bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer
Authors: Cong Rong , Li Mingyang , Xu Wan , Ma Xiaoxin , Wang Shuhe 
Published: November 2023

Abstract
Background
Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application.

Methods
A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker’s prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves.

Results
Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810–0.960) and 0.850 (95% CI, 0.761–0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866–0.940) and 0.825 (95% CI, 0.711–0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks.

Conclusions
Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.
A qualitative study exploring the perceptions of children, parents and school staff towards the development and implementation of school lunch provision within primary schools in the Netherlands
Authors: Rongen Frédérique C. , Coosje Dijkstra S. , Hupkens Tobie H. , Vingerhoeds Monique H. , Seidell Jacob C. , van Kleef Ellen 
Published: November 2023

Abstract
Background
There is no tradition of serving school lunches in primary schools in the Netherlands. Most children tend to bring their own packed lunch, however these are often nutritionally suboptimal. While school lunch provision can aid healthy eating behavior amongst children, its introduction would constitute a profound change for children, parents and school staff. Therefore, this qualitative study aims to explore children’s, parents and school staffs’ perceptions of both the current lunch situation and the implementation of school lunch provision within primary schools in the Netherlands.

Methods
In this qualitative study we conducted nine interviews with school principals, 98 interviews with children, and held six focus groups with teachers and six with parents at primary schools in two Dutch cities. The data was analysed via iterative coding.

Results
The results showed that most children and parents are satisfied with the current lunch situation, although existing school food policies are not always put in place. Most teachers felt that children had insufficient time to consume their lunch in the current situation. The children were generally positive about the idea of a school lunch, and stressed that it was important to have the ability to choose. While both parents and school staff saw school lunch provision as an opportunity to educate families about healthy food options, they also expressed concern about who would be responsible, as well as the financial and organizational implications of its introduction.

Conclusions
Perceptions of children, parents and school staff about a school provided lunch are mixed. A complex intervention such as a new school lunch program is difficult to envisage for all parties involved and more research is needed regarding the effects, organization, logistics and the costs of school lunch provision in the Netherlands.
The transcriptional factor Clr-5 is involved in cellulose degradation through regulation of amino acid metabolism in Neurospora crassa
Authors: Xue Fanglei , Zhao Zhen , Gu Shuying , Chen Meixin , Xu Jing , Luo Xuegang , Li Jingen , Tian Chaoguang 
Published: November 2023

Abstract
Background
Filamentous fungi are efficient degraders of plant biomass and the primary producers of commercial cellulolytic enzymes. While the transcriptional regulation mechanisms of cellulases have been continuously explored in lignocellulolytic fungi, the induction of cellulase production remains a complex multifactorial system, with several aspects still largely elusive.

Results
In this study, we identified a Zn2Cys6 transcription factor, designated as Clr-5, which regulates the expression of cellulase genes by influencing amino acid metabolism in Neurospora crassa during growth on cellulose. The deletion of clr-5 caused a significant decrease in secreted protein and cellulolytic enzyme activity of N. crassa, which was partially alleviated by supplementing with yeast extract. Transcriptomic profiling revealed downregulation of not only the genes encoding main cellulases but also those related to nitrogen metabolism after disruption of Clr-5 under Avicel condition. Clr-5 played a crucial role in the utilization of multiple amino acids, especially leucine and histidine. When using leucine or histidine as the sole nitrogen source, the Δclr-5 mutant showed significant growth defects on both glucose and Avicel media. Comparative transcriptomic analysis revealed that the transcript levels of most genes encoding carbohydrate-active enzymes and those involved in the catabolism and uptake of histidine, branched-chain amino acids, and aromatic amino acids, were remarkably reduced in strain Δclr-5, compared with the wild-type N. crassa when grown in Avicel medium with leucine or histidine as the sole nitrogen source. These findings underscore the important role of amino acid metabolism in the regulation of cellulase production in N. crassa. Furthermore, the function of Clr-5 in regulating cellulose degradation is conserved among ascomycete fungi.

