bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between weight-adjusted waist index and non-alcoholic fatty liver disease: a population-based study
Authors: Yu Changhui , He Shiming , Kuang Maobin , Wang Chao , Huang Xin , Sheng Guotai , Zou Yang 
Published: February 2024

Abstract
Background
Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear.

Methods
This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes.

Results
The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction < 0.05). Specifically, compared to the overweight/obese group, the relationship of WWI with NAFLD was significantly stronger in the non-obese group, especially in non-obese men. Finally, based on the results of ROC analysis, we determined that the WWI cut-off point used to identify NAFLD was 9.7675 in men and 9.9987 in women.

Conclusions
This study is the first to establish a positive correlation between WWI and NAFLD. Moreover, assessing the influence of WWI on NAFLD in individuals without obesity may yield more valuable insights compared to those who are overweight or obese.
Factors contributing to the rising prevalence of waterpipe smoking dependence among university students: a cross-sectional study
Authors: Maraqa Beesan , Nazzal Zaher , Baker Noor Abu , Khatib Heyam , Zeyad Marwa , Aburayyan Omar 
Published: February 2024

Abstract
Introduction
Waterpipe smoking (WPS) has been associated with a variety of adverse health effects, consequences, and symptoms of nicotine dependence. This study aims to determine the prevalence of WPS dependence among Palestinian university waterpipe smoking students, their normative beliefs about WPS, and their relationship to dependence.

Methods
A cross-sectional study of current WPS university students at five major Palestinian universities was conducted from September to December 2022. Participants were recruited using convenient sampling, and data collection was carried out via an interviewer-administered questionnaire. We assessed students’ WPS dependence using the Lebanese Waterpipe Dependence Scale. We used the Poisson regression model with robust variance to analyze factors independently associated with high WPS dependence.

Results
The study included 746 current WPS university students. Results revealed a high prevalence of WPS dependence, with 69.4% (95%CI: 66.0-72.7%) exhibiting high dependence. Factors contributing to high WPS dependence included dual cigarette smoking (aPR: 1.18; 95%CI: 1.12–1.25), studying medical sciences (aPR: 1.13; 95%CI: 1.10–1.18), friends’ approval of WPS (aPR: 1.25; 95%CI: 1.17–1.34), daily WPS frequency (aPR: 1.98; 95%CI: 1.39–2.23), spending more than 50% of daily allowance on WPS (aPR: 1.37; 95%CI: 1.10–1.64), and morning WPS sessions (aPR: 1.97; 95%CI: 1.31–2.27). The study highlighted the influence of social factors, such as peers’ approval and perceived prevalence, on WPS dependence.

Conclusions
WPS dependence is prevalent among university students, and it is associated with morning WPS, dual smoking, and increased WPS frequency. Notably, peer and cultural factors are essential primary motivators. As a result, it is critical to incorporate WPS considerations into Palestine’s antismoking health promotion program. Therefore, it is vital to incorporate WPS into the Palestinian antismoking health promotion policy, and the health education of adolescents regarding the dangers of WPS should coincide with antismoking initiatives.
Metabolic engineering of Synechocystis sp. PCC 6803 for the improved production of phenylpropanoids
Authors: Kukil Kateryna , Lindberg Pia 
Published: February 2024

Abstract
Background
Phenylpropanoids are a large group of plant secondary metabolites with various biological functions, derived from aromatic amino acids. Cyanobacteria are promising host organisms for sustainable production of plant phenylpropanoids. We have previously engineered Synechocystis sp. PCC 6803 to produce trans-cinnamic acid (tCA) and p-coumaric acid (pCou), the first intermediates of phenylpropanoid pathway, by overexpression of phenylalanine- and tyrosine ammonia lyases. In this study, we aimed to enhance the production of the target compounds tCA and pCou in Synechocystis.

Results
We eliminated the 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, which is a competing pathway consuming tyrosine and, possibly, phenylalanine for tocopherol synthesis. Moreover, several genes of the terminal steps of the shikimate pathway were overexpressed alone or in operons, such as aromatic transaminases, feedback insensitive cyclohexadienyl dehydrogenase (TyrC) from Zymomonas mobilis and the chorismate mutase (CM) domain of the fused chorismate mutase/prephenate dehydratase enzyme from Escherichia coli. The obtained engineered strains demonstrated nearly 1.5 times enhanced tCA and pCou production when HPPD was knocked out compared to the parental production strains, accumulating 138 ± 3.5 mg L−1 of tCA and 72.3 ± 10.3 mg L−1 of pCou after seven days of photoautotrophic growth. However, there was no further improvement when any of the pathway genes were overexpressed. Finally, we used previously obtained AtPRM8 and TsPRM8 Synechocystis strains with deregulated shikimate pathway as a background for the overexpression of synthetic constructs with ppd knockout.

