bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA ACTA2-AS1 suppress colon adenocarcinoma progression by sponging miR-4428 upregulation BCL2L11
Authors: Pan Qingyun , Huang Ying , Wang Yirui , Li Deke , Lei Changjiang 
Published: April 2021

AbstractBackgroundLong non-coding RNA is considered to be essential to modulate the development and progression of human malignant cancers. And long non-coding RNA can act as crucial modulators by sponging the corresponding microRNA in tumorigenesis. We aimed to elucidate the function of ACTA2-AS1 and its molecular mechanism in colon adenocarcinoma.Materials and methodsThe expression of ACTA2-AS1, miR-4428 andBCL2L11in colon adenocarcinoma tissues were detected via qRT-PCR. SW480 and HT29 cells were transfected with shRNA ACTA2-AS1, OE ACTA2-AS1, miRNA mimics of miR-4428, miR-4428 inhibitor, si-BCL2L11and over-expression of si-BCL2L11. Cell proliferation, colony formation and apoptosis were respectively assessed using CCK-8 assay, colony assay and flow cytometry. Luciferase reporter assay was performed to verify the targets of ACTA2-AS1 and miR-4428. Tumor subcutaneous xenograft mode was constructed to explore tumor growth in vivo.ResultsACTA2-AS1 was obviously downregulated in human colon adenocarcinoma tissues and colon adenocarcinoma cell lines. Silence or over-expression of ACTA2-AS1 promoted or inhibited cell proliferation and colony formation abilities, and regulated apoptosis. The silence of ACTA2-AS1 resulted in the decrease of Bax and increase of Bal2, while restored in OE ACTA2-AS1 group when compared with the control transfected cells. In addition, luciferase reporter assay revealed that ACTA2-AS1 interacted with miR-4428 and suppressed its expression. miR-4428 could bind to 3ʹ untranslated region ofBCL2L11and modulated the expression ofBCL2L11negatively. Knockdown of ACTA2-AS1 and over-expression ofBCL2L11reversed the biological function that ACTA2-AS1 mediated by knockdown ACTA2-AS1 alone.ConclusionOur data demonstrated that ACTA2-AS1 could suppress colon adenocarcinoma progression via sponging miR-4428 to regulateBCL2L11expression.
Aspartame and cancer – new evidence for causation
Authors: Landrigan Philip J. , Straif Kurt 
Published: April 2021

Abstract
Background
Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women.
The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults.
These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms.

Methods
To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria.

Findings
This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection.

Interpretation
These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies.
These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.
Gender differences in risk factors for high plasma homocysteine levels based on a retrospective checkup cohort using a generalized estimating equation analysis
Authors: Zhao Jing , Li Zhihua , Hou Chengbei , Sun Fei , Dong Jing , Chu Xi , Guo Yansu 
Published: April 2021

Abstract
Background
Hyperhomocysteinemia (HHcy) is associated with various health problems, but less is known about the gender differences in risk factors for high plasma homocysteine (Hcy) levels.

Methods
In this study, a retrospective study was carried out on 14,911 participants (7838 males and 7073 females) aged 16–102 years who underwent routine checkups between January 2012 and December 2017 in the Health Management Department of Xuanwu Hospital, China. Anthropometric measurements, including body mass index (BMI) and waist-to-hip ratio, were collected. Fasting blood samples were collected to measure the biochemical indexes. The outcome variable was Hcy level, and a generalized estimating equation (GEE) analysis was used to identify the associations of interest based on gender.

Results
Males exhibited increased Hcy levels (16.37 ± 9.66 vs 11.22 ± 4.76 μmol/L) and prevalence of HHcy (37.0% vs 11.3%) compared with females. Hcy levels and HHcy prevalence increased with age in both genders, except for the 16- to 29-year-old group. GEE analysis indicated that irrespective of gender, aspartate aminotransferase, creatinine, uric acid, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were positively correlated with Hcy levels, and alanine aminotransferase, total cholesterol and glucose were negatively correlated with Hcy levels. However, age, BMI and triglycerides (TGs) were positively correlated with Hcy levels exclusively in females.

Conclusions
Gender differences in risk factors for high plasma Hcy levels were noted. Although common correlational factors existed in both genders, age, BMI and TGs were independent risk factors for Hcy levels specifically in females.
A benchmark for RNA-seq deconvolution analysis under dynamic testing environments
Authors: Jin Haijing , Liu Zhandong 
Published: April 2021

Abstract
Background
Deconvolution analyses have been widely used to track compositional alterations of cell types in gene expression data. Although a large number of novel methods have been developed, due to a lack of understanding of the effects of modeling assumptions and tuning parameters, it is challenging for researchers to select an optimal deconvolution method suitable for the targeted biological conditions.

Results
To systematically reveal the pitfalls and challenges of deconvolution analyses, we investigate the impact of several technical and biological factors including simulation model, quantification unit, component number, weight matrix, and unknown content by constructing three benchmarking frameworks. These frameworks cover comparative analysis of 11 popular deconvolution methods under 1766 conditions.