Conclusions
These findings regarding the novel transcription factor Clr-5 enhance our comprehension of the regulatory connections between amino acid metabolism and cellulase production, offering fresh prospects for the development of fungal cell factories dedicated to cellulolytic enzyme production in bio-refineries.
Clinical application of a digital semi-rigid bridge space maintainer fabricated from polyetheretherketone for premature loss of primary molars
Authors: Wang Qi , Zhang Zhenzhen , Zhong Sheng , Liu Jiajia , Hu Ying , Zhou Ziling , Zhang Caidi , Bai Shizhu , Wu Li’an 
Published: November 2023

Abstract
Background
Premature loss of primary molars can be treated with a band loop space maintainer (SM). However, fabricating a conventional band loop SM requires multiple clinical and laboratory procedures, which can potentially affect the accuracy of the SM. Moreover, the conventional SM is unable to fully restore masticatory function and maintain the vertical dimension of the edentulous space. In this current study, a fully digital workflow to fabricate a semi-rigid bridge SM made from polyetheretherketone (PEEK) has been described and evaluated for its clinical effectiveness.

Methods
A total of 15 children (eight males and seven females) between the ages of 4–8 years, who experienced the premature loss of a single primary molar, were included in this study. Digital impressions were taken using the CEREC CAD/CAM chair system and imported into CAD software to design the semi-rigid bridge SM, which was fabricated using PEEK block as the maintainer material. The digital SM was tried-in and bonded to the abutment with resin cement. The edentulous space was measured immediately after bonding (T0) and 1 month (T1), 3 months (T2), and 6 months (T3) after treatment. The periodontal condition and mobility of the SM and abutment were also examined.

Results
The use of digital impressions resulted in a decreased occurrence of the pharyngeal reflex. The digital semi-rigid bridge SM, fabricated with PEEK, was both convenient and aesthetically pleasing, and successfully restored the anatomy and masticatory function of the missing primary molar. None of the 15 semi-rigid bridge SMs or abutments became loose or fell off during the study, and only one child presented with gingivitis. Furthermore, the difference in the edentulous space at T0, T1, T2, and T3 was not statistically significant (all P > 0.05).

Conclusions
The digital semi-rigid bridge SM fabricated with PEEK was clinically effective in maintaining the missing space and had advantages over the traditional band/crown loop SM.
Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin
Authors: Sun Shao-Qian , Du Feng-Xiang , Zhang Li-Hua , Hao-Shi  , Gu Fu-Ying , Deng Yu-Lin , Ji Yi-Zhi 
Published: November 2023

Abstract
Purpose
Neuroblastoma (NB) is the most common solid malignancy in children. Despite current intensive treatment, the long-term event-free survival rate is less than 50% in these patients. Thus, patients with NB urgently need more valid treatment strategies. Previous research has shown that STAT3 may be an effective target in high-risk NB patients. However, there are no effective inhibitors in clinical evaluation with low toxicity and few side effects. Astaxanthin is a safe and natural anticancer product. In this study, we investigated whether astaxanthin could exert antitumor effects in the SK-N-SH neuroblastoma cancer cell line.

Method
MTT and colony formation assays were used to determine the effect of astaxanthin on the proliferation and colony formation of SK-N-SH cells. Flow cytometry assays were used to detect the apoptosis of SK-N-SH cells. The migration and invasion ability of SK-N-SH cells were detected by migration and invasion assays. Western blot and RT-PCR were used to detect the protein and mRNA levels. Animal experiments were carried out and cell apoptosis in tissues were assessed using a TUNEL assay.

Result
We confirmed that astaxanthin repressed proliferation, clone formation ability, migration and invasion and induced apoptosis in SK-N-SH cells through the STAT3 pathway. Furthermore, the highest inhibitory effect was observed when astaxanthin was combined with si-STAT3. The reason for this may be that the combination of astaxanthin and si-STAT3 can lower STAT3 expression further than astaxanthin or si-STAT3 alone.

Conclusion
Astaxanthin can exert anti-tumor effect on SK-N-SH cells. The inhibitory effect was the higher when astaxanthin was combined with si-STAT3.
Maternal satisfaction on quality of childhood vaccination services and its associated factors at public health centers in Addis Ababa, Ethiopia
Authors: Tesfaye Eyasu , Debie Ayal , Sisay Fasil , Tafere Tesfahun Zemene 
Published: November 2023

Abstract
Background
Vaccination is one of the most important public health interventions to reduce child mortality and morbidity. In Ethiopia, about 472,000 children die each year by vaccine-preventable diseases. A satisfied mother is assumed to use the services and complies with the service provider for better health care outcomes. However, there was no adequate evidence regarding maternal satisfaction with quality of childhood vaccination services. This study aimed to assess maternal satisfaction on quality of childhood vaccination services and its associated factors at public health centers in Addis Ababa, Ethiopia.

