bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Local Correlations Among Causal Factor Classifications as a Strategy to Improve Landslide Susceptibility Mapping
Authors: Xiao Ting , Yu Lanbing , Tian Weiming , Zhou Chang , Wang Luqi
Published: November 2021

A landslide susceptibility map (LSM) is the basis of hazard and risk assessment, guiding land planning and utilization, early warning of disaster, etc. Researchers are often overly keen on hybridizing state-of-the-art models or exploring new mathematical susceptibility models to improve the accuracy of the susceptibility map in terms of a receiver operator characteristic curve. Correlation analysis of the causal factors is a necessary routine process before susceptibility modeling to ensure that the overall correlation among all factors is low. However, this overall correlation analysis is insufficient to detect a high local correlation among the causal factor classes. The objective of this study is to answer three questions: 1) Is there a high correlation between causal factors in some parts locally? 2) Does it affect the accuracy of landslide susceptibility assessment? and 3) How can this influence be eliminated? To this aim, Wanzhou County was taken as the test site, where landslide susceptibility assessment based on 12 causal factors has been previously performed using the frequency ratio (FR) model and random forest (RF) model. In this work, we conducted a local spatial correlation analysis of the “altitude” and “rivers” factors and found a sizeable spatial overlap between altitude-class-1 and rivers-class-1. The “altitude” and “rivers” factors were reclassified, and then the FR model and RF model were used to reevaluate the susceptibility and analyze the accuracy loss caused by the local spatial correlation of the two factors. The results demonstrated that the accuracy of LSMs was markedly enhanced after reclassification of “altitude” and “rivers,” especially for the RF model–based LSM. This research shed new light on the local correlation of causal factors arising from a particular geomorphology and their impact on susceptibility.
Maximum Thickness Location Selection of High Subsonic Axial Compressor Airfoils and Its Effect on Aerodynamic Performance
Authors: Tao Chuansijia , Du Xin , Ding Jun , Luo Yizhou , Wang Zhongqi
Published: November 2021

Solidity and camber angle are key parameters with a primary effect on airfoil diffusion. Maximum thickness location has a considerable impact on blade loading distribution. This paper investigates correlations of maximum thickness location, solidity, and camber angle with airfoil performance to choose maximum thickness location quickly for compressor airfoils with different diffusion. The effects of maximum thickness location, solidity, and camber angle on incidence characteristics are discussed based on abundant two-dimensional cascade cases computed through numerical methods. Models of minimum loss incidence, total pressure loss coefficient, diffusion factor, and static pressure rise coefficient are established to describe correlations quantitatively. Based on models, dependence maps of total pressure loss coefficient, diffusion factor, and static pressure rise coefficient are drawn and total loss variation brought by maximum thickness location is analyzed. The study shows that the preferred selection of maximum thickness location can be the most forward one with no serious shock loss. Then, the choice maps of optimal maximum thickness location on different design conditions are presented. The optimal maximum thickness locates at 20–35% chord length. Finally, a database of optimal cases which can meet different loading requirements is provided as a tool for designers to choose geometrical parameters.
Modeling the Heat-Hydrogen Balance Characteristic of Hydrogen Energy Storage and Cooperative Dispatch of Wind-Hydrogen Hybrid System
Authors: Si Yang , Chen Laijun , Ma Linrui , Gao Mengyu , Ma Hengrui , Mei Shengwei
Published: November 2021

The heat and hydrogen balance of the hydrogen energy storage system’s intermittent operation becomes a key factor affecting the performance of the wind-hydrogen hybrid system (W-HHS). This work designed a hydrogen energy storage system (HESS), including waste heat utilization. Then, a dual state of charge (SOC) model is established, in which hydrogen and heat storage is considered. Furthermore, based on the distributionally robust method, an optimal dispatch method of W-HHS is proposed to reduce the operation cost of conventional units in the grid and increase the revenue of the W-HHS. The previously proposed dual SOC model of heat-hydrogen balance is regarded as a constraint in this cooperative dispatch. The effectiveness and efficiency of the dual SOC model were verified on the IEEE 30-bus system with an actual wind plant data set. The results show that the hydrogen-heat dual SOC model can fully reflect the influence of heat and hydrogen balance on the operation of the W-HHS. The cooperative dispatch method improves the reliability of the W-HHS operation under the premise of ensuring the heat-hydrogen balance. When the constraints of hydrogen balance SOC and heat balance SOC are met simultaneously, the available power of the wind plant is 6–8% lower than the ideal situation. Parameter analysis indicates that reducing the heat dissipation coefficient can reduce the influence of the SOC constraint of heat balance on the dispatch strategy and increase the power output of the wind plant. When the heat dissipation coefficient is less than 1/1,200, the heat balance SOC constraint fails.
Time for Science-Based National Targets for Environmental Sustainability: An Assessment of Existing Metrics and the ESGAP Framework
Authors: Usubiaga-Liaño Arkaitz , Ekins Paul
Published: November 2021

