bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel lipid indicators and the risk of type 2 diabetes mellitus among Chinese hypertensive patients: findings from the Guangzhou Heart Study
Authors: Deng Hai , Hu Peng , Li Huoxing , Zhou Huanning , Wu Xiuyi , Yuan Maohua , Duan Xueru , Lao Miaochan , Wu Chuchu , Zheng Murui , Lao Xiang Qian , Zhao Wenjing , Liu Xudong 
Published: October 2022

Abstract
Background
Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients.

Methods
This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression.

Results
The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all PNon-linear < 0.001).

Conclusions
The results found that among hypertensive patients, HTGW and a higher level of TyG, LAP, and VAI were associated with an elevated risk of T2DM. The findings suggested that HTGW, TyG, LAP, and VAI may serve as simple and effective tools for T2DM risk assessment in the prevention and management of main chronic diseases.
Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin
Authors: Yu Shiqin , Li Mingjia , Gao Song , Zhou Jingwen 
Published: October 2022

Abstract
Background
Dihydroquercetin (DHQ), a powerful bioflavonoid, has a number of health-promoting qualities and shows potential as a treatment for a number of disorders. Dihydroquercetin biosynthesis is a promising solution to meet the rising demand for dihydroquercetin. However, due to the significant accumulation of eriodietyol (ERI), naringenin (NAR), dihydrokaempferol (DHK), and other metabolites, the yield of DHQ biosynthesis is low. As a result, this is the hindrance to the biosynthesis of DHQ.

Results
In this study, we proposed several strategies to enhance the product formation and reduce the metabolites in accumulation. The flavonoid 3′-hydroxylase (F3′H) and cytochrome P450 reductase from different species were co-expressed in S. cerevisiae, and the best strain expressing the P450-reductase enzyme complex (SmF3′H/ScCPR) yielded 435.7 ± 7.6 mg/L of ERI from NAR in the deepwell microplate. The product conversion rate was improved further by mutating the predicted potential ubiquitination sites to improve SmF3′H stability, resulting in a 12.8% increase in titre using the mutant SmF3′H (K290R). Besides, different F3Hs from various sources and promoters were tested for the improved DHQ production, with the best strain producing 381.2 ± 10.7 mg/L of DHQ from 1 g/L of NAR, suggesting the temporal regulation the expression of F3H is important for maximization the function of F3′H and F3H.

Conclusion
This study offers effective strategies for improving DHQ production from NAR and could be used as a reference for related research.
Identification of acetic acid sensitive strains through biosensor-based screening of a Saccharomyces cerevisiae CRISPRi library
Authors: Mormino Maurizio , Lenitz Ibai , Siewers Verena , Nygård Yvonne 
Published: October 2022

Abstract
Background
Acetic acid tolerance is crucial for the development of robust cell factories for conversion of lignocellulosic hydrolysates that typically contain high levels of acetic acid. Screening mutants for growth in medium with acetic acid is an attractive way to identify sensitive variants and can provide novel insights into the complex mechanisms regulating the acetic acid stress response.

Results
An acetic acid biosensor based on the Saccharomyces cerevisiae transcription factor Haa1, was used to screen a CRISPRi yeast strain library where dCas9-Mxi was set to individually repress each essential or respiratory growth essential gene. Fluorescence-activated cell sorting led to the enrichment of a population of cells with higher acetic acid retention. These cells with higher biosensor signal were demonstrated to be more sensitive to acetic acid. Biosensor-based screening of the CRISPRi library strains enabled identification of strains with increased acetic acid sensitivity: strains with gRNAs targeting TIF34, MSN5, PAP1, COX10 or TRA1.

Conclusions
This study demonstrated that biosensors are valuable tools for screening and monitoring acetic acid tolerance in yeast. Fine-tuning the expression of essential genes can lead to altered acetic acid tolerance.
The prognostic value of arachidonic acid metabolism in breast cancer by integrated bioinformatics
Authors: Li Wenge , Guo Xiaoyu , Chen Changzheng , Li Juanjuan 
Published: October 2022

Abstract
Background
As the second cause of cancer death in women, breast cancer has become a worldwide priority. Previous studies based on tumour cell lines demonstrated that arachidonic acid (AA) and its metabolites promote cancer development. However, recent studies based on the tumour microenvironment revealed the antitumour effect of AA metabolism. Therefore, it is essential to reevaluate and elucidate the effect of AA metabolism on breast cancer.

