bluuebunny/crossref_metadata_2025_split huggingface dataset:
Third birth intention of the childbearing-age population in mainland China and sociodemographic differences: a cross-sectional survey
Authors: Yan Zhang , Hui Lin , Wenbin Jiang , Liuxue Lu , Yuemei Li , Bohan Lv , Lili Wei 
Published: December 2021

Abstract
Background
Global fertility declines have become an inevitable trend, and many countries are adopting policies to drive fertility increases. Fertility intention plays an important role in predicting fertility behavior. The Chinese government has recently issued the ‘three-child’ policy, and there is still little research on the third birth intention of the childbearing-age population. Therefore, the aim of this study is to investigate the prevalence and related reasons of third birth intention in the childbearing-age population in mainland China, and analyze the sociodemographic differences.

Method
A cross-sectional survey was conducted in mainland China from June to July 2021. A total of 15,332 childbearing-age participants responded and completed the Fertility Intention Questionnaire online through the Wenjuanxing Platform. Data were explored and analyzed by SPSS (version 22.0) software. Descriptive statistics were used to describe the current situation and reasons of third birth intention. Binary logistic regression analysis was applied to assess the influencing factors in the sociodemographic level.

Results
The mean age of the participants was 32.9 ± 5.94 years. Only 12.2% of participants reported having third birth intention. The subjective norm of having both son and daughter (22.0%) and busy at work (29.2%) accounted for the largest proportion in the reasons of acceptance and rejection, respectively. Age has negative impact on third birth intention (OR = 0.960). Men were 2.209 times more likely to have three children than women (P < 0.001). With the improvement of education and family monthly income, the birth intention shows a downward trend. Compared with Han nationalities, first marriage and city residents, the ethnic minorities, remarriage and rural residents have stronger birth intention (all P < 0.05). And individuals with two existing children are inclined to have the third child (OR = 1.839).

Conclusion
The third birth intention in the childbearing-age population in China is still low after the announcement of the three-child policy. It is necessary to create a favorable fertility context for childbearing-age group with high level of third birth intention, like younger, male, minority, remarriage, with lower education and family monthly income, living in rural and two existing children. Furthermore, removing barriers for those unintended is also prominent to ensure the impetus of policy.
Adapted time-varying covariates Cox model for predicting future cirrhosis development performs well in a large hepatitis C cohort
Authors: Beste Lauren A. , Zhang Xuefei , Su Grace L. , Van Tony , Ioannou George N. , Oselio Brandon , Tincopa Monica , Liu Boang , Singal Amit G. , Zhu Ji , Waljee Akbar K. 
Published: December 2021

Abstract
Background
Patients with hepatitis C virus (HCV) frequently remain at risk for cirrhosis after sustained virologic response (SVR). Existing cirrhosis predictive models for HCV do not account for dynamic antiviral treatment status and are limited by fixed laboratory covariates and short follow up time. Advanced fibrosis assessment modalities, such as transient elastography, remain inaccessible in many settings. Improved cirrhosis predictive models are needed.

Methods
We developed a laboratory-based model to predict progression of liver disease after SVR. This prediction model used a time-varying covariates Cox model adapted to utilize longitudinal laboratory data and to account for antiretroviral treatment. Individuals were included if they had a history of detectable HCV RNA and at least 2 AST-to-platelet ratio index (APRI) scores available in the national Veterans Health Administration from 2000 to 2015, Observation time extended through January 2019. We excluded individuals with preexisting cirrhosis. Covariates included baseline patient characteristics and 16 time-varying laboratory predictors. SVR, defined as permanently undetectable HCV RNA after antiviral treatment, was modeled as a step function of time. Cirrhosis development was defined as two consecutive APRI scores > 2. We predicted cirrhosis development at 1-, 3-, and 5-years follow-up.

Results
In a national sample of HCV patients (n = 182,772) with a mean follow-up of 6.32 years, 42% (n = 76,854) achieved SVR before 2016 and 16.2% (n = 29,566) subsequently developed cirrhosis. The model demonstrated good discrimination for predicting cirrhosis across all combinations of laboratory data windows and cirrhosis prediction intervals. AUROCs ranged from 0.781 to 0.815, with moderate sensitivity 0.703–0.749 and specificity 0.723–0.767.

