bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent trends of ecosystem status and services in the Hexi Corridor
Authors: Zhu Hanshou , Zhai Jun , Hou Peng , Gao Haifeng , He Yingli , Jin Diandian , Xu Ningning 
Published: September 2022

In terms of ecosystem structure, quality, and service, we have constructed a total of 18 characteristic evaluation indicators that could reflect the “state change interaction” of the ecosystem and analyzed the Spatio-temporal change of the ecosystem in Hexi Corridor from 2000 to 2020. The results show that: 1. The improvement of ecosystem and service is more obvious in the areas with a better ecological background in the East. The supply and regulation services of the ecosystem are synergetic. 2. In the past 2 decades, the ecological conditions of the Hexi corridor have improved as a whole, and the hot spots for improving ecosystem quality and services have gradually moved eastward. 3. Ecosystem changes have significantly changed the quantity and relationship of ecosystem services, showing strong spatial heterogeneity. For example, the loss of natural vegetation in the central and eastern regions with good ecological backgrounds has improved the water conservation service and also enhanced the synergy between it and the supply service. From the perspective of the relationship between ecosystem regulation services and supply services, the coordination characteristics are weakened, but the performance of regions with a poor ecological background in the west is just the opposite. In short, the typical climate characteristics of dry land with little rain and the spatial pattern of water resource shortage not only jointly determine the ecosystem background of the region, but also bring significant spatial differences and greater uncertainties to the relationship between ecosystem transformation and ecosystem services. Therefore, dryland ecosystem management and protection should be based on detailed and differentiated ecosystem assessment, taking into account regional natural resource endowment, giving priority to improving the stability of the regional ecosystem and gradually increasing regional ecosystem services.
The effects of park and sea landscape on property value in a tourist city
Authors: Shi Dequn , Zhang Yuhui , Liang Zengxian 
Published: September 2022

Theorists have traditionally considered the effects of single rather than multiple landscape attributes on property prices, and ignored the interaction between landscape-specific housing attributes. The aim of this paper is to analyze the hedonic attributes of property prices and compare the effects on property prices of two key landscape attributes. Seventeen hedonic attributes are used to build a hedonic-pricing model with five dimensions: structure, neighborhood and community, location, environment, and time. A sample of 688 valid houses within 1,000 m of Xiangshan Park in the city of Zhuhai, China is collected. The selected hedonic attributes are found to have significant effects on property prices, explaining around 91% of the observed variation in price. Proximity to the sea has a greater positive influence on property prices than proximity to parks. In addition, people prefer to buy properties with sea views than to live close to the sea.
MicroRNAs as diagnostic biomarkers for Tuberculosis: A systematic review and meta- analysis
Authors: Daniel Evangeline Ann , Sathiyamani Balakumaran , Thiruvengadam Kannan , Vivekanandan Sandhya , Vembuli Hemanathan , Hanna Luke Elizabeth 
Published: September 2022

BackgroundThe early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to Mycobacterium tuberculosis (Mtb).MethodsPubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.ResultsWe retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.ConclusionmiRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance. Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).
Identification of four immune subtypes in locally advanced rectal cancer treated with neoadjuvant chemotherapy for predicting the efficacy of subsequent immune checkpoint blockade
Authors: He Le , Jin Min , Jian Dan , Yang Bo , Dai Nan , Feng Yan , Xiao He , Wang Dong 
Published: September 2022

IntroductionNeoadjuvant chemoradiotherapy (nCRT) is the foundation treatment for locally advanced rectal cancer (LARC). The nCRT can improve the efficacy of immunotherapy because of its in situ vaccine effect.ObjectiveThe aim is to identify stable and reliable transcriptome signatures to predict the efficacy of immune checkpoint blockade (ICB) in patients with LARC.MethodsImmunophenotyping was established using xCell immune cell infiltration abundance and consistent clustering in GSE39582 and verified in several data sets. The effects of immunophenotyping, follicular regulatory T cells, tumor-associated fibroblasts (CAFs), and tertiary lymphoid structure (TLS) signatures on the efficacy of ICB were analyzed using IMvigor210, GSE91061, and an independent Daping Hospital (DPH) cohort.ResultsThere are four stable and repeatable immune subtypes in rectal cancer, among which C1 is a low immune infiltration type, C2 is a high interstitial infiltration type, C3 is a high immune infiltration type, and C4 is an ion channel type. C2 is mainly characterized by high infiltration of CAF. C3 is characterized by high infiltration of cytotoxic T lymphocytes, high expression of PD-L1 and TLS. In rectal cancer patients receiving nCRT, immunophenotyping was not significantly associated with pathological remission rate, but immunophenotyping was an independent prognostic factor of RFS. In IMvigor210 patients treated with atezolizumab, the pathological remission rates of C1, C2, C3, and C4 were 23.86%, 10.94%, 33.33%, and 23.08% respectively (χ2 = 8.981, P = 0.029), which were 11.76%, 50.00%, 42.86%, and 0.0% respectively in the GSE91061 patient treatment with nivolumab (Fisher’s exact probability, P = 0.018). Both follicular regulatory T cells and CAF showed a further impact on the ICB therapeutic efficacy of C2 and C3 subtypes. Additionally, both the GSE91404 and DPH cohorts showed that nCRT treatment induced a significant increase in the expression of TNFRSF9 and the abundance of macrophages in the C3 subtype.ConclusionOur data suggest that there are four immune types of rectal cancer, which are related to the prognosis of patients. Among them, C3 and some C2 subtypes represent the patients who may benefit from ICB after nCRT treatment.
Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy
Authors: Zhou Shujie , Ren Fei , Meng Xiangjiao 
Published: September 2022

