ≤ 0.01). Our ddPCR protocol provided rapid detection and absolute quantification of S. cucurbitacearum, offering a useful support to the standard procedure.
The Effect of Salmon Food-Derived DOM and Glacial Melting on Activity and Diversity of Free-Living Bacterioplankton in Chilean Patagonian Fjords
Authors: Montero Paulina , Gutiérrez Marcelo H. , Daneri Giovanni , Jacob Bárbara
Published: January 2022

Fjord ecosystems cycle and export significant amounts of carbon and appear to be extremely sensitive to climate change and anthropogenic perturbations. To identify patterns of microbial responses to ongoing natural and human-derived changes in the fjords of Chilean Patagonia, we examined the effect of organic enrichment associated with salmon aquaculture and freshening produced by glacial melting on bacterial production (BP), extracellular enzymatic activity (EEA), and community diversity of free-living bacterioplankton. We assayed the effects of salmon food-derived dissolved organic matter (SF-DOM) and meltwaters through microcosm experiments containing waters from Puyuhuapi Fjord and the proglacial fjords of the Southern Patagonia Icefield, respectively. Rates of BP and EEA were 2 times higher in the presence of SF-DOM than in controls, whereas the addition of autochthonous organic matter derived from diatoms (D-DOM) resulted in rates of BP and EEA similar to those measured in the controls. The addition of SF-DOM also reduced species richness and abundance of a significant fraction of the representative taxa of bacterioplankton of Puyuhuapi Fjord. In the proglacial fjords, bacterioplankton diversity was reduced in areas more heavily influenced by meltwaters and was accompanied by moderate positive changes in BP and EEA. Our findings strongly suggest that SF-DOM is highly reactive, promoting enhanced rates of microbial activity while could be influencing the diversity of bacterioplankton communities in Patagonian fjords with a strong salmon farming activity. These findings challenge the traditional view of phytoplankton production as the primary source of labile DOM that fuels heterotrophic activity in coastal ecosystems impacted by anthropogenic organic enrichment. Given the intensive local production of salmon, we analyze the significance of this emerging source of rich “allochthonous” organic substrates for autotrophic/heterotrophic balance, carbon exportation, and hypoxia in Patagonian fjords. The effect of human DOM enrichment can be enhanced in proglacial fjords, where progressive glacial melting exerts additional selective pressure on bacterioplankton diversity.
Effects of Compound Probiotics on Cecal Microbiome and Metabolome of Shaoxing Duck
Authors: Sun Hanxue , Du Xizhong , Zeng Tao , Ruan Shenggang , Li Guoqin , Tao Zhengrong , Xu Wenwu , Lu Lizhi
Published: January 2022

This experiment was conducted to investigate the effects of compound probiotics on intestinal microflora and metabolome of Shaoxing ducks. A total of 640 1-day-old Shaoxing ducks were randomly divided into two treatments with eight replicates and forty ducks for each replicate. The ducks were fed basal diet (Ctrl) and basal diet supplemented with 0.15% compound probiotics (MixP). The experiment lasted for 85 days. The results showed that the abundance of Bacteroidetes and Bacteroides in MixP was higher than that in Ctrl (P < 0.05). However, the abundance of Firmicutes and Oscillospira and Desulfovibrio in MixP was lower than that in Ctrl (P < 0.05). Concentrations of 71 metabolites differed significantly (P < 0.05) between the MixP and the Ctrl groups; for example, Pyridoxal (Vitamin B6), L-Arginine, and Betaine aldehyde were up-regulated (P < 0.05), and 7-oxocholesterol, 3-hydroxy-L-kynureni-ne, and N-acetyl-d-glucosamine were down-regulated (P < 0.05). KEGG was enriched in 15 metabolic pathways. The pathways of Vitamin B6 metabolism, Vascular smooth muscle contraction, Vitamin digestion and absorption, and Protein digestion and absorption were influenced by compound probiotics supplementation. Thus, supplementation of compound probiotics improved cecal heath through shifts in the cecal microbiome and metabolome.
Effects of Salinity on the Biodegradation of Polycyclic Aromatic Hydrocarbons in Oilfield Soils Emphasizing Degradation Genes and Soil Enzymes
Authors: Li Yang , Li Wenjing , Ji Lei , Song Fanyong , Li Tianyuan , Fu Xiaowen , Li Qi , Xing Yingna , Zhang Qiang , Wang Jianing
Published: January 2022