Conclusions
HPPD elimination enhances the tCA and pCou productivity to a similar extent. The use of PRM8 based strains as a background for overexpression of synthetic constructs, however, did not promote tCA and pCou titers, which indicates a tight regulation of the terminal steps of phenylalanine and tyrosine synthesis. This work contributes to establishing cyanobacteria as hosts for phenylpropanoid production.
The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization
Authors: Sun Juan , Li Jie , Pantopoulos Kostas , Liu Yuqin , He Yixuan , Kang Weiming , Ye Xin 
Published: February 2024

Abstract
Background and purpose
Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis.

Methods
GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan–Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients.

Results
Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan–Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression.

Conclusions
Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential.
Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.
Socioeconomic and geographic variations of disabilities in India: evidence from the National Family Health Survey, 2019–21
Authors: Rashmi Rashmi , Mohanty Sanjay K. 
Published: February 2024

Abstract
Background
Increasing disability is of global and national concern. Lack of evidence on disability across socioeconomic groups and geographic levels (especially small areas) impeded interventions for these disadvantaged subgroups. We aimed to examine the socioeconomic and geographic variations in disabilities, namely hearing, speech, visual, mental, and locomotor, in Indian participants using cross-sectional data from the National Family Health Survey 2019–2021.

Methods
Using data from 27,93,971 individuals, we estimated age-sex-adjusted disability rates at the national and sub-national levels. The extent of socioeconomic variations in disabilities was explored using the Erreygers Concentration Index and presented graphically through a concentration curve. We adopted a four-level random intercept logit model to compute the variance partitioning coefficient (VPC) to assess the significance of each geographical unit in total variability. We also calculated precision-weighted disability estimates of individuals across 707 districts and showed their correlation with within-district or between-cluster standard deviation.

Results
We estimated the prevalence of any disability of 10 per 1000 population. The locomotor disability was common, followed by mental, speech, hearing, and visual. The concentration index of each type of disability was highest in the poorest wealth quintile households and illiterate 18 + individuals, confirming higher socioeconomic variations in disability rates. Clusters share the largest source of geographic variation for any disability (6.5%), hearing (5.8%), visual (24.3%), and locomotor (17.4%). However, States/Union Territories (UTs) account for the highest variation in speech (3.7%) and mental (6.5%) disabilities, where the variation at the cluster level becomes negligible. Districts with the highest disability rates were clustered in Madhya Pradesh, Maharashtra, Karnataka, Tamil Nadu, Telangana, and Punjab. Further, we found positive correlations between the district rates and cluster standard deviations (SDs) for disabilities.

Conclusions
Though the growing disability condition in India is itself a concerning issue, wide variations across socioeconomic groups and geographic locations indicate the implementation of several policy-relevant implications focusing on these vulnerable chunks of the population. Further, the critical importance of small-area variations within districts suggests the design of strategies targeting these high-burden areas of disabilities.
Two-dimensional nanomaterials induced nano-bio interfacial effects and biomedical applications in cancer treatment
Authors: Wang Yan , Zhang Xiao , Yue Hua 
Published: February 2024

AbstractTwo-dimensional nanomaterials (2D NMs), characterized by a large number of atoms or molecules arranged in one dimension (typically thickness) while having tiny dimensions in the other two dimensions, have emerged as a pivotal class of materials with unique properties. Their flat and sheet-like structure imparts distinctive physical, chemical, and electronic attributes, which offers several advantages in biomedical applications, including enhanced surface area for efficient drug loading, surface-exposed atoms allowing precise chemical modifications, and the ability to form hierarchical multilayer structures for synergistic functionality. Exploring their nano-bio interfacial interactions with biological components holds significant importance in comprehensively and systematically guiding safe applications. However, the current lack of in-depth analysis and comprehensive understanding of interfacial effects on cancer treatment motivates our ongoing efforts in this field. This study provides a comprehensive survey of recent advances in utilizing 2D NMs for cancer treatment. It offers insights into the structural characteristics, synthesis methods, and surface modifications of diverse 2D NMs. The investigation further delves into the formation of nano-bio interfaces during their in vivo utilization. Notably, the study discusses a wide array of biomedical applications in cancer treatment. With their potential to revolutionize therapeutic strategies and outcomes, 2D NMs are poised at the forefront of cancer treatment, holding the promise of transformative advancements.
Graphical Abstract
Evaluation of serum adiponectin as a marker of insulin resistance in women with polycystic ovarian syndrome: a comparative cross-sectional study
Authors: Runsewe Olugbenga Ojatokunbo , Adewunmi Abiodun Adeniyi , Olorunfemi Gbenga , Ottun Abimbola Tawaqualit , Olumodeji Ayokunle Moses , Ogungbemile Babalola , Runsewe-Abiodun Tamramat Iyabo 
Published: February 2024