Despite the overwhelming scientific evidence on the ongoing degradation of the environment, there is a clear gap between the urgency of the environmental crisis and the policy measures put in place to tackle it. Because of the role of metrics in environmental governance, the way environmental information is translated into metrics is of utmost relevance. In this context, we propose criteria to assesses the suitability of environmental metrics to monitor environmental sustainability at the national level. After assessing well-known environmental metrics such as the Sustainable Development Goals indicators and the Environmental Performance Index, we conclude that countries still lack robust and resonant metrics to monitor environmental sustainability. In order to bridge this metric gap, we present the Environmental Sustainability Gap (ESGAP) framework, which builds on the concepts of strong sustainability, critical natural capital, environmental functions and science-based targets. Different composite indicators are proposed as part of the ESGAP framework. Through these metrics, the framework has the potential to embed strong sustainability thinking and science-based targets in nations in which these concepts are not currently sufficiently reflected in policies.
Detection of Cryptic Sex in Automictic Populations: Theoretical Expectations and a Case Study in Cataglyphis Desert Ants
Authors: Kuhn Alexandre , Aron Serge , Hardy Olivier J.
Published: November 2021

Reproductive strategies are diverse and a whole continuum of mixed systems lies between strict sexuality and strict clonality (apomixis), including automixis, a parthenogenetic mode of reproduction involving a meiosis and increasing homozygosity over generations. These various systems impact the genetic structure of populations, which can therefore be used to infer reproductive strategies in natural populations. Here, we first develop a mathematical model, validated by simulations, to predict heterozygosity and inbreeding in mixed sexual-automictic populations. It highlights the predominant role of the rate of heterozygosity loss experienced during automixis (γ), which is locus dependent. Whenγis low, mixed populations behave like purely sexual ones until sex becomes rare. In contrast, whenγis high, the erosion of genetic diversity is tightly correlated to the rate of sex, so that the individual inbreeding coefficient can inform on the ratio of sexual/asexual reproduction. In the second part of this study, we used our model to test the presence of cryptic sex in a hybridogeneticCataglyphisant where new queens are produced parthenogenetically, leaving males with an apparent null fitness while they are essential to colony development as sperm is required to produce workers. Occasional sexual production of queens could resolve this paradox by providing males some fertile progeny. To determine whether this occurs in natural populations, we simulated genotypic datasets in a population under various regimes of sexual vs. asexual reproduction for queen production and compared the distribution of inbreeding, expected heterozygosity and inter-individual relatedness coefficients with those observed in a natural population ofCataglyphis mauritanicausing microsatellites. Our simulations show that the distribution of inter-individual relatedness coefficients was particularly informative to assess the relative rate of sexual/asexual reproduction, and our dataset was compatible with pure parthenogenesis but also with up to 2% sexual reproduction. Our approach, implemented in an R script, should be useful to assess reproductive strategies in other biological models.
High Expression of C1ORF112 Predicts a Poor Outcome: A Potential Target for the Treatment of Low-Grade Gliomas
Authors: Zhang Zhe , Tan Zilong , Lv Qiaoli , Wang Lichong , Yu Kai , Yang Huan , Liang Huaizhen , Lu Tianzhu , Ji Yulong , Chen Junjun , He Wei , Chen Zhen , Chen Shuhui , Shen Xiaoli
Published: November 2021

Background: Glioma is the most common primary tumor of the central nervous system and is associated with poor overall survival, creating an urgent need to identify survival-associated biomarkers. C1ORF112, an alpha-helical protein, is overexpressed in some cancers; however, its prognostic role has not yet been explored in gliomas. Thus, in this study, we attempted to address this by determining the prognostic value and potential function of C1ORF112 in low-grade gliomas (LGGs).

Methods: The expression of C1ORF112 in normal and tumor tissues was analyzed using data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Oncomine, and Rembrandt databases. The genetic changes of C1ORF112 in LGG were analyzed using cBioPortal. Survival analysis was used to evaluate the relationship between C1ORF112 expression and survival in patients with LGG. Correlation between immune infiltration and C1ORF112 expression was determined using Timer software. Additionally, data from three online platforms were integrated to identify the co-expressed genes of C1ORF112. The potential biological functions of C1ORF112 were investigated by enrichment analysis.