BackgroundFew treatment options are available for brain metastases (BMs) in EGFR-mutant non-small cell lung cancer (NSCLC) that progress with prior EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. This study aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) therapy in these patients.MethodsNSCLC patients with confirmed sensitive EGFR mutations and BMs were retrospectively reviewed. All patients experienced failure of EGFR-TKI therapy and were divided into two cohorts based on subsequent treatment. Cohort 1 included patients who received ICI therapy, while cohort 2 included patients treated with chemotherapy. Overall and intracranial objective response rates (ORRs) were used to evaluate the treatment response. Overall and intacranial progression-free survival (PFS) were calculated by Kaplan−Meier analysis and compared with the log-rank test. Univariate and multivariate Cox analyses were used to identify prognostic factors.ResultsA total of 53 patients treated with ICI therapy and 40 patients treated with chemotherapy were included in cohorts 1 and 2, respectively. In cohort 1, the overall ORR was 20.8%, with a median overall PFS of 4.2 months. The median intracranial PFS was 5.1 months. Of the 38 patients with measurable intracranial lesions, the intracranial ORR was 21.0%. Patients who received ICI combined with chemotherapy had the highest intracranial ORR of 37.5%. Compared to patients treated with chemotherapy in cohort 2, patients receiving ICI combined with chemotherapy had both longer intracranial PFS (6.4 vs. 5.1 months, p = 0.110) and overall PFS (6.2 vs. 4.6 months, p = 0.054), and these differences approached statistical significance. Univariate and multivariate Cox analyses demonstrated that high disease burden (p = 0.019), prior third-generation EGFR-TKI therapy (p = 0.019), and a poor lung immune prognostic index (LIPI) (p = 0.012) were independent negative predicators of overall PFS and that multiple BMs were negatively correlated with intracranial PFS among patients treated with ICI therapy.ConclusionsOur results suggested that ICI combined with chemotherapy had potent intracranial efficacy and may be a promising treatment candidate in EGFR-mutant NSCLC patients with BMs for whom prior EGFR-TKI therapy failed.
Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility
Authors: Lopez-Rivera Daniela Olivia , Castano-Jaramillo Lina Maria , Yamazaki-Nakashimada Marco Antonio , Ramirez Uribe Rosa María Nideshda , Corcuera Delgado Celso Tomás , Ignorosa-Arellano Karen R. , Medina-Torres Edgar Alejandro , Berrón Ruiz Laura , Espinosa-Padilla Sara Elva , Scheffler-Mendoza Selma C. , López-Velázquez Gabriel , Cruz-Munoz Mario Ernesto , Lugo Reyes Saul O. 
Published: September 2022

IntroductionThe transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals.ObjectiveWe aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology.MethodsAfter informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells.ResultsWe describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis.DiscussionNFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.
Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD
Authors: Wang Di , Chen Bingnan , Bai Shuang , Zhao Li 
Published: September 2022