Conclusion
A novel adaptation of time-varying covariates Cox modeling technique using longitudinal laboratory values and dynamic antiviral treatment status accurately predicts cirrhosis development at 1-, 3-, and 5-years among patients with HCV, with and without SVR. It improves upon earlier cirrhosis predictive models and has many potential population-based applications, especially in settings without transient elastography available.
Medico-economic impact of enhanced rehabilitation after surgery: an exhaustive, nation-wide claims study
Authors: Bizard Frédéric , Boudemaghe Thierry , Delaunay Laurent , Léger Lucas , Slim Karem 
Published: December 2021

Abstract
Background
Study of the medico economic impact of enhanced rehabilitation after surgery (ERAS), by comparing the cost of patient care with or without ERAS, both from the point of view of the hospitals and the Social Security Health Insurance Program.

Methods
Retrospective longitudinal study on matched data from March 1, 2019 to December 31, 2019. The data are extracted from the French prospective payment system. We studied 12 of the most commonly performed in ERAS business segments. The primary outcome was the reduction of the average length of hospital stay and its implications on production costs and excess capacity. We also studied the impact on hospital incomes and Social Security Insurance Program expenses. The potential gain in hospital days was computed by comparing the length of stay of ERAS and non-ERAS cases. The cost reduction was estimated using the mean number of avoidable days of hospitalization, and the mean cost of the stays obtained from the national cost study. Finally, we studied an approximation of the additional expense for the Social Security Health Insurance Program on costs standardized by applying public sector rates.

Results
The average length of stay reduction attributed to ERAS is 1.45 (CI 95% 1.42 to 1.48) day per stay, translating to a cost reduction for the hospitals of € 1060 (CI 95% 995 to 1125) per patient and a total of €65 million (CI 95% 61 to 69). At the same time, the additional expenses for the Social Security Insurance Program can conservatively be approximated to € 1.6 million, breaking into a € 2.2 million increase partially compensated by cost savings of € 0.6 million over subsequent stays for complications. Overall, for each percent of additional ERAS activity over the scope of the study, the marginal cost reduction for the hospitals can be estimated to € 1.8 million (CI 95% 1.7 million to 2.0 million).

Conclusions
Associated with previously known clinical benefits for the patients, these convincing results in terms of economic gain strongly support expanding the adoption of ERAS.
The hidden genomic diversity of ciliated protists revealed by single-cell genome sequencing
Authors: Chen Wenbing , Zuo Changling , Wang Chundi , Zhang Tengteng , Lyu Liping , Qiao Yu , Zhao Fangqing , Miao Miao 
Published: December 2021

AbstractBackgroundCiliated protists are a widely distributed, morphologically diverse, and genetically heterogeneous group of unicellular organisms, usually known for containing two types of nuclei: a transcribed polyploid macronucleus involved in gene expression and a silent diploid micronucleus responsible for transmission of genetic material during sexual reproduction and generation of the macronucleus. Although studies in a few species of culturable ciliated protists have revealed the highly dynamic nature of replicative and recombination events relating the micronucleus to the macronucleus, the broader understanding of the genomic diversity of ciliated protists, as well as their phylogenetic relationships and metabolic potential, has been hampered by the inability to culture numerous other species under laboratory conditions, as well as the presence of symbiotic bacteria and microalgae which provide a challenge for current sequencing technologies. Here, we optimized single-cell sequencing methods and associated data analyses, to effectively remove contamination by commensal bacteria, and generated high-quality genomes for a number of Euplotia species.ResultsWe obtained eight high-quality Euplotia genomes by using single-cell genome sequencing techniques. The genomes have high genomic completeness, with sizes between 68 and 125 M and gene numbers between 14K and 25K. Through comparative genomic analysis, we found that there are a large number of gene expansion events in Euplotia genomes, and these expansions are closely related to the phenotypic evolution and specific environmental adaptations of individual species. We further found four distinct subgroups in the genus Euplotes, which exhibited considerable genetic distance and relative lack of conserved genomic syntenies. Comparative genomic analyses of Uronychia and its relatives revealed significant gene expansion associated with the ciliary movement machinery, which may be related to the unique and strong swimming ability.ConclusionsWe employed single-cell genomics to obtain eight ciliate genomes, characterized the underestimated genomic diversity of Euplotia, and determined the divergence time of representative species in this subclass for the first time. We also further investigated the extensive duplication events associated with speciation and environmental adaptation. This study provides a unique and valuable resource for understanding the evolutionary history and genetic diversity of ciliates.
Molecular evidence of Anaplasma phagocytophilum in olive baboons and vervet monkeys in Kenya
Authors: Masika Sophie Jerusa , Muchemi Gerald Mwangi , Okumu Tequiero Abuom , Mutura Samson , Zimmerman Dawn , Kamau Joseph 
Published: December 2021

Abstract
Background
Nonhuman primates (NHPs) play a significant role in zoonotic spill-overs, serving as either reservoirs, or amplifiers, of multiple neglected tropical diseases, including tick-borne infections. Anaplasma phagocytophilum are obligate intracellular bacteria of the family Anaplasmatacae, transmitted by Ixodid ticks and cause granulocytic anaplasmosis (formerly known as Human Granulocytic Ehrlichiosis (HGE)) in a wide range of wild and domestic mammals and humans too. The aim of this study was to determine whether Anaplasma phagocytophilum was circulating in olive baboons and vervet monkeys in Laikipia County, Kenya.