Results: C1ORF112 mRNA was highly expressed in LGGs (p < 0.01). Area under the ROC curve (AUC) showed that the expression of C1ORF112 in LGG was 0.673 (95% confidence interval [CI] = 0.618–0.728). Kaplan-Meier survival analysis showed that patients with high C1ORF112 expression had lower OS than patients with low C1ORF112 expression (p < 0.05). Multivariate analysis showed that high expression of C1ORF112 was an independent prognostic factor for the overall survival in patients from TCGA and CGGA databases. C1ORF112 expression was positively correlated with six immunoinfiltrating cells (all p < 0.001). The enrichment analysis suggested the enrichment of C1ORF112 and co-expressed genes in cell cycle and DNA replication.

Conclusion: This study suggested that C1ORF112 may be a prognostic biomarker and a potential immunotherapeutic target for LGG.
Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts
Authors: Kleinbrink Erica L. , Gomez-Lopez Nardhy , Ju Donghong , Done Bogdan , Goustin Anton-Scott , Tarca Adi L. , Romero Roberto , Lipovich Leonard
Published: November 2021

In the post-genomic era, our understanding of the molecular regulators of physiologic and pathologic processes in pregnancy is expanding at the whole-genome level. Longitudinal changes in the known protein-coding transcriptome during normal pregnancy, which we recently reported (Gomez-Lopez et al., 2019), have improved our definition of the major operant networks, yet pregnancy-related functions of the non-coding RNA transcriptome remain poorly understood. A key finding of the ENCODE (Encyclopedia of DNA Elements) Consortium, the successor of the Human Genome Project, was that the human genome contains approximately 60,000 genes, the majority of which do not encode proteins. The total transcriptional output of non-protein-coding RNA genes, collectively referred to as the non-coding transcriptome, is comprised mainly of long non-coding RNA (lncRNA) transcripts (Derrien et al., 2012). Although the ncRNA transcriptome eclipses its protein-coding counterpart in abundance, it has until recently lacked a comprehensive, unbiased, genome-scale characterization over the timecourse of normal human pregnancy. Here, we annotated, characterized, and selectively validated the longitudinal changes in the non-coding transcriptome of maternal whole blood during normal pregnancy to term. We identified nine long non-coding RNAs (lncRNAs), including long intergenic non-coding RNAs (lincRNAs) as well as lncRNAs antisense to or otherwise in the immediate vicinity of protein-coding genes, that were differentially expressed with advancing gestation in normal pregnancy: AL355711, BC039551 (expressed mainly in the placenta), JHDM1D-AS1, A2M-AS1, MANEA-AS1, NR_034004, LINC00649, LINC00861, and LINC01094. By cross-referencing our dataset against major public pseudogene catalogs, we also identified six transcribed pseudogenes that were differentially expressed over time during normal pregnancy in maternal blood: UBBP4, FOXO3B, two Makorin (MKRN) pseudogenes (MKRN9P and LOC441455), PSME2P2, and YBX3P1. We also identified three non-coding RNAs belonging to other classes that were modulated during gestation: the microRNA MIR4439, the small nucleolar RNA (snoRNA) SNORD41, and the small Cajal-body specific ncRNA SCARNA2. The expression profiles of most hits were broadly suggestive of functions in pregnancy. These time-dependent changes of the non-coding transcriptome during normal pregnancy, which may confer specific regulatory impacts on their protein-coding gene targets, will facilitate a deeper molecular understanding of pregnancy and lncRNA-mediated molecular pathways at the maternal-fetal interface and of how these pathways impact maternal and fetal health.
Remediation of ABCG5-Linked Macrothrombocytopenia With Ezetimibe Therapy
Authors: Deng Libin , Xu Jingsong , Chen Wei , Guo Shicheng , Steiner Robert D. , Chen Qi , Cheng Zhujun , Xu Yanmei , Yao Bei , Li Xiaoyan , Wang Xiaozhong , Deng Keyu , Schrodi Steven J. , Zhang Dake , Xin Hongbo
Published: November 2021

To investigate refractory hypercholesterolemia, a female patient and relatives were subjected to whole-genome sequencing. The proband was found to have compound heterozygous substitutions p. Arg446Gln and c.1118+3G>T in ABCG5, one of two genes causing sitosterolemia. When tracing these variants in the full pedigree, all maternally related heterozygotes for the intronic ABCG5 variant exhibited large platelets (over 30 fl), which segregated in an autosomal dominant manner, consistent with macrothrombocytopenia, or large platelet syndrome which may be associated with a bleeding tendency. In vitro cell-line and in vivo rat model experiments supported a pathogenic role for the variant and the macrothrombocytopenia was recapitulated in heterozygous rats and human cell lines exhibiting that single variant. Ezetimibe treatment successfully ameliorated all the symptoms of the proband with sitosterolemia and resolved the macrothrombocytopenia of the treated heterozygote relatives. Subsequently, in follow up these observations, platelet size, and size distribution were measured in 1,180 individuals; 30 were found to be clinically abnormal, three of which carried a single known pathogenic ABCG5 variant (p.Arg446Ter) and two individuals carried novel ABCG5 variants of uncertain significance. In this study, we discovered that identification of large platelets and therefore a possible macrothrombocytopenia diagnosis could easily be inadvertently missed in clinical practice due to variable instrument settings. These findings suggest that ABCG5 heterozygosity may cause macrothrombocytopenia, that Ezetimibe treatment may resolve macrothrombocytopenia in such individuals, and that increased attention to platelet size on complete blood counts can aid in the identification of candidates for ABCG5 genetic testing who might benefit from Ezetimibe treatment.
Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Analysis of 35 Cases
Authors: Fang Hongjun , Hu Wenjing , Jiang Zhi , Yang Haiyan , Liao Hongmei , Yang Liming , Wu Liwen
Published: November 2021

