bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of land fragmentation on farmers’ rotation behavior in rural China
Authors: Yang Boqiong , Duan Yuxin , Zhao Qiran 
Published: October 2022

Background: Arable land protection is the key to guaranteeing food security in China, as well as protecting the ecological environment and ensuring the continuous increase of farmers’ income. Crop rotation is one of the many forms of arable land protection.Objectives: In this paper, we aim to estimate the possible influence of land fragmentation, famers’ willingness to rotate, and farmers’ rotation behavior in China. Combining farmers’ willingness to rotate and farmers’ rotation behavior using the theory of intermediary effect, we determine whether the degree of land fragmentation will affect farmers’ willingness to rotate or not, thereby affecting farmers’ rotation behavior.Methodology: This study based on the field survey conducted in Heilongjiang Province in 2018, focused on the impact of land fragmentation on farmers’ rotation behavior through OLS and Probit model. Specifically, the degree of land fragmentation and farmers’ willingness to rotate are 0.187 and 0.463, respectively. Further, by taking the farmers’ willingness to rotate as the mediator, this paper discusses the mechanism on the effect of land fragmentation on farmers’ rotation behavior. Finally, the farmers are divided into large and small farmers—according to acreage for heterogeneity analysis.Main findings: This study found that the degree of land fragmentation affects farmers’ willingness to rotate, thereby having some mediating effects on farmers’ rotation behavior.Conclusion: The indirect impact accounts for only 39.86% of the total impact, and more comes from the direct impact. Thus, policy makers should strengthen the guidance for farmers to stimulate their behavior and willingness to implement rotation. Furthermore, it is vital to improve the popularization of arable land protection knowledge and increase crop rotation subsidies.
Genotypic spectrum underlying tetrahydrobiopterin metabolism defects: Experience in a single Mexican reference center
Authors: Vela-Amieva M. , Alcántara-Ortigoza M. A. , Ibarra-González I. , González-del Angel A. , Fernández-Hernández L. , Guillén-López S. , López-Mejía L. , Carrillo-Nieto R. I. , Fiesco-Roa M. O. , Fernández-Lainez C. 
Published: October 2022

Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D.Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico.Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling.Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G&gt;T or p.(?), c.214G&gt;T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic.Conclusion: A higher proportion of BH4D (9.8 vs. 1%–2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.
Immune-infiltrating signature-based classification reveals CD103+CD39+ T cells associate with colorectal cancer prognosis and response to immunotherapy
Authors: Luo Yang , Zong Yunfeng , Hua Hanju , Gong Meiting , Peng Qiao , Li Chen , Neculai Dante , Zeng Xun 
Published: October 2022

BackgroundCurrent stratification systems for tumor prognostic prediction and immunotherapeutic efficacy evaluation are less satisfying in colorectal cancer (CRC). As infiltrating immune cells in tumor microenvironment (TME) played a key role in tumor progression and responses to immune checkpoint blockade (ICB) therapy, we want to construct an immune-related scoring system with detailed immune profiles to stratify CRC patients.MethodsWe developed a scoring system based on immune-related signatures and validated its ability to predict prognosis and immunotherapeutic outcomes in CRC. CD45+ cells from CRC patients were sorted to investigate detailed immune profiles of the stratification system using mass cytometry. A single-cell RNA sequencing dataset was used to analyze transcriptomic profiles.ResultsWe constructed an immune-related signature score (IRScore) based on 54 recurrence-free survival (RFS)-related immune signatures to stratify CRC patients. We revealed that IRScore was positively correlated with RFS and favorable outcomes in ICB treatment. Moreover, we depicted a detailed immune profile in TME using mass cytometry and identified that CD103+CD39+ T cells, characterized by an exhaustive, cytotoxic and proliferative phenotype, were enriched in CRC patients with high IRScore. As a beneficial immune signature, CD103+CD39+ T cells could predict prognosis and responses to ICB therapy in CRC.ConclusionsAll the analyses above revealed that IRScore could be a valuable tool for predicting prognosis and facilitating the development of new therapeutic strategies in CRC, and CD103+CD39+ T cells were one of defined immune signatures in IRScore, which might be a key factor for antitumor immunity.
SARS-CoV-2 specific antibody trajectories in mothers and infants over two months following maternal infection
Authors: Martin Melanie A. , Keith Monica , Pace Ryan M. , Williams Janet E. , Ley Sylvia H. , Barbosa-Leiker Celestina , Caffé Beatrice , Smith Caroline B. , Kunkle Amanda , Lackey Kimberly A. , Navarrete Alexandra D. , Pace Christina D. W. , Gogel Alexandra C. , Eisenberg Dan T.A. , Fehrenkamp Bethaney D. , McGuire Mark A. , McGuire Michelle K. , Meehan Courtney L. , Brindle Eleanor 
Published: October 2022