Results
Some 146 blood samples collected from olive baboons and 18 from vervet monkeys from Mpala Research Center and Ol jogi Conservancy in Laikipia County were screened for the presence of Anaplasma species using conventional Polymerase Chain Reaction (PCR), and then A. phagocytophilum was confirmed by sequencing using conventional PCR targeting 16S rRNA. This study found an overall prevalence of 18.3% for Anaplasma species. DNA sequences confirmed Anaplasma phagocytophilum in olive baboons for the first time in Kenya.

Conclusion
This study provides valuable information on the endemicity of A. phagocytophilum bacteria in olive baboons in Kenya. Future research is needed to establish the prevalence and public health implications of zoonotic A. phagocytophilum isolates and the role of nonhuman primates as reservoirs in the region.
Dynamic changes in genetic diversity, drug resistance mutations, and treatment outcomes of falciparum malaria from the low-transmission to the pre-elimination phase on the islands of São Tomé and Príncipe
Authors: Chen Ying-An , Shiu Tsen-Ju , Tseng Lien-Fen , Cheng Chien-Fu , Shih Wei-Liang , de Assunção Carvalho Arlindo Vicente , Tsai Kun-Hsien 
Published: December 2021

Abstract
Background
With effective vector control and case management, substantial progress has been made towards eliminating malaria on the islands of São Tomé and Príncipe (STP). This study assessed the dynamic changes in the genetic diversity of Plasmodium falciparum, the anti-malarial drug resistance mutations, and malaria treatment outcomes between 2010 and 2016 to provide insights for the prevention of malaria rebounding.

Methods
Polymorphic regions of merozoite surface proteins 1 and 2 (msp1 and msp2) were sequenced in 118 dried blood spots (DBSs) collected from malaria patients who had visited the Central Hospital in 2010–2016. Mutations in the multi-drug resistance I (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfk13) genes were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and sequencing in 111 DBSs. A total of 7482 cases that completed a 28-day follow-up were evaluated for treatment outcomes based on the microscopic results. Regression models were used to characterize factors associated with levels of parasite density and treatment failures.

Results
Parasite strains in STP showed significant changes during and after the peak incidence in 2012. The prevalent allelic type in msp1 changed from K1 to MAD20, and that in msp2 changed from 3D7/IC to FC27. The dominant alleles of drug-resistance markers were pfmdr1 86Y, 184F, D1246, and pfcrt 76 T (Y-F-D-T, 51.4%). The average parasite density in malaria cases declined threefold from low-transmission (2010–2013) to pre-elimination period (2014–2016). Logistic regression models showed that patients with younger age (OR for age = 0.97–0.98, p < 0.001), higher initial parasite density (log10-transformed, OR = 1.44, p < 0.001), and receiving quinine treatment (compared to artemisinin-based combination therapy, OR = 1.91–1.96, p < 0.001) were more likely to experience treatment failures during follow-up.

Conclusions
Plasmodium falciparum in STP had experienced changes in prevalent strains, and increased mutation frequencies in drug-resistance genes from the low-transmission to the pre-elimination settings. Notably, patients with younger age and receiving quinine treatment were more likely to show parasitological treatment failure during follow-up. Therapeutic efficacy should be carefully monitored to inform future treatment policy in STP.
Increased METTL3-mediated m6A methylation inhibits embryo implantation by repressing HOXA10 expression in recurrent implantation failure
Authors: Xue Pingping , Zhou Wenbo , Fan Wenqiang , Jiang Jianya , Kong Chengcai , Zhou Wei , Zhou Jianmei , Huang Xiaoyang , Yang Haiyan , Han Qian , Zhang Bin , Xu Lingyun , Yu Bin , Chen Li 
Published: December 2021

Abstract
Background
Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N6-methyladenosine (m6A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied.

Methods
Global m6A levels and major m6A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m6A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m6A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay.

Results
Global m6A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased β3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m6A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro.