Objective

To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children.

Methods

Children hospitalized in the Department of Neurology, Hunan Children’s Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed.

Results

A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff’s brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman’s rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions.

Conclusions

The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.
Fish Paralog Proteins RNASEK-a and -b Enhance Type I Interferon Secretion and Promote Apoptosis
Authors: Sun Zhi-Chao , Jiang Zeyin , Xu Xiaowen , Li Meifeng , Zeng Qing , Zhu Ying , Wang Shanghong , Li Yuanyuan , Tian Xiao-Li , Hu Chengyu
Published: November 2021

Type I interferon and apoptosis elicit multifaceted effects on host defense and various diseases, such as viral infections and cancers. However, the gene/protein network regulating type I interferon and apoptosis has not been elucidated completely. In this study, we selected grass carp (Ctenopharyngodon idella) as an experimental model to investigate the modulation of RNASEK on the secretion of type I interferon and apoptosis. We first cloned two paralogs RNASEK-a and -b in grass carp, defined three exons in each gene, and found the length of both coding regions is 306 bp with 73.27% of protein homology. The protein sequences of the two paralogs are highly conserved across species. Two proteins were mainly localized in early and late endosomes and endoplasmic reticulum. Further, quantitative real-time PCR demonstrated that dsRNA poly I:C and grass carp reovirus upregulated RNASEK-a and -b in grass carp cells and tissues. Overexpression of RNASEK-a and -b individually induced type I interferon expression and the phosphorylation of IRF3/IRF7 shown by Western blot and immunofluorescent staining, increased Bax/Bcl-2 mRNA ratio, DNA fragmentations, TUNEL-positive cells, and the proportion of Annexin V-positive signals in flow cytometry, and activated eIF2α, opposite to that observed when RNASEK-a and -b were knocked down in multiple cell types. Taken together, we claim for the first time that fish paralog proteins RNASEK-a and -b enhance type I interferon secretion and promote apoptosis, which may be involved in the phosphorylation of IRF3/IRF7 and eIF2α, respectively. Our study reveals a previously unrecognized role of RNASEK as a new positive regulator of type I interferon and apoptosis.
Identification and Validation of Immune-Related Gene for Predicting Prognosis and Therapeutic Response in Ovarian Cancer
Authors: Zhang Zhao-Cong , Guo Jun-Nan , Zhang Ning , Wang Zhi-Qiang , Lou Ge , Cui Bin-Bin , Yang Chang
Published: November 2021

Ovarian cancer (OC) is a devastating malignancy with a poor prognosis. The complex tumor immune microenvironment results in only a small number of patients benefiting from immunotherapy. To explore the different factors that lead to immune invasion and determine prognosis and response to immune checkpoint inhibitors (ICIs), we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify key prognostic IRGs. Patients were divided into high-risk and low-risk groups according to their immune and stromal scores. We used a bioinformatics method to identify four key IRGs that had differences in expression between the two groups and affected prognosis. We evaluated the sensitivity of treatment from three aspects, namely chemotherapy, targeted inhibitors (TIs), and immunotherapy, to evaluate the value of prediction models and key prognostic IRGs in the clinical treatment of OC. Univariate and multivariate Cox regression analyses revealed that these four key IRGs were independent prognostic factors of overall survival in OC patients. In the high-risk group comprising four genes, macrophage M0 cells, macrophage M2 cells, and regulatory T cells, observed to be associated with poor overall survival in our study, were higher. The high-risk group had a high immunophenoscore, indicating a better response to ICIs. Taken together, we constructed a PRSM and identified four key prognostic IRGs for predicting survival and response to ICIs. Finally, the expression of these key genes in OC was evaluated using RT-qPCR. Thus, these genes provide a novel predictive biomarker for immunotherapy and immunomodulation.
Tuft Cells Increase Following Ovine Intestinal Parasite Infections and Define Evolutionarily Conserved and Divergent Responses
Authors: Hildersley Katie A. , McNeilly Tom N. , Gillan Victoria , Otto Thomas D. , Löser Stephan , Gerbe François , Jay Philippe , Maizels Rick M. , Devaney Eileen , Britton Collette
Published: November 2021