ObjectiveTo study the tissue-infiltrating immune cells of the emphysema phenotype of chronic obstructive pulmonary disease (COPD) and find the molecular mechanism related to the development of emphysema to offer potential targets for more precise treatment of patients with COPD.MethodsCombined analyses of COPD emphysema phenotype lung tissue-related datasets, GSE47460 and GSE1122, were performed. CIBERSORT was used to assess the distribution of tissue-infiltrating immune cells. Weighted gene co-expression network analysis (WGCNA) was used to select immune key genes closely related to clinical features. Rt-qPCR experiments were used for the validation of key genes. Emphysema risk prediction models were constructed by logistic regression analysis and a nomogram was developed.ResultsIn this study, three immune cells significantly associated with clinical features of emphysema (FEV1 post-bronchodilator % predicted, GOLD Stage, and DLCO) were found. The proportion of neutrophils (p=0.025) infiltrating in the emphysema phenotype was significantly increased compared with the non-emphysema phenotype, while the proportions of M2 macrophages (p=0.004) and resting mast cells (p=0.01) were significantly decreased. Five immune-related differentially expressed genes (DEGs) were found. WGCNA and clinical lung tissue validation of patients with emphysema phenotype were performed to further screen immune-related genes closely related to clinical features. A key gene (SERPINA3) was selected and included in the emphysema risk prediction model. Compared with the traditional clinical prediction model (AUC=0.923), the combined prediction model, including SERPINA3 and resting mast cells (AUC=0.941), had better discrimination power and higher net benefit.ConclusionThis study comprehensively analyzed the tissue-infiltrating immune cells significantly associated with emphysema phenotype, including M2 macrophages, neutrophils, and resting mast cells, and identified SERPINA3 as a key immune-related gene.
Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility
Authors: Roy Neelanjana , Nadda Neeti , Kumar Hem , Prasad Chandreswar , Kumar Jha Jyotish , Pandey Hem Chandra , Vanamail Perumal , Saraya Anoop , Balhara Yatan Pal Singh , Shalimar  , Nayak Baibaswata 
Published: September 2022

BackgroundAlcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD.MethodsPatients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined.ResultsThe CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression.ConclusionEnhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.
Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma
Authors: Tsao Chin-Ho , Jhou Rong-Hong , Ke Chien-Chih , Chang Chun-Wei , Chang Chi-Wei , Yang Bang-Hung , Huang Wen-Sheng , Shih Bing-Fu , Liu Ren-Shyan 
Published: September 2022

BackgroundDe novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy.MethodsWe investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice.ResultsDual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat.ConclusionThe proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.
Efficacy of obstructive sleep apnea treatment by antileukotriene receptor and surgery therapy in children with adenotonsillar hypertrophy: A descriptive and cohort study
Authors: Tran-Minh Dien , Phi-Thi-Quynh Anh , Nguyen-Dinh Phuc , Duong-Quy Sy 
Published: September 2022

BackgroundPrevalence of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy is high and related to the occlusion of the upper airway. The main treatments of OSA in these children is adenotonsillectomy. However, this intervention is an invasive method with a various success rate. Thus, the indications of tonsillectomy remain debatable and non-invasive treatment is still a potential choice in these patients.MethodsIt was a cross-sectional and interventional study. This study included children aged from 2 to 12 years-old who were diagnosed with OSA by respiratory polygraphy and had tonsillar hypertrophy with/without adenoid hypertrophy. All main data including age, gender, height, weight, body mass index (BMI), clinical symptoms, and medical history were recorded for analysis. Physical examination and endoscopy were done to evaluate the size of tonsillar and adenoid hypertrophy by using Brodsky and Likert classifications, respectively. The severity of OSA was done by using the classification of AHI severity for children.ResultsThere were 114 patients (2–12 years old) with a mean age of 5.5 ± 2.1 years included in the present study. The main reasons for consultations were snoring (96.7%), a pause of breathing (57.1%), an effort to breathe (36.8%), unrefreshing sleep (32%), doziness (28.2%), and hyperactivity (26.3%). There were 36% of subjects with tonsillar hypertrophy grade 1–2, 48.2% with grade 3, and 15.8% with grade 4 (Brodsky classification); among them, there were 46.5% of subjects with grades 1–2 of adenoid hypertrophy, 45.6% with grade 3, and 7.0% with grade 4 (Likert classification). The mean AHI was 12.6 ± 11.2 event/h. There was a significant correlation between the mean AHI and the level of tonsillar and adenoid hypertrophy severity (r = 0.7601 and r = 0.7903; p &lt; 0.05 and p &lt; 0.05, respectively). The improvement of clinical symptoms of study subjects was found in both groups treated with ALR (antileukotriene receptor) or ST (surgery therapy). The symptoms related to OSA at night including snoring, struggle to breathe, sleeping with the mouth open, and stopping breathing during sleep were significantly improved after treatment with ATR and with ST (p &lt; 0.001 and p = 0.001, respectively). The mean AHI was significantly reduced in comparison with before treatment in study subjects treated with ALR (0.9 ± 1.0 vs. 3.9 ± 2.7 events/h; p = 0.001) or with ST (3.5 ± 1.4 vs. 23.4 ± 13.1 events/h; p &lt; 0.001).ConclusionThe treatment of OSA due to adeno-tonsillar hypertrophy with ALR for moderate OSA or surgery for severe OSA might reduce the symptoms related to OSA at night and during the day.