Conclusion
Increased METTL3-mediated m6A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.
TRIM38 triggers the ubiquitination and degradation of glucose transporter type 1 (GLUT1) to restrict tumor progression in bladder cancer
Authors: Wang Xiaojing , He Hongchao , Rui Wenbin , Zhang Ning , Zhu Yu , Xie Xin 
Published: December 2021

Abstract
Background
Loss-of-function mutations or abnormal expressions of E ubiquitin ligases contributes to tumorigenesis. TRIM38 was reported to regulate immunity, inflammatory responses or apoptosis, but its roles in tumor progression remain inconclusive. This study aimed to investigate the functional roles of TRIM38 in bladder cancer to identify effective targets.

Methods
Firstly, the expression data of ubiquitination-associated genes were derived from the TCGA-BLCA cohort. Univariate Cox regression method was utilized to screen prognostic genes. Colony formation assay, Transwell assay, sphere formation assays were used to assess functional roles of TRIM38. TAP/MS assay was used to identify downstream substrates of TRIM38. Fresh clinical BLCA tissues were collected to evaluate the clinicopathological features of patients with different TRIM38 expression. The subcutaneous tumor models were established to determine the drug efficacy of BAY-876.

Results
A list of ubiquitination-associated signature was identified based on the screening in TCGA-BLCA cohort. Subsequent validations revealed that TRIM38 was a significant suppressor in tumors, which was expressed lowly in BLCA. Kaplan–Meier analysis and correlation analysis suggested that patients with low TRIM38 expressions had shorter survival time and advanced clinical characteristics. Targeting TRIM38 reinforced BLCA cells proliferation, migration and stemness. Mechanistically, TRIM38 interacted with GLUT1, thereby promoting its ubiquitinoylation and degradation. Furthermore, TRIM38 deficiency relied on accumulated GLUT1 proteins to enhance BLCA malignant features and cellular glycolytic capacity. We accordingly investigated the efficacy of GLUT1 inhibitor (BAY-876) in BLCA and determined its IC50 values across cell lines. Tumor xenograft models further validated that BAY-876 could effectively suppress the in vivo growth of TRIM38low/− BLCA.

Conclusions
Our results suggested that TRIM38 plays a tumor suppressive role in BLCA pathogenesis and TRIM38/GLUT1 axis is a therapeutic vulnerability for clinical treatment, which possessing great translational significance.
Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer
Authors: Zhou Hanxiao , Gao Yue , Li Xin , Shang Shipeng , Wang Peng , Zhi Hui , Guo Shuang , Sun Dailin , Liu Hongjia , Li Xia , Zhang Yunpeng , Ning Shangwei 
Published: December 2021

Abstract
Background
Emerging evidence has revealed that some long intergenic non-coding RNAs (lincRNAs) are likely to form clusters on the same chromosome, and lincRNA genomic clusters might play critical roles in the pathophysiological mechanism. However, the comprehensive investigation of lincRNA clustering is rarely studied, particularly the characterization of their functional significance across different cancer types.

Methods
In this study, we firstly constructed a computational method basing a sliding window approach for systematically identifying lincRNA genomic clusters. We then dissected these lincRNA genomic clusters to identify common characteristics in cooperative expression, conservation among divergent species, targeted miRNAs, and CNV frequency. Next, we performed comprehensive analyses in differentially-expressed patterns and overall survival outcomes for patients from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) across multiple cancer types. Finally, we explored the underlying mechanisms of lincRNA genomic clusters by functional enrichment analysis, pathway analysis, and drug-target interaction.

Results
We identified lincRNA genomic clusters according to the algorithm. Clustering lincRNAs tended to be co-expressed, highly conserved, targeted by more miRNAs, and with similar deletion and duplication frequency, suggesting that lincRNA genomic clusters may exert their effects by acting in combination. We further systematically explored conserved and cancer-specific lincRNA genomic clusters, indicating they were involved in some important mechanisms of disease occurrence through diverse approaches. Furthermore, lincRNA genomic clusters can serve as biomarkers with potential clinical significance and involve in specific pathological processes in the development of cancer. Moreover, a lincRNA genomic cluster named Cluster127 in DLK1-DIO3 imprinted locus was discovered, which contained MEG3, MEG8, MEG9, MIR381HG, LINC02285, AL132709.5, and AL132709.1. Further analysis indicated that Cluster127 may have the potential for predicting prognosis in cancer and could play their roles by participating in the regulation of PI3K-AKT signaling pathway.

Conclusions
Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.
Gut microbiota modulation as a possible mediating mechanism for fasting-induced alleviation of metabolic complications: a systematic review
Authors: Angoorani Pooneh , Ejtahed Hanieh-Sadat , Hasani-Ranjbar Shirin , Siadat Seyed Davar , Soroush Ahmad Reza , Larijani Bagher 
Published: December 2021

Abstract
Background
Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens.

Method
A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study.

Results
The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid–producing Lachnospiraceae.

Conclusion
The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.