Helminth parasite infections of humans and livestock are a global health and economic problem. Resistance of helminths to current drug treatment is an increasing problem and alternative control approaches, including vaccines, are needed. Effective vaccine design requires knowledge of host immune mechanisms and how these are stimulated. Mouse models of helminth infection indicate that tuft cells, an unusual type of epithelial cell, may ‘sense’ infection in the small intestine and trigger a type 2 immune response. Currently nothing is known of tuft cells in immunity in other host species and in other compartments of the gastrointestinal (GI) tract. Here we address this gap and use immunohistochemistry and single cell RNA-sequencing to detail the presence and gene expression profile of tuft cells in sheep following nematode infections. We identify and characterize tuft cells in the ovine abomasum (true stomach of ruminants) and show that they increase significantly in number following infection with the globally important nematodes Teladorsagia circumcincta and Haemonchus contortus. Ovine abomasal tuft cells show enriched expression of tuft cell markers POU2F3, GFI1B, TRPM5 and genes involved in signaling and inflammatory pathways. However succinate receptor SUCNR1 and free fatty acid receptor FFAR3, proposed as ‘sensing’ receptors in murine tuft cells, are not expressed, and instead ovine tuft cells are enriched for taste receptor TAS2R16 and mechanosensory receptor ADGRG6. We also identify tuft cell sub-clusters at potentially different stages of maturation, suggesting a dynamic process not apparent from mouse models of infection. Our findings reveal a tuft cell response to economically important parasite infections and show that while tuft cell effector functions have been retained during mammalian evolution, receptor specificity has diverged. Our data advance knowledge of host-parasite interactions in the GI mucosa and identify receptors that may potentiate type 2 immunity for optimized control of parasitic nematodes.
Identification and Validation of 17-lncRNA Related to Regulatory T Cell Heterogeneity as a Prognostic Signature for Head and Neck Squamous Cell Carcinoma
Authors: Sun Qi , Li Yumei , Yang Xin , Wu Xinxin , Liu Zhen , Mou Yakui , Song Xicheng
Published: November 2021

Successful eradication of tumors by the immune system depends on generation of antigen-specific T cells that migrate to tumor sites and kill cancerous cells. However, presence of suppressive Treg populations inside tumor microenvironment hinders effector T cell function and decreases antitumor immunity. In this study we independently evaluated and confirmed prognostic signature of 17-Treg-related-lncRNA. Immune cell infiltration analysis using 17-lncRNA signature as a probe, accurately described Treg populations in tumor immune microenvironment. 17-lncRNA signature model predicted prognosis with excellent accuracy in all three cohorts: training cohort (AUC=0.82), testing cohort (AUC=0.61) and total cohort (AUC=0.72). The Kaplan-Meier analysis confirmed that the overall survival of patients in the low-risk group was significantly better than those in the high-risk group(P<0.001). CIBERSORT analysis confirmed that low risk group had higher infiltration of tumor killer CD8 T cells, memory activated CD4 T cells, follicular helper T cells and T cells regulatory (Tregs), and lower expression of M0 macrophages and Mast cells activated. These results indicate that the 17-lncRNA signature is a novel prognostic and support the use of lncRNA as a stratification tool to help guide the course of treatment and clinical decision making in patients at high risk of HNSCC.
Comparing the Expressions of Vitamin D Receptor, Cell Proliferation, and Apoptosis in Gastric Mucosa With Gastritis, Intestinal Metaplasia, or Adenocarcinoma Change
Authors: Chen Li-Wei , Chang Liang-Che , Hua Chung-Ching , Cheng Tzu-Chien , Lee Chin-Chan
Published: November 2021

Background: This study aimed to compare the expression of vitamin D receptor (VDR), cell proliferation, and apoptosis in the gastric mucosa of patients with gastritis, intestinal metaplasia (IM), and adenocarcinoma using artificial intelligence.

Material and Methods: This study retrospectively enrolled patients at the Keelung Chang Gung Memorial Hospital from November of 2016 to June, 2017, who were diagnosed with gastric adenocarcinoma. The inclusion criteria were patients' pathologic reports that revealed all compartments of Helicobacter pylori infection, gastritis, IM, and adenocarcinoma simultaneously in the same gastric sample. Tissue slides after immunohistochemical (IHC) staining were transformed into digital images using a scanner and counted using computer software (QuPath and ImageJ). IHC staining included PA1-711 antibody for VDR, Ki67 antigen for proliferation, and M30 antibody CK18 for apoptosis.