The biodegradation of organic pollutants is the main pathway for the natural dissipation and anthropogenic remediation of polycyclic aromatic hydrocarbons (PAHs) in the environment. However, in the saline soils, the PAH biodegradation could be influenced by soil salts through altering the structures of microbial communities and physiological metabolism of degradation bacteria. In the worldwide, soils from oilfields are commonly threated by both soil salinity and PAH contamination, while the influence mechanism of soil salinity on PAH biodegradation were still unclear, especially the shifts of degradation genes and soil enzyme activities. In order to explain the responses of soils and bacterial communities, analysis was conducted including soil properties, structures of bacterial community, PAH degradation genes and soil enzyme activities during a biodegradation process of PAHs in oilfield soils. The results showed that, though low soil salinity (1% NaCl, w/w) could slightly increase PAH degradation rate, the biodegradation in high salt condition (3% NaCl, w/w) were restrained significantly. The higher the soil salinity, the lower the bacterial community diversity, copy number of degradation gene and soil enzyme activity, which could be the reason for reductions of degradation rates in saline soils. Analysis of bacterial community structure showed that, the additions of NaCl increase the abundance of salt-tolerant and halophilic genera, especially in high salt treatments where the halophilic genera dominant, such as Acinetobacter and Halomonas. Picrust2 and redundancy analysis (RDA) both revealed suppression of PAH degradation genes by soil salts, which meant the decrease of degradation microbes and should be the primary cause of reduction of PAH removal. The soil enzyme activities could be indicators for microorganisms when they are facing adverse environmental conditions.
Variation and Variability in Drosophila Grooming Behavior
Authors: Mueller Joshua M. , Zhang Neil , Carlson Jean M. , Simpson Julie H.
Published: January 2022

Behavioral differences can be observed between species or populations (variation) or between individuals in a genetically similar population (variability). Here, we investigate genetic differences as a possible source of variation and variability in Drosophila grooming. Grooming confers survival and social benefits. Grooming features of five Drosophila species exposed to a dust irritant were analyzed. Aspects of grooming behavior, such as anterior to posterior progression, were conserved between and within species. However, significant differences in activity levels, proportion of time spent in different cleaning movements, and grooming syntax were identified between species. All species tested showed individual variability in the order and duration of action sequences. Genetic diversity was not found to correlate with grooming variability within a species: melanogaster flies bred to increase or decrease genetic heterogeneity exhibited similar variability in grooming syntax. Individual flies observed on consecutive days also showed grooming sequence variability. Standardization of sensory input using optogenetics reduced but did not eliminate this variability. In aggregate, these data suggest that sequence variability may be a conserved feature of grooming behavior itself. These results also demonstrate that large genetic differences result in distinguishable grooming phenotypes (variation), but that genetic heterogeneity within a population does not necessarily correspond to an increase in the range of grooming behavior (variability).
Muscarinic Acetylcholine Receptor Localization on Distinct Excitatory and Inhibitory Neurons Within the ACC and LPFC of the Rhesus Monkey
Authors: Tsolias Alexandra , Medalla Maria
Published: January 2022

Acetylcholine (ACh) can act on pre- and post-synaptic muscarinic receptors (mAChR) in the cortex to influence a myriad of cognitive processes. Two functionally-distinct regions of the prefrontal cortex—the lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC)—are differentially innervated by ascending cholinergic pathways yet, the nature and organization of prefrontal-cholinergic circuitry in primates are not well understood. Using multi-channel immunohistochemical labeling and high-resolution microscopy, we found regional and laminar differences in the subcellular localization and the densities of excitatory and inhibitory subpopulations expressing m1 and m2 muscarinic receptors, the two predominant cortical mAChR subtypes, in the supragranular layers of LPFC and ACC in rhesus monkeys (Macaca mulatta). The subset of m1+/m2+ expressing SMI-32+ pyramidal neurons labeled in layer 3 (L3) was denser in LPFC than in ACC, while m1+/m2+ SMI-32+ neurons co-expressing the calcium-binding protein, calbindin (CB) was greater in ACC. Further, we found between-area differences in laminar m1+ dendritic expression, and m2+ presynaptic localization on cortico-cortical (VGLUT1+) and sub-cortical inputs (VGLUT2+), suggesting differential cholinergic modulation of top-down vs. bottom-up inputs in the two areas. While almost all inhibitory interneurons—identified by their expression of parvalbumin (PV+), CB+, and calretinin (CR+)—expressed m1+, the localization of m2+ differed by subtype and area. The ACC exhibited a greater proportion of m2+ inhibitory neurons compared to the LPFC and had a greater density of presynaptic m2+ localized on inhibitory (VGAT+) inputs targeting proximal somatodendritic compartments and axon initial segments of L3 pyramidal neurons. These data suggest a greater capacity for m2+-mediated cholinergic suppression of inhibition in the ACC compared to the LPFC. The anatomical localization of muscarinic receptors on ACC and LPFC micro-circuits shown here contributes to our understanding of diverse cholinergic neuromodulation of functionally-distinct prefrontal areas involved in goal-directed behavior, and how these interactions maybe disrupted in neuropsychiatric and neurological conditions.
Drug Use in Night Owls May Increase the Risk for Mental Health Problems
Authors: Fernando Jeevan , Stochl Jan , Ersche Karen D.
Published: January 2022