Methods
Raw data were obtained from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) databases. The AA metabolic score of each sample, enrichment of differentially expressed genes (DEGs) and immune infiltration were analysed by bioinformatics. Cox regression and least absolute shrinkage and selection operator regression were performed to establish an AA metabolism prognostic signature. An AA metabolism related nomogram for predicting the survival probability of patients was built.

Result
AA metabolism was related to good prognosis in the TCGA-BRCA and METABRIC cohort. DEGs enrichment suggested that the upregulated DEGs of the high AA metabolism group were significantly enriched in immune-related pathways. The high AA metabolism group was infiltrated with more CD8+ T cells and activated NK cells. An AA metabolic signature (SPINK8, KLRB1, APOD and PIGR) was constructed for breast cancer prognosis.

Conclusion
The study indicated that a high level of AA metabolism may be a biomarker for good prognosis in breast cancer, providing a possible explanation for the discouraging effect of cyclooxygenase inhibitors in cancer therapy. Moreover, a novel AA metabolic prognostic signature was constructed in the study, providing a novel strategy for breast cancer.
In vivo fluorescence imaging: success in preclinical imaging paves the way for clinical applications
Authors: Refaat Ahmed , Yap May Lin , Pietersz Geoffrey , Walsh Aidan Patrick Garing , Zeller Johannes , del Rosal Blanca , Wang Xiaowei , Peter Karlheinz 
Published: October 2022

AbstractAdvances in diagnostic imaging have provided unprecedented opportunities to detect diseases at early stages and with high reliability. Diagnostic imaging is also crucial to monitoring the progress or remission of disease and thus is often the central basis of therapeutic decision-making. Currently, several diagnostic imaging modalities (computed tomography, magnetic resonance imaging, and positron emission tomography, among others) are routinely used in clinics and present their own advantages and limitations. In vivo near-infrared (NIR) fluorescence imaging has recently emerged as an attractive imaging modality combining low cost, high sensitivity, and relative safety. As a preclinical tool, it can be used to investigate disease mechanisms and for testing novel diagnostics and therapeutics prior to their clinical use. However, the limited depth of tissue penetration is a major challenge to efficient clinical use. Therefore, the current clinical use of fluorescence imaging is limited to a few applications such as image-guided surgery on tumors and retinal angiography, using FDA-approved dyes. Progress in fluorophore development and NIR imaging technologies holds promise to extend their clinical application to oncology, cardiovascular diseases, plastic surgery, and brain imaging, among others. Nanotechnology is expected to revolutionize diagnostic in vivo fluorescence imaging through targeted delivery of NIR fluorescent probes using antibody conjugation. In this review, we discuss the latest advances in in vivo fluorescence imaging technologies, NIR fluorescent probes, and current and future clinical applications.
Graphical Abstract
Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament
Authors: Tang Yifan , Sun Yanqing , Zeng Junkai , Yuan Bo , Zhao Yin , Geng Xiangwu , Jia Lianshun , Zhou Shengyuan , Chen Xiongsheng 
Published: October 2022

Abstract
Background
Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL.

Results
Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry.

Conclusions
We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.
TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer
Authors: Chen Libin , Xue Wang , Cao Jing , Zhang Shengmin , Zeng Yiqing , Ma Ling , Qian Xuechen , Wen Qing , Hong Yurong , Shi Zhan , Xu Youfeng 
Published: October 2022

Abstract
Background
Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells.

Results
Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors.

Conclusion
TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.
Antigenic molecular mimicry in viral-mediated protection from cancer: the HIV case
Authors: Manolio Carmen , Ragone Concetta , Cavalluzzo Beatrice , Mauriello Angela , Tornesello Maria Lina , Buonaguro Franco M. , Salomone Megna Angelo , D’Alessio Giovanna , Penta Roberta , Tagliamonte Maria , Buonaguro Luigi 
Published: October 2022

Abstract
Background
People living with HIV/AIDS (PLWHA) show a reduced incidence for three cancer types, namely breast, prostate and colon cancers. In the present study, we assessed whether a molecular mimicry between HIV epitopes and tumor associated antigens and, consequently, a T cell cross-reactivity could provide an explanation for such an epidemiological evidence.