Results: Twenty-nine patients were included in the IHC staining quantitative analysis. The mean age was 69.1 ± 11.3 y/o. Most (25/29, 86.2%) patients had poorly differentiated adenocarcinoma. The mean expression of Ki67 and CK18 increased progressively from gastritis and IM to adenocarcinoma, with statistical significance (P < 0.05). VDR expression did not correlate with Ki67 or CK18 expression. Survival time was only correlated with tumor stage (correlation coefficient = −0.423, P value < 0.05), but was not correlated with the expression of VDR, Ki67, and CK18.

Conclusion: Ki67 expression and CK18 expression progressively increased in the areas of gastritis, IM, and adenocarcinoma. No correlation between VDR expression and Ki67 or CK18 expression was found in this study.
ASHA-Led Community-Based Groups to Support Control of Hypertension in Rural India Are Feasible and Potentially Scalable
Authors: Riddell Michaela A. , Mini G. K. , Joshi Rohina , Thrift Amanda G. , Guggilla Rama K. , Evans Roger G. , Thankappan Kavumpurathu R. , Chalmers Kate , Chow Clara K. , Mahal Ajay S. , Kalyanram Kartik , Kartik Kamakshi , Suresh Oduru , Thomas Nihal , Maulik Pallab K. , Srikanth Velandai K. , Arabshahi Simin , Varma Ravi P. , D'Esposito Fabrizio , Oldenburg Brian
Published: November 2021

Background: To improve the control of hypertension in low- and middle-income countries, we trialed a community-based group program co-designed with local policy makers to fit within the framework of India's health system. Trained accredited social health activists (ASHAs), delivered the program, in three economically and developmentally diverse settings in rural India. We evaluated the program's implementation and scalability.

Methods: Our mixed methods process evaluation was guided by the United Kingdom Medical Research Council guidelines for complex interventions. Meeting attendance reports, as well as blood pressure and weight measures of attendees and adherence to meeting content and use of meeting tools were used to evaluate the implementation process. Thematic analysis of separate focus group discussions with participants and ASHAs as well as meeting reports and participant evaluation were used to investigate the mechanisms of impact.

Results: Fifteen ASHAs led 32 community-based groups in three rural settings in the states of Kerala and Andhra Pradesh, Southern India. Overall, the fidelity of intervention delivery was high. Six meetings were delivered over a 3-month period to each of the intervention groups. The mean number of meetings attended by participants at each site varied significantly, with participants in Rishi Valley attending fewer meetings [mean (SD) = 2.83 (1.68)] than participants in West Godavari (Tukeys test, p = 0.009) and Trivandrum (Tukeys test, p < 0.001) and participants in West Godavari [mean (SD) = 3.48 (1.72)] attending significantly fewer meetings than participants in Trivandrum [mean (SD) = 4.29 (1.76), Tukeys test, p < 0.001]. Culturally appropriate intervention resources and the training of ASHAs, and supportive supervision of them during the program were critical enablers to program implementation. Although highly motivated during the implementation of the program ASHA reported historical issues with timely remuneration and lack of supportive supervision.

Conclusions: Culturally appropriate community-based group programs run by trained and supported ASHAs are a successful and potentially scalable model for improving the control of hypertension in rural India. However, consideration of issues related to unreliable/insufficient remuneration for ASHAs, supportive supervision and their formal role in the wider health workforce in India will be important to address in future program scale up.

Trial Registration: Clinical Trial Registry of India [CTRI/2016/02/006678, Registered prospectively].
Achieving WHO's Goal for Reducing Cesarean Section Rate in a Chinese Hospital
Authors: Ji Yan-Jie , Wang Hai-Bo , Bai Zhi , Long Da-Jian , Ma Kaidong , Yan Jie , Li Yun-Xiu , Wu Yang-Feng , Yang Huixia
Published: November 2021

Background: To address the worldwide dramatically increased Cesarean section (CS) rate in the past decades, WHO has recommended the CS rate should not be higher than 10–15%. Whether it is achievable remains unknown.

Methods: We collected the data of delivery from 2008 to 2017 in two typical regional hospitals in China: Longhua Hospital (national policies rigorously implemented) and Dongguan Hospital (national policies not rigorously implemented). We compared between the two hospitals the 10 years trend in annual rate of CS, standardized by age, education level, parity, and CS history, against the time of issuing relevant national, local, and hospital policies.