Methods
A facility-based cross-sectional study was conducted from 12 July to 12 August 2021 at public health centers in Addis Ababa, Ethiopia. A total of 366 mothers (caretakers) of under one-year-old children participated in the study. A systematic sampling technique with an interviewer-administered questionnaire and inventory checklist were used to collect the data. A binary logistic regression model was fitted. Adjusted Odds Ratio (AOR) with 95% confidence interval (CI) and p-value < 0.05 were used to identify the factors associated with the outcome.

Results
Nearly two-thirds (61.2%) of mothers (caretakers) were satisfied with the quality of childhood vaccination services. Service providers’ greeting [AOR = 1.60; 95%CI: 1.37–1.99] and information about the types of vaccines [AOR = 1.54; 95%CI: 1.32–1.89] were positively associated with maternal satisfaction. On the contrary, long waiting time of mothers (caretakers) to receive services [AOR = 0.29; 95%CI: 0.14–0.62] was negatively associated with services.

Conclusion
The overall maternal satisfaction towards the quality of childhood vaccination services in this study was found to be low. Minimizing waiting time at the health facility, enhancing greetings and providing adequate information regarding childhood vaccination for mothers (caretakers) improved their satisfaction with the services.
Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1
Authors: Birgersson Madeleine , Indukuri Rajitha , Lindquist Linnéa , Stepanauskaite Lina , Luo Qing , Deng Qiaolin , Archer Amena , Williams Cecilia 
Published: November 2023

Abstract
Background
Estrogen receptor beta (ERβ, Esr2) plays a pivotal role in folliculogenesis and ovulation, yet its exact mechanism of action is mainly uncharacterized.

Results
We here performed ERβ ChIP-sequencing of mouse ovaries followed by complementary RNA-sequencing of wild-type and ERβ knockout ovaries. By integrating the ERβ cistrome and transcriptome, we identified its direct target genes and enriched biological functions in the ovary. This demonstrated its strong impact on genes regulating organism development, cell migration, lipid metabolism, response to hypoxia, and response to estrogen. Cell-type deconvolution analysis of the bulk RNA-seq data revealed a decrease in luteal cells and an increased proportion of theca cells and a specific type of cumulus cells upon ERβ loss. Moreover, we identified a significant overlap with the gene regulatory network of liver receptor homolog 1 (LRH-1, Nr5a2) and showed that ERβ and LRH-1 extensively bound to the same chromatin locations in granulosa cells. Using ChIP-reChIP, we corroborated simultaneous ERβ and LRH-1 co-binding at the ERβ-repressed gene Greb1 but not at the ERβ-upregulated genes Cyp11a1 and Fkbp5. Transactivation assay experimentation further showed that ERβ and LRH-1 can inhibit their respective transcriptional activity at classical response elements.

Conclusions
By characterizing the genome-wide endogenous ERβ chromatin binding, gene regulations, and extensive crosstalk between ERβ and LRH-1, along with experimental corroborations, our data offer genome-wide mechanistic underpinnings of ovarian physiology and fertility.
Epidemiology and Genomic characteristics of arenavirus in rodents from the southeast coast of P.R. China
Authors: Xie Qinghua , Zhu Changqiang , Ai Lele , Nie Danyue , Wu Yifan , Wang Chongcai , He Ji , Tan Weilong , Zhang Lingling 
Published: November 2023

Abstract
Background
Wenzhou virus (WENV), a member of the Mammarenavirus genus in the Arenaviridae family, has been detected in wild rodents from eight provinces in China, including Zhejiang, Shandong, Hainan, Xinjiang, Hunan, Guangdong, Yunnan, and Jiangxi provinces, and some countries from Southeast Asia. The IgG-antibodies of WENV have been detected in both healthy populations and patients with unknown fever and respiratory symptoms. However, the potential harmfulness of WENV to humans has been underestimated due to mild symptoms after infection, similar to respiratory diseases. Thus, it is imperative to enhance the surveillance of WENV in wild rodents, particularly Rattus norvegicus, and continuously monitor its prevalence.