Conclusions
We provide new insights to researchers for future application, standardization, and development of deconvolution tools on RNA-seq data.
Effects of metformin withdrawal after long and short term treatment in PCOS: observational longitudinal study
Authors: Kravos Nika Aleksandra , Janež Andrej , Goričar Katja , Dolžan Vita , Jensterle Mojca 
Published: April 2021

AbstractBackgroundMetformin plays a consolidated role in the management of polycystic ovary syndrome (PCOS). However, there is no clear answer on how long we should treat and on how long its beneficial impact sustain after we stop treatment. We compared the effects of metformin withdrawal after long-term (LT) and short term (ST) treatment in PCOS women that had previously well responded to metformin.MethodsWe conducted observational longitudinal study including 44 PCOS women (31 (28–36) years and BMI 32.5 (27.7–34.9) kg/m2) that were followed for 6 months after metformin withdrawal. Prior inclusion, ST group had been treated with metformin on average for 1.03 ± 0.13 year, LT group for 5.07 ± 2.52 years. We followed anthropometric, metabolic, reproductive parameters and eating behavior as assessed by TFEQ-R18.ResultsAfter metformin withdrawal, ST group gained significant amount of weight (from 92 (75.5–107.3) kg to 96 (76–116) kg; p = 0.019). Weight tended to increase also in LT users (from 87 (75–103) to 87 (73–105) kg; p = 0.058). More women in LT group maintained stable weight (27% in LT group vs 15% in ST group). Eating behavior deteriorated in both groups. Withdrawal of metformin resulted in a decrease of menstrual frequency (6 (6–6) to 6 (4–6) menstrual bleeds per 6 months; p = 0.027) and in borderline increase of androstenedione (6.4 (4.6–7.6) to 7.8 (4.8–9.6) nmol/L; p = 0.053) in LT group. Waist circumference, HOMA and glucose homeostasis remained stable in both groups. There were no differences between groups at 6-month follow up.ConclusionCollectively, present study implies some metabolic and endocrine treatment legacy in both groups as well as some group-specific deteriorations in clinical parameters 6 months after metformin withdrawal.Trial registration: The study is registered at Clinical Trials with reference No. NCT04566718
Integrative study of EZH2 mutational status, copy number, protein expression and H3K27 trimethylation in AML/MDS patients
Authors: Stomper Julia , Meier Ruth , Ma Tobias , Pfeifer Dietmar , Ihorst Gabriele , Blagitko-Dorfs Nadja , Greve Gabriele , Zimmer Dennis , Platzbecker Uwe , Hagemeijer Anne , Schmitt-Graeff Ingrid , Lübbert Michael 
Published: April 2021

Abstract
Background
Mutations in the EZH2 gene are recurrently found in patients with myeloid neoplasms and are associated with a poor prognosis. We aimed to characterize genetic and epigenetic alterations of EZH2 in 58 patients (51 with acute myeloid leukemia and 7 with myelodysplastic or myeloproliferative neoplasms) by integrating data on EZH2 mutational status, co-occurring mutations, and EZH2 copy number status with EZH2 protein expression, histone H3K27 trimethylation, and EZH2 promoter methylation.

Results
EZH2 was mutated in 6/51 acute myeloid leukemia patients (12%) and 7/7 patients with other myeloid neoplasms. EZH2 mutations were not overrepresented in patients with chromosome 7q deletions or losses. In acute myeloid leukemia patients, EZH2 mutations frequently co-occurred with CEBPA (67%), ASXL1 (50%), TET2 and RAD21 mutations (33% each). In EZH2-mutated patients with myelodysplastic or myeloproliferative neoplasms, the most common co-mutations were in ASXL1 (100%), NRAS, RUNX1, and STAG2 (29% each). EZH2 mutations were associated with a significant decrease in EZH2 expression (p = 0.0002), which was similar in patients with chromosome 7 aberrations and patients with intact chromosome 7. An association between EZH2 protein expression and H3K27 trimethylation was observed in EZH2-unmutated patients (R2 = 0.2, p = 0.01). The monoallelic state of EZH2 was not associated with EZH2 promoter hypermethylation. In multivariable analyses, EZH2 mutations were associated with a trend towards an increased risk of death (hazard ratio 2.51 [95% confidence interval 0.87–7.25], p = 0.09); similarly, low EZH2 expression was associated with elevated risk (hazard ratio 2.54 [95% confidence interval 1.07–6.04], p = 0.04).