Methods
Homology between published TAAs and non-self HIV-derived epitopes have been assessed by BLAST homology. Structural analyses have been performed by bioinformatics tools. Immunological validation of CD8+ T cell cross-reactivity has been evaluated ex vivo by tetramer staining.

Findings
Sequence homologies between multiple TAAs and HIV epitopes have been found. High structural similarities between the paired TAAs and HIV epitopes as well as comparable patterns of contact with HLA and TCR α and β chains have been observed. Furthermore, cross-reacting CD8+ T cells have been identified.

Interpretation
This is the first study showing a molecular mimicry between HIV antigens an TAAs identified in breast, prostate and colon cancers. Therefore, it is highly reasonable that memory CD8+ T cells elicited during the HIV infection may play a key role in controlling development and progression of such cancers in the PLWHA lifetime. This represents the first demonstration ever that a viral infection may induce a natural “preventive” anti-cancer memory T cells, with highly relevant implications beyond the HIV infection.
Radiomics features for assessing tumor-infiltrating lymphocytes correlate with molecular traits of triple-negative breast cancer
Authors: Su Guan-Hua , Xiao Yi , Jiang Lin , Zheng Ren-Cheng , Wang He , Chen Yan , Gu Ya-Jia , You Chao , Shao Zhi-Ming 
Published: October 2022

Abstract
Background
Tumor-infiltrating lymphocytes (TILs) have become a promising biomarker for assessing tumor immune microenvironment and predicting immunotherapy response. However, the assessment of TILs relies on invasive pathological slides.

Methods
We retrospectively extracted radiomics features from magnetic resonance imaging (MRI) to develop a radiomic cohort of triple-negative breast cancer (TNBC) (n = 139), among which 116 patients underwent transcriptomic sequencing. This radiomic cohort was randomly divided into the training cohort (n = 98) and validation cohort (n = 41) to develop radiomic signatures to predict the level of TILs through a non-invasive method. Pathologically evaluated TILs in the H&E sections were set as the gold standard. Elastic net and logistic regression were utilized to perform radiomics feature selection and model training, respectively. Transcriptomics was utilized to infer the detailed composition of the tumor microenvironment and to validate the radiomic signatures.

Results
We selected three radiomics features to develop a TILs-predicting radiomics model, which performed well in the validation cohort (AUC 0.790, 95% confidence interval (CI) 0.638–0.943). Further investigation with transcriptomics verified that tumors with high TILs predicted by radiomics (Rad-TILs) presented activated immune-related pathways, such as antigen processing and presentation, and immune checkpoints pathways. In addition, a hot immune microenvironment, including upregulated T cell infiltration gene signatures, cytokines, costimulators and major histocompatibility complexes (MHCs), as well as more CD8+ T cells, follicular helper T cells and memory B cells, was found in high Rad-TILs tumors.

Conclusions
Our study demonstrated the feasibility of radiomics model in predicting TILs status and provided a method to make the features interpretable, which will pave the way toward precision medicine for TNBC.
Prediction of osteoporosis and osteopenia by routine computed tomography of the lumbar spine in different regions of interest
Authors: Yang Guangyue , Wang Hansong , Wu Zhufeng , Shi Yinyu , Zhao Yongfang 
Published: October 2022

Abstract
Background
We aimed to investigate the utility of Hounsfield units (HU) obtained from different regions of interest in opportunistic lumbar computed tomography (CT) to predict osteoporosis coupling with data of dual-energy X-ray absorptiometry (DXA).

Methods
A total of 100 patients who attended a university hospital in Shanghai, China, and had undergone CT and DXA tests of the lumbar spine within 3 months were included in this retrospective review. Images were reviewed on axial sections, and regions of interest (ROI) markers were placed on the round, oval, anterior, left, and right of the L1–L4 vertebra to measure the HU. The mean values of CT HU were then compared to the bone mineral density (BMD) measured by DXA. Receiver operator characteristic curves were generated to determine the threshold for diagnosis and its sensitivity and specificity values.