Abstract
Background
Insulin resistance (IR) is known to be prevalent amongst women with polycystic ovarian syndrome (PCOS). Its presence has been linked to chronic anovulation and marked long term complications in women. Hence, identification and treatment of IR in women with PCOS is required to prevent the metabolic and reproductive complications of the disease. The aim of this study is to determine if serum adiponectin could be used as a surrogate marker for insulin resistance among women with PCOS.

Materials and methods
A total number of 148 consenting women with PCOS diagnosed using the Rotterdam criteria were recruited for this study. Fifty-two of these women had insulin resistance were compared with 96 of the women who did not have insulin resistance. The serum Adiponectin levels, fasting blood glucose and fasting insulin levels were assayed in all study participants. Insulin resistance was assessed in all the study participants using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Data were analyzed using relevant inferential statistics at 95% confidence interval and p value of < 0.05.

Results
The prevalence of insulin resistance among the study participants was 35.1%. Majority of the women (83.1%) had a high body mass index (BMI). More than half (68.2%) of the participants were in the age range of 21-30years and 76.4% (113) were nulliparous. There was no statistically significant difference in the median adiponectin level among insulin resistant (3.735 ug/ml) and non-insulin resistant participants vs. (3.705 ug/ml) (p = 0.6762). Both univariate and multivariate regression analysis did not show a statistically significant relationship between adiponectin and insulin resistance in PCOS.

Conclusion
The prevalence of insulin resistance in women with PCOS is high and serum adiponectin is not a suitable surrogate marker of insulin resistance in women with PCOS.
RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling
Authors: Fang Yuan , Tang WeiQiang , Qu Siming , Li ZhiTao , Zhang XiaoLi , Miao YingLei , Zeng Zhong , Huang HanFei 
Published: February 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms.

Methods
The expression and clinical feature of RBBP7 were evaluated using bioinformatics analysis and the assessment of clinical HCC samples. CCK8 and colony formation were employed to estimate cell proliferation function of RBBP7. Aerobic glycolysis levels of RBBP7 were evaluated by measuring ATP levels, lactic acid production, glucose uptake capacity, and the expression of relevant enzymes (PFKM, PKM2, and LDHA). The phosphorylation levels in PI3K/AKT signaling were measured by western blotting. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The proliferation- and glycolysis-associated proteins were assessed using immunofluorescence staining in vivo.

Results
We found that RBBP7 is expressed at high levels in HCC and predicts poor survival. Functional assays showed that RBBP7 promoted HCC proliferation and glycolysis. Mechanistically, it was demonstrated that RBBP7 activates the PI3K/AKT pathway, a crucial pathway in glycolysis, contributing to the progression of HCC. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7.

Conclusions
RBBP7, which is up-regulated by SP1, promotes HCC cell proliferation and glycolysis through the PI3K/AKT pathway. The findings of this study suggest that RBBP7 is a potential biomarker for HCC.
HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1
Authors: You Hang , Song Guojing , Xu Zhizhen , Chen Saipeng , Shen Wenhao , Liu Heting , Deng Bingqian , Li Jun , Huang Gang 
Published: February 2024

Abstract
Background
Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression.

Methods
HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays.

Results
HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction.

Conclusions
We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression.

Graphical Abstract
Gut microbial metabolites SCFAs and chronic kidney disease
Authors: He Meng , Wei Wenqian , Zhang Yichen , Xiang Zhouxia , Peng Dan , Kasimumali Ayijiaken , Rong Shu 
Published: February 2024

AbstractThe global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD’s development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.
Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with colorectal cancer
Authors: Zou Shaomin , Yang Chao , Zhang Jieping , Zhong Dan , Meng Manqi , Zhang Lu , Chen Honglei , Fang Lekun 
Published: February 2024

Abstract
Background
Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear.

Methods
We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.

Results
We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.

Conclusion
Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.