Drugs of abuse are widely known to worsen mental health problems, but this relationship may not be a simple causational one. Whether or not a person is susceptible to the negative effects of drugs of abuse may not only be determined by their addictive properties, but also the users’ chronotype, which determines their daily activity patterns. The present study investigates the relationship between chronotype, drug use and mental health problems in a cross-sectional community sample. Participants (n = 209) completed a selection of questionnaires online, including the Munich Chronotype Questionnaire, the Depression Anxiety Stress Scale, the Alcohol Use Disorder Identification Test, the Cannabis Use Disorder Identification Test and the Fagerström Test for Nicotine Dependence. We conducted multiple regression models to determine relationships between participants’ chronotype and their reported mental health symptoms and then estimated mediation models to investigate the extent to which their drug consumption accounted for the identified associations. Chronotype was significantly associated with participants’ overall mental health (β = 0.16, p = 0.022) and their anxiety levels (β = 0.18, p = 0.009) but not with levels of depression or stress. However, both relationships were fully mediated by participants’ overall drug consumption. Thus, late chronotypes, so-called “night owls”, not only use more drugs but consequently have an increased risk for developing anxiety and deteriorating mental health status. This group may be particularly vulnerable to the negative psychological effects of drugs. Our results point toward the importance of considering chronotype in designing preventative and therapeutic innovations, specifically for anxiety, which at present has been largely neglected.
Nomogram to Predict Intensive Care Following Gastrectomy for Gastric Cancer: A Useful Clinical Tool to Guide the Decision-Making of Intensive Care Unit Admission
Authors: Pan Tao , Chen Xiao-long , Liu Kai , Peng Bo-qiang , Zhang Wei-han , Yan Meng-hua , Ge Rui , Zhao Lin-yong , Yang Kun , Chen Xin-zu , Hu Jian-kun
Published: January 2022

Background

We aimed to generate and validate a nomogram to predict patients most likely to require intensive care unit (ICU) admission following gastric cancer surgery to improve postoperative outcomes and optimize the allocation of medical resources.

Methods

We retrospectively analyzed 3,468 patients who underwent gastrectomy for gastric cancer from January 2009 to June 2018. Here, 70.0% of the patients were randomly assigned to the training cohort, and 30.0% were assigned to the validation cohort. Least absolute shrinkage and selection operator (LASSO) method was performed to screen out risk factors for ICU-specific care using the training cohort. Then, based on the results of LASSO regression analysis, multivariable logistic regression analysis was performed to establish the prediction nomogram. The calibration and discrimination of the nomogram were evaluated in the training cohort and validated in the validation cohort. Finally, the clinical usefulness was determined by decision curve analysis (DCA).

Results

Age, the American Society of Anesthesiologists (ASA) score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were selected for the model. The concordance index (C-index) of the model was 0.843 in the training cohort and 0.831 in the validation cohort. The calibration curves of the ICU-specific care risk nomogram suggested great agreement in both training and validation cohorts. The DCA showed that the nomogram was clinically useful.

Conclusions

Age, ASA score, chronic pulmonary disease, heart disease, hypertension, combined organ resection, and preoperative and/or intraoperative blood transfusions were identified as risk factors for ICU-specific care after gastric surgery. A clinically friendly model was generated to identify those most likely to require intensive care.
Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA
Authors: Fenqi Du , Yupeng Liu , Qiuju Zhang , Chao Yuan , Wenjie Song , Tianyi Xia , Junnan Guo , Weinan Xue , Xiufeng Jiang , Junge Bai , Chenyang Jia , Hua Xi , Yien Li , Xuefeng Bai , Yanlong Liu
Published: January 2022

Background

Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.

Methods

Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.

Results

We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient’s prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).

Conclusions

Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.