Results
The differences in CT HU of different ROI based on DXA definitions of osteoporosis, osteopenia, and normal individuals were statistically significant (p < 0.01). The HU values of the different ROI correlated well with the BMD values (Spearman coefficient all > 0.75, p < 0.01). The threshold for diagnosing osteoporosis varies from 87 to 111 HU in different ROIs, and the threshold for excluding osteoporosis or osteopenia is 99–125 HU.

Conclusion
This is the first study on osteoporosis diagnosis of different ROI with routine CT lumbar scans. There is a strong correlation between CT HU of different ROI in the lumbar spine and BMD, and HU measurements can be used to predict osteoporosis.
The relationship between glycated hemoglobin A1c levels and exacerbation status in the patients with chronic obstructive pulmonary disease
Authors: Motamed Behrang , Alavi Foumani Ali , Tangestaninezhad Azita , Almasi Mohammad , Faraji Niloofar , Jafarinezhad Alireza 
Published: October 2022

Abstract
Objective
This study was performed in Razi Hospital, Rasht, Iran, between March 2016 and August 2018 on a population of chronic obstructive pulmonary disease (COPD) patients (56 as COPD exacerbation group and 56 as COPD stable group). Study variables include age, sex, occupation, body mass index (BMI), cigarette consumption, duration of COPD, annual hospitalization, dyspnea, glycated hemoglobin (HbA1c), FEV1, and FEV1/FVC indices.

Result
The mean age of the participants was 63.92 ± 10.75 years. There was a significant difference in the hospitalization between the patients with both exacerbation and normal state of COPD (P ≤ 0.001). HbA1c in the patients with exacerbation of COPD was significantly higher than stable status (P = 0.001). Logistic regression showed that HbA1c levels and hospitalization were predictors of exacerbation of COPD. HbA1c levels were statistically significant in terms of hospitalization in patients with COPD exacerbation. There was a significant difference between the HbA1c levels and MMRC in patients with COPD. The percentage of HbA1c was associated with exacerbation of COPD and HbA1c is a good predictor of disease severity in patients with COPD. It also shows that patients with COPD exacerbation and severe COPD are at the higher risk of hyperglycemia.
Characterisation of ethnic differences in DNA methylation between UK-resident South Asians and Europeans
Authors: Elliott Hannah R. , Burrows Kimberley , Min Josine L. , Tillin Therese , Mason Dan , Wright John , Santorelli Gillian , Davey Smith George , Lawlor Deborah A. , Hughes Alun D. , Chaturvedi Nishi , Relton Caroline L. 
Published: October 2022

AbstractEthnic differences in non-communicable disease risk have been described between individuals of South Asian and European ethnicity that are only partially explained by genetics and other known risk factors. DNA methylation is one underexplored mechanism that may explain differences in disease risk. Currently, there is little knowledge of how DNA methylation varies between South Asian and European ethnicities. This study characterised differences in blood DNA methylation between individuals of self-reported European and South Asian ethnicity from two UK-based cohorts: Southall and Brent Revisited and Born in Bradford. DNA methylation differences between ethnicities were widespread throughout the genome (n = 16,433 CpG sites, 3.4% sites tested). Specifically, 76% of associations were attributable to ethnic differences in cell composition with fewer effects attributable to smoking and genetic variation. Ethnicity-associated CpG sites were enriched for EWAS Catalog phenotypes including metabolites. This work highlights the need to consider ethnic diversity in epigenetic research.
Syrian females with congenital adrenal hyperplasia: a case series
Authors: Dehneh Nada , Jarjour Rami , Idelbi Sahar , Alibrahem Assad , Al Fahoum Sahar 
Published: October 2022

Abstract
Background
One of the most common types of congenital adrenal hyperplasia is an autosomal recessive disorder with 21-hydroxylase deficiency. The classical form, defined by cortisol insufficiency, is accompanied by prenatal androgen excess causing variable masculinization degrees of external genitalia in babies with a 46, XX karyotype.

Cases presentation
These five case reports highlight the management of Syrian females aged between 0 and 32 years with congenital adrenal hyperplasia. Two of the patients have been raised as males, while two had reconstructive surgery and one had hormonal therapy. Becoming mother was achieved by two patients

Conclusion
The integrated treatment of females with classical congenital adrenal hyperplasia CAH, which includes appropriate surgical procedures and controlled hormonal therapy, gives these females the opportunity to live as they are, and perhaps as mothers in the future.