Infants exposed to caregivers infected with SARS-CoV-2 may have heightened infection risks relative to older children due to their more intensive care and feeding needs. However, there has been limited research on COVID-19 outcomes in exposed infants beyond the neonatal period. Between June 2020 – March 2021, we conducted interviews and collected capillary dried blood spots from 46 SARS-CoV-2 infected mothers and their infants (aged 1-36 months) for up to two months following maternal infection onset (COVID+ group, 87% breastfeeding). Comparative data were also collected from 26 breastfeeding mothers with no known SARS-CoV-2 infection or exposures (breastfeeding control group), and 11 mothers who tested SARS-CoV-2 negative after experiencing symptoms or close contact exposure (COVID- group, 73% breastfeeding). Dried blood spots were assayed for anti-SARS-CoV-2 S-RBD IgG and IgA positivity and anti-SARS-CoV-2 S1 + S2 IgG concentrations. Within the COVID+ group, the mean probability of seropositivity among infant samples was lower than that of corresponding maternal samples (0.54 and 0.87, respectively, for IgG; 0.33 and 0.85, respectively, for IgA), with likelihood of infant infection positively associated with the number of maternal symptoms and other household infections reported. COVID+ mothers reported a lower incidence of COVID-19 symptoms among their infants as compared to themselves and other household adults, and infants had similar PCR positivity rates as other household children. No samples returned by COVID- mothers or their infants tested antibody positive. Among the breastfeeding control group, 44% of mothers but none of their infants tested antibody positive in at least one sample. Results support previous research demonstrating minimal risks to infants following maternal COVID-19 infection, including for breastfeeding infants.
Identification of hub genes and their correlation with infiltration of immune cells in MYCN positive neuroblastoma based on WGCNA and LASSO algorithm
Authors: Chen Ji , Sun Mengjiao , Chen Chuqin , Jiang Bin , Fang Yongjun 
Published: October 2022

BackgroundThe prognosis of MYCN positive NB is poor, and there is no targeted drug for N-myc at present. This study aims to screen out hub genes closely related to MYCN, analyze the relationship between hub genes and NB microenvironment, and provide basis for molecular targeted therapy of MYCN positive NB.MethodsWe combined the microarray data of GSE45547 (n=649) and GSE49710 (n=498), screened the DEGs between MYCN positive (n=185) and MYCN negative NB (n=951), performed WGCNA, Lasso regression and Roc analyses on the merged matrix, and obtained the hub genes related to MYCN in the training group. We performed ssGSEA on the experimental group to calculate the infiltration level of 28 kinds of immune cells in each sample, compared the differences of immune cell infiltration between MYCN positive and MYCN negative group. The influences of hub genes on the distribution of each immune cell were also analyzed by ssGSEA. The expression differences of the three hub genes were verified in the E-MTAB-8248 cohort (n=223), and the correlation between hub genes and prognosis of NB was calculated by Kaplan-Meier method in GSE62564 (n=498) and the validation group. We also verified the expression differences of hub genes by qRT-PCR in SK-N-BE(2), SKNDZ, Kelly and SH-SY5Y cell lines.ResultsHere were 880 DEGs including 420 upregulated and 460 downregulated genes in MYCN positive NB in the training group. Overlap of the DEGs and WGCNA networks identified four shared genes, namely, ZNF695, CHEK1, C15ORF42 and EXO1, as candidate hub genes in MYCN positive NB. Three core genes, ZNF695, CHEK1 and C15ORF42, were finally identified by Lasso regression and Roc analyses. ZNF695, CHEK1 and C15ORF42 were highly expressed in MYCN positive NB tissues and cell lines. These three genes were closely related to the prognosis of children with NB. Except that Activated CD4 T cell and Type2 T helper cell increased, the infiltration levels of the other 26 cells decreased significantly in MYCN positive NB tissues. The infiltration levels of Type2 T helper cell and Activated CD4 T cell were also significantly positively correlated with the expression levels of the three hub genes.ConclusionZNF695, CHEK1 and C15ORF42 are highly expressed in MYCN positive NB, and their expression levels are negatively correlated with the prognosis of children with NB. The infiltration levels of Activated CD4 T cell and Type2 T helper cell increased in the microenvironment of MYCN positive NB and were significantly positively correlated with the expression levels of the three hub genes. The results of this study provide that ZNF695, CHEK1 and C15ORF42 may be potential prognostic markers and immunotherapy targets for MYCN positive NB.
Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma
Authors: Chen Yao , Zheng Anfu , Zhang Yao , Xiao Mintao , Zhao Yueshui , Wu Xu , Li Mingxing , Du Fukuan , Chen Yu , Chen Meijuan , Li Wanping , Li Xiaobing , Sun Yuhong , Gu Li , Xiao Zhangang , Shen Jing 
Published: October 2022

BackgroundUveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear.MethodsData were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat.ResultsThe expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells.ConclusionsDysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.
Significance of macrophage infiltration in the prognosis of lung adenocarcinoma patients evaluated by scRNA and bulkRNA analysis
Authors: Zhu Huaiyang , Zheng Chunning , Liu Hongtao , Kong Fanhua , Kong Shuai , Chen Feng , Tian Yuan 
Published: October 2022

PurposeTo investigate the significance of macrophage infiltration to the prognosis of lung adenocarcinoma.MethodsR language bioinformatics analysis technology, was used to obtain macrophage infiltration-related module genes through WGCNA (Weighted Gene Co-Expression Network Analysis). Marker genes of macrophage subtypes were identified using single-cell sequencing of lung adenocarcinoma tissue. Risk score models were constructed and validated using external data cohorts and clinical samples.ResultsAnalysis of cohorts TCGA-LUAD, GSE11969, GSE31210, GSE50081, GSE72094 and GSE8894, revealed a negative correlation between macrophage infiltration and survival. Immunohistochemical analyses of clinical samples were consistent with these data. Based on cell-cluster-markers and TAMs-related-genes, TOP8 genes were obtained (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, and TK1) with a significant association to prognosis. Risk score models including 9 factors (C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65) for prognosis were constructed. The efficacy, stability and generalizability of the risk score models were validated using multiple data cohorts (GSE19188, GSE26939, GSE31210, GSE50081, GSE42127, and GSE72094).ConclusionsMacrophage infiltration negatively correlates with prognosis in patients with lung adenocarcinoma. Based on cell-cluster-markers and TAMs-related-genes, both TOP8 genes (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, TK1) and risk score models using C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65 could predict disease prognosis.
Microglial exosomal miR-466i-5p induces brain injury via promoting hippocampal neuron apoptosis in heatstroke
Authors: Zhu Jie , Chen Yahong , Ji Jingjing , Wang Longyan , Xie Guoqiang , Tang Zhen , Qu Xiangmeng , Liu Zhifeng , Ren Guangli 
Published: October 2022

BackgroundBrain injury is the main cause of poor prognosis in heatstroke (HS) patients due to heat-stress-induced neuronal apoptosis. However, as a new cross-talk way among cells, whether microglial exosomal-microRNAs (miRNAs) are involved in HS-induced neuron apoptosis has not been elucidated.MethodsWe established a heatstroke mouse model and a heat-stressed neuronal cellular model on HT22 cell line. Then, we detected neuron apoptosis by histopathology and flow cytometry. The microglial exosomes are isolated by standard differential ultracentrifugation and characterized. Recipient neurons are treated with the control and HS exosomes, whereas in vivo, the exosomes were injected into the mice tail vein. The internalization of HS microglial exosomes by neurons was tracked. Apoptosis of HT22 was evaluated by flow cytometry and Western blot in vitro, TUNEL assay, and immunohistochemistry in vivo. We screened miR-466i-5p as the mostly upregulated microRNAs in HS exosomes by high-throughput sequencing and further conducted gene ontology (GO) pathway analysis. The effect and mechanism of HS exosomal miR-466i-5p on the induction of neuron apoptosis are demonstrated by nasal delivery of miR-466i-5p antagomir in vivo and transfecting miR-466i-5p mimics to HT22 in vitro.ResultsHS induced an increase in neurons apoptosis. Microglial exosomes are identified and taken up by neurons, which induced HT22 apoptosis in vivo and vitro. HS significantly changed the miRNA profiles of microglial exosomes based on high-throughput sequencing. We selected miR-466i-5p as a target, and upregulated miR-466i-5p induced neurons apoptosis in vivo and vitro experiments. The effects are exerted by targeting Bcl-2, activating caspase-3 to induce neurons apoptosis.ConclusionsWe demonstrate the effect of microglial exosomal miR-466i-5p on neurons apoptosis and reveal potentially Bcl-2/caspase-3 pathway in heatstroke.
Prediction and analysis of periprocedural complications associated with endovascular treatment for unruptured intracranial aneurysms using machine learning
Authors: Tian Zhongbin , Li Wenqiang , Feng Xin , Sun Kaijian , Duan Chuanzhi 
Published: October 2022