Results
From 2017 to 2021, a total of 390 wild rodents were collected from six provinces in the eastern and southern coastal areas, containing nine species of rats. Samples of each tissue were collected, and PCR amplified for identification. Four R. norvegicus samples were detected to be WENV-positive. No genomic sequence of WENV was detected in Rattus flavipectus, Rattus losea, Suncus murinus, Apodemus agrarius, Mus musculus, Microtus fortis, Micromys minutus, and Niviventer niviventer from Jiangsu, Zhejiang, Fujian, Hainan, Guangdong and Guangxi provinces. Three genomic sequences were identified to be WENV by phylogenetic analysis. The full-length sequences of HAIKOU-40 were amplified in R. norvegicus from Hainan, which showed a close relationship to Wufeng/ WFS, sharing 84.5–89.4% homology at the nucleotide level and 91.6–98.9% homology at the amino acid level. Phylogenetic analysis revealed that HAIKOU-40 formed an Asia-specific cluster with all WENVs and Loie River mammarenavirus (LORV), provisionally named Asian ancestry. This cluster has diverged earlier from the remaining mammarenavirus. The sequences obtained in Xiamen, Fujian province showed more than 90% nucleotide identities with WENV, which may be a strain of WENV. Additionally, the sequence of Wuxi-87 which was a positive sequence detected in Wuxi, Jiangsu province exhibited 83% nucleotide identity with Lassa virus (LASV). Further efforts will be made to isolate and identify this virus strain, verify the relationship between Wuxi-87 and LASV, and confirm whether R. norvegicus is a new host of LASV.

Conclusions
In this study, we conducted a systematic examination of the prevalence of WENV among rodents on the southeast coast of China. Additionally, we characterized the genome of a newly discovered WENV strain, that confirmed the role of R. norvegicus in the transmission of WENV. This highlights the importance of investigating the prevalence of WENV in both wild rodents and humans.
Distribution of water turnover by sex and age as estimated by prediction equation in Japanese adolescents and adults: the 2016 National Health and Nutrition Survey, Japan
Authors: Watanabe Daiki , Inoue Yumiko , Miyachi Motohiko 
Published: November 2023

Abstract
Background
Although water is essential to the maintenance of health and life, standard values for human water requirements are yet to be determined. This study aimed to evaluate the distribution of water turnover (WT) according to sex and age, estimated using a prediction equation, in Japanese adolescents and adults.

Methods
This cross-sectional study used data from the 2016 National Health and Nutrition Survey, Japan. Data were obtained from electronically available aggregated reports in the survey’s official website. Participants aged between 15 and 80 years (10,546 men, 12,355 women) were selected using stratified random sampling. WT was calculated considering lifestyle and environmental factors, and using an equation (coefficient of determination = 0.471) previously developed by the international doubly labelled water (DLW) database group. As data on physical activity levels (PAL) were not collected in the survey, we used two evaluation methods: (1) energy intake assessed by dietary records and (2) total energy expenditure measured by the DLW method reported in previous Japanese studies, divided by basal metabolic rate predicted using the equation. We evaluated the relationship between WT and age using a restricted cubic spline model.

Results
The average WT for the 15–19, 20–29, 30–39, 40–49, 50–59, 60–69, and ≥ 70 years was 3291, 3151, 3213, 3243, 3205, 3104, and 2790 ml/day, respectively in men, and 2641, 2594, 2741, 2739, 2753, 2707, and 2482 ml/day, respectively in women. In the spline model, WT showed an inverse association with age in men older than 50 years, whereas women showed a reverse U-shaped relationship between WT and age (p for non-linearity < 0.001), although results differed with body weight adjustment. Similar results were found for both PAL evaluation methods, and the range of WT per body weight was 45–56 ml/day for both sexes.

Conclusions
We determined the standard values of WT in Japanese population using a prediction equation and national large-scale survey data. These findings may be useful for setting water requirements for dietary guidelines in future.
Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study
Authors: Guo Junchen , Liu XiaoXuan , Wang Zeng , Lu Rongzhe , Liu Yige , Zhang Yiying , Tian Wei , Fang Shaohong , Wang Shanjie , Yu Bo 
Published: November 2023

Abstract
Background
The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD.

Methods
The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk.

Results
Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31–2.20) for all-cause mortality, and 2.00 (1.39–2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001).

Conclusion
MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.
Natural killer cells in the central nervous system
Authors: Ning Zhiyuan , Liu Ying , Guo Daji , Lin Wei-Jye , Tang Yamei 
Published: November 2023

AbstractNatural killer (NK) cells are essential components of the innate lymphoid cell family that work as both cytotoxic effectors and immune regulators. Accumulating evidence points to interactions between NK cells and the central nervous system (CNS). Here, we review the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions, with a focus on normal aging, CNS autoimmune diseases, neurodegenerative diseases, cerebrovascular diseases, and CNS infections. We highlight the crosstalk between NK cells and diverse cell types in the CNS and the potential value of NK cells as novel therapeutic targets for CNS diseases.