Results: In 10 years, 42,441 women in Longhua and 36,935 women in Dongguan have given birth. China's first national policy on CS reduction was issued in 2010 and the formal relaxation of one-child policy was issued in 2015–2016. In Longhua, the standardized annual CS rate was around 35% in 2008–2009, which declined sharply since 2010 down to 13.1% in 2016 (p < 0.001) and then leveled off. In contrast, in Dongguan, the rate stayed around 25% at the beginning, increased to 36% in 2011, decreased sharply to 27% in 2012, and leveled off until 2015 (p < 0.001), and then bounced back to 35% in 2017. The proportion of women with the history of CS increased significantly in the two hospitals (both roughly from 6% before 2010 to 20% after 2015). Analyses stratified by modified Robson classification showed that CS rates reduced in all risk classes of delivery women in Longhua but only in the Robson class 2 group in Dongguan. Major complications did not differ by hospital.

Conclusion: With vigorously implementing national policies at micro levels, the WHO-recommended CS rate could be achieved without increase in major complications.
Patients With IBD Receiving Methotrexate Are at Higher Risk of Liver Injury Compared With Patients With Non-IBD Diseases: A Meta-Analysis and Systematic Review
Authors: Wang Yang , Li Yimin , Liu Yun , Zhang Yifan , Ke Ziliang , Zhang Yu , Liu Yulan
Published: November 2021

Background: Methotrexate is well-known in treating inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis (Ps), and psoriatic arthritis (PsA). Several reports have indicated a higher incidence of methotrexate (MTX)-related liver adverse events in patients with IBD. We aim to investigate the risk of liver injury in patients with IBD and those with non-IBD diseases treated with MTX.

Methods: We searched PubMed, Embase, and the Cochrane Library for articles that reported liver adverse events in patients with IBD, RA, and Ps/PsA, receiving MTX therapy. Additional articles were obtained by screening the references of recent meta-analysis and reviews. Raw data from included articles were pooled to calculate the cumulative incidence of total liver injury (TLI), MTX discontinuation (MTX-D), and liver fibrosis (LF). RR (relative risk) was calculated to compare the difference between patients with IBD and those with non-IBD diseases.

Results: A total of 326 articles with 128,876 patients were included. The patients with IBD had higher incidence of TLI [11.2 vs. 9.2%; relative risk (RR) = 1.22; P = 0.224] and MTX-D (2.6 vs. 1.8%; RR, 1.48; P = 0.089) than patients with non-IBD diseases. Due to the publication bias, trim-and-fill was performed. Afterwards, the patients with IBD showed significantly higher risk of TLI (11.2 vs. 3%; RR = 3.76; p < 0.001), MTX-D (3.3 vs. 0.7%; RR = 5; p < 0.001) and LF (3.1 vs. 0.1%; RR = 38.62; P = 0.001) compared with patients with non-IBD diseases.

Conclusion: IBD is associated with a higher risk of MTX-related liver injury. The mechanism of MTX-induced hepatotoxicity might be different in IBD and non-IBD diseases, and needs to be verified in future research.
Radiological Characteristics of Patients With Anti-MDA5–Antibody-Positive Dermatomyositis in 18F-FDG PET/CT: A Pilot Study
Authors: Cao Heng , Liang Junyu , Xu Danyi , Liu Yinuo , Yao Yinan , Sun Yiduo , He Ye , Lin Jin
Published: November 2021

Objective: To elucidate the 18F-fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in the patients with anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM).

Methods: This retrospective cross-sectional study included 26 patients with anti-MDA5+ DM and 43 patients with anti-MDA5 negative (anti-MDA5–) idiopathic inflammatory myopathy (IIM) who were examined by 18F-FDG PET/CT from January 1, 2017 to December 31, 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of the patients were measured and analyzed.

Results: Compared with the anti-MDA5– group, the patients in the anti-MDA5+ group showed higher bilateral lung SUVmax (p = 0.029), higher SUVmax of spleen (p = 0.011), and bone marrow (p = 0.048). Significant correlations between the spleen SUVmax and serum ferritin levels (r = 0.398, p < 0.001), erythrocyte sedimentation rate (ESR) (r = 0.274, p = 0.023), platelet count (r = −0.265, p= 0.028), myositis disease activity assessment score (r = 0.332, p = 0.005), bone marrow SUVmax (r = 0.564, p < 0.001), and bilateral lung SUVmax (r = 0.393, p < 0.001) were observed.

Conclusion:18F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in the patients with anti-MDA5+ DM.
Dysregulated Serum Lipid Metabolism Promotes the Occurrence and Development of Diabetic Retinopathy Associated With Upregulated Circulating Levels of VEGF-A, VEGF-D, and PlGF
Authors: Zhang Xinyuan , Qiu Bingjie , Wang Qiyun , Sivaprasad Sobha , Wang Yanhong , Zhao Lin , Xie Rui , Li Lei , Kang Wenting
Published: November 2021

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR.

Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C).

Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = −2.61, P = 0.009) and AI (Z = −2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49].

Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.
Current Practice of Imaging-Guided Interventional Procedures in Rheumatic and Musculoskeletal Diseases: Results of a Multinational Multidisciplinary Survey
Authors: Carubbi Francesco , Bosch Philipp , Machado Pedro M. , Scirè Carlo Alberto , Alunno Alessia , Proft Fabian , Baraliakos Xenofon , Dejaco Christian
Published: November 2021

Objectives: To investigate opinion and routine practice of specialists from different disciplines on imaging techniques for interventional procedures related to rheumatic and musculoskeletal diseases (RMDs).

Methods: An English-language questionnaire was developed by an international working group and distributed to health care providers of various disciplines involved in the care of people with RMDs via an online survey tool (SoSci Survey®) from December 2019 to May 2020.

Results: A total of 1,105 respondents from 56 countries completed the survey, over 60% of participants were rheumatologists. The majority of respondents (88%) performed interventional procedures in RMDs patients and 90% of them used imaging guidance. Ultrasonography was the most frequently used technique, particularly among rheumatologists. X-ray and computed tomography were mainly used by radiologists. A discrepancy emerged between the importance assigned to certain items such as the availability of a second operator and their actual implementation in clinical practice. Local barriers, lack of resources and facilities were mentioned as the most relevant obstacles in this regard. Lack of training on imaging and/or imaging guided procedures did not emerge as a barrier to perform such interventions; in fact, 19% of respondents performing the procedures indicated not to have received adequate training in this field.

Conclusions: This is the first multinational multidisciplinary survey exploring in detail the opinions and practice on imaging guidance for interventional procedures in RMDs. A harmonization of protocols based on international guidelines, along with adequate training programmes and interventions on barriers at national/local levels are the main unmet needs requiring attention.
Local Delivery and Glioblastoma: Why Not Combining Sustained Release and Targeting?
Authors: Gazaille Claire , Sicot Marion , Saulnier Patrick , Eyer Joël , Bastiat Guillaume
Published: November 2021

Glioblastoma is one of the most aggressive brain tumors and is associated with a very low overall median survival despite the current treatment. The standard of care used in clinic is the Stupp's protocol which consists of a maximal resection of the tumor when possible, followed by radio and chemotherapy using temozolomide. However, in most cases, glioblastoma cells infiltrate healthy tissues and lead to fatal recurrences. There are a lot of hurdles to overcome in the development of new therapeutic strategies such as tumor heterogeneity, cell infiltration, alkylating agent resistance, physiological barriers, etc., and few treatments are on the market today. One of them is particularly appealing because it is a local therapy, which does not bring additional invasiveness since tumor resection is included in the gold standard treatment. They are implants: the Gliadel® wafers, which are deposited post-surgery. Nevertheless, in addition to presenting important undesirable effects, it does not bring any major benefit in the therapy despite the strategy being particularly attractive. The purpose of this review is to provide an overview of recent advances in the development of innovative therapeutic strategies for glioblastoma using an implant-type approach. The combination of this local strategy with effective targeting of the tumor microenvironment as a whole, also developed in this review, may be of interest to alleviate some of the obstacles encountered in the treatment of glioblastoma.
Capsular Genotype and Lipooligosaccharide Class Associated Genomic Characterizations of Campylobacter jejuni Isolates From Food Animals in China
Authors: Zang Xiaoqi , Lv Hongyue , Tang Haiyan , Jiao Xinan , Huang Jinlin
Published: November 2021

Campylobacter jejuni (C. jejuni) is the leading causative agent of gastroenteritis and Guillain–Barré syndrome (GBS). Capsular polysaccharide (CPS) and lipooligosaccharide (LOS) contribute to the susceptibility of campylobacteriosis, which have been concern the major evaluation indicators of C. jejuni isolates from clinical patients. As a foodborne disease, food animal plays a primary role in the infection of campylobacteriosis. To assess the pathogenic characterizations of C. jejuni isolates from various ecological origins, 1609 isolates sampled from 2005 to 2019 in China were analyzed using capsular genotyping. Strains from cattle and poultry were further characterized by LOS classification and multilocus sequence typing (MLST), compared with the isolates from human patients worldwide with enteritis and GBS. Results showed that the disease associated capsular genotypes and LOS classes over-represented in human isolates were also dominant in animal isolates, especially cattle isolates. Based on the same disease associated capsular genotype, more LOS class types were represented by food animal isolates than human disease isolates. Importantly, high-risk lineages CC-22, CC-464, and CC-21 were found dominated in human isolates with GBS worldwide, which were also represented in the food animal isolates with disease associated capsular types, suggesting a possibility of clonal spread of isolates across different regions and hosts. This is the first study providing genetic evidence for food animal isolates of particular capsular genotypes harbor similar pathogenic characteristics to human clinical isolates. Collective efforts for campylobacteriosis hazard control need to be focused on the zoonotic pathogenicity of animal isolates, along the food chain “from farm to table.”