BackgroundThe management of unruptured intracranial aneurysm (UIA) remains controversial. Recently, machine learning has been widely applied in the field of medicine. This study developed predictive models using machine learning to investigate periprocedural complications associated with endovascular procedures for UIA.MethodsWe enrolled patients with solitary UIA who underwent endovascular procedures. Periprocedural complications were defined as neurological adverse events resulting from endovascular procedures. We incorporated three machine learning algorithms into our prediction models: artificial neural networks (ANN), random forest (RF), and logistic regression (LR). The Shapley Additive Explanations (SHAP) approach and feature importance analysis were used to identify and prioritize significant features associated with periprocedural complications.ResultsIn total, 443 patients were included. Forty-eight (10.83%) procedure-related complications occurred. In the testing set, the ANN model produced the largest value (0.761) for area under the curve (AUC). The RF model also achieved an acceptable AUC value of 0.735, while the AUC value of the LR model was 0.668. SHAP and feature importance analysis identified distal aneurysm, aneurysm size and treatment modality as most significant features for the prediction of periprocedural complications following endovascular treatment for UIA.ConclusionPeriprocedural complications after endovascular treatment for UIA are not negligible. Prediction of periprocedural complications via machine learning is feasible and effective. Machine learning can serve as a promising tool in the decision-making process for UIA treatment.
Efficacy of twice-daily high-frequency repetitive transcranial magnetic stimulation on associative memory
Authors: Hua Qiang , Zhang Yuanyuan , Li Qianqian , Gao Xiaoran , Du Rongrong , Wang Yingru , Zhou Qian , Zhang Ting , Sun Jinmei , Zhang Lei , Ji Gong-jun , Wang Kai 
Published: October 2022

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.
Development and validation of a novel prognosis prediction model for patients with myelodysplastic syndrome
Authors: Liang Haiping , Feng Yue , Guo Yuancheng , Jian Jinli , Zhao Long , Luo Xingchun , Tao Lili , Liu Bei 
Published: October 2022

BackgroundSomatic mutations are widespread in patients with Myelodysplastic Syndrome (MDS) and are associated with prognosis. However, a practical prognostic model for MDS that incorporates somatic mutations urgently needs to be developed.MethodsA cohort of 201 MDS patients from the Gene Expression Omnibus (GEO) database was used to develop the model, and a single-center cohort of 115 MDS cohorts from Northwest China was used for external validation. Kaplan-Meier analysis was performed to compare the effects of karyotype classifications and gene mutations on the prognosis of MDS patients. Univariate and multivariate Cox regression analyses and Lasso regression were used to screen for key prognostic factors. The shinyapps website was used to create dynamic nomograms with multiple variables. The time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to evaluate the model’s discrimination, accuracy and clinical utility.ResultsSix risk factors (age, bone morrow blast percentage, ETV6, TP53, EZH2, and ASXL1) were considered as predictor variables in the nomogram. The nomogram showed excellent discrimination, with respective the area under the ROC curve (AUC) values of 0.850, 0.839, 0.933 for the training cohort at 1 year, 3 years and 5 years; 0.715, 0.802 and 0.750 for the testing cohort at 1 year, 3 years and 5 years; and 0.668, 0.646 and 0.731 for the external validation cohort at 1 year, 3 years and 5 years. The calibration curves and decision curve showed that the nomogram had good consistency and clinical practical benefit. Finally, a stratified analysis showed that MDS patients with high risk had worse survival outcomes than patients with low risk.ConclusionWe developed a nomogram containing six risk factors, which provides reliable and objective predictions of prognosis for MDS patients.