Conclusions
Perturbations of EZH2 activity in AML/MDS occur on different, genetic and non-genetic levels. Both low EZH2 protein expression and, by trend, EZH2 gene mutations predicted inferior overall survival of AML patients receiving standard chemotherapy.
Isolation and characterisation of ΦcrAss002, a crAss-like phage from the human gut that infects Bacteroides xylanisolvens
Authors: Guerin Emma , Shkoporov Andrey N. , Stockdale Stephen R. , Comas Joan Colom , Khokhlova Ekaterina V. , Clooney Adam G. , Daly Karen M. , Draper Lorraine A. , Stephens Niamh , Scholz Dimitri , Ross R. Paul , Hill Colin 
Published: April 2021

AbstractBackgroundThe gut phageome comprises a complex phage community of thousands of individual strains, with a few highly abundant bacteriophages. CrAss-like phages, which infect bacteria of the order Bacteroidales, are the most abundant bacteriophage family in the human gut and make an important contribution to an individual’s core virome. Based on metagenomic data, crAss-like phages form a family, with four sub-families and ten candidate genera. To date, only three representatives isolated in pure culture have been reported: ΦcrAss001 and two closely related phages DAC15 and DAC17; all are members of the less abundant candidate genus VI. The persistence at high levels of both crAss-like phage and their Bacteroidales hosts in the human gut has not been explained mechanistically, and this phage-host relationship can only be properly studied with isolated phage-host pairs from as many genera as possible.ResultsFaeces from a healthy donor with high levels of crAss-like phage was used to initiate a faecal fermentation in a chemostat, with selected antibiotics chosen to inhibit rapidly growing bacteria and selectively enrich for Gram-negative Bacteroidales. This had the objective of promoting the simultaneous expansion of crAss-like phages on their native hosts. The levels of seven different crAss-like phages expanded during the fermentation, indicating that their hosts were also present in the fermenter. The enriched supernatant was then tested against individual Bacteroidales strains isolated from the same faecal sample. This resulted in the isolation of a previously uncharacterised crAss-like phage of candidate genus IV of the proposed Alphacrassvirinae sub-family, ΦcrAss002, that infects the gut commensalBacteroides xylanisolvens. ΦcrAss002 does not form plaques or spots on lawns of sensitive cells, nor does it lyse liquid cultures, even at high titres. In keeping with the co-abundance of phage and host in the human gut, ΦcrAss002 andBacteroides xylanisolvenscan also co-exist at high levels when co-cultured in laboratory media.ConclusionsWe report the isolation and characterisation of ΦcrAss002, the first representative of the proposed Alphacrassvirinae sub-family of crAss-like phages. ΦcrAss002 cannot form plaques or spots on bacterial lawns but can co-exist with its host,Bacteroides xylanisolvens, at very high levels in liquid culture without impacting on bacterial numbers.
Niche partitioning in the Rimicaris exoculata holobiont: the case of the first symbiotic Zetaproteobacteria
Authors: Cambon-Bonavita Marie-Anne , Aubé Johanne , Cueff-Gauchard Valérie , Reveillaud Julie 
Published: April 2021

AbstractBackgroundFree-living and symbiotic chemosynthetic microbial communities support primary production and higher trophic levels in deep-sea hydrothermal vents. The shrimpRimicaris exoculata, which dominates animal communities along the Mid-Atlantic Ridge, houses a complex bacterial community in its enlarged cephalothorax. The dominant bacteria present are from the taxonomic groupsCampylobacteria,Desulfobulbia(formerlyDeltaproteobacteria),Alphaproteobacteria,Gammaproteobacteria, and some recently discovered iron oxyhydroxide-coatedZetaproteobacteria. This epibiotic consortium uses iron, sulfide, methane, and hydrogen as energy sources. Here, we generated shotgun metagenomes fromRimicaris exoculatacephalothoracic epibiotic communities to reconstruct and investigate symbiotic genomes. We collected specimens from three geochemically contrasted vent fields, TAG, Rainbow, and Snake Pit, to unravel the specificity, variability, and adaptation ofRimicaris–microbe associations.ResultsOur data enabled us to reconstruct 49 metagenome-assembled genomes (MAGs) from the TAG and Rainbow vent fields, including 16 with more than 90% completion and less than 5% contamination based on single copy core genes. These MAGs belonged to the dominantCampylobacteria,Desulfobulbia,Thiotrichaceae, and some novel candidate phyla radiation (CPR) lineages. In addition, most importantly, two MAGs in our collection were affiliated toZetaproteobacteriaand had no close relatives (average nucleotide identity ANI < 77% with the closest relativeGhiorsea bivoraisolated from TAG, and 88% with each other), suggesting potential novel species. Genes for Calvin-Benson Bassham (CBB) carbon fixation, iron, and sulfur oxidation, as well as nitrate reduction, occurred in both MAGs. However, genes for hydrogen oxidation and multicopper oxidases occurred in one MAG only, suggesting shared and specific potential functions for these two novelZetaproteobacteriasymbiotic lineages. Overall, we observed highly similar symbionts co-existing in a single shrimp at both the basaltic TAG and ultramafic Rainbow vent sites. Nevertheless, further examination of the seeming functional redundancy among these epibionts revealed important differences.ConclusionThese data highlight microniche partitioning in theRimicarisholobiont and support recent studies showing that functional diversity enables multiple symbiont strains to coexist in animals colonizing hydrothermal vents.
Risk factors for developing severe COVID-19 in China: an analysis of disease surveillance data
Authors: Geng Meng-Jie , Wang Li-Ping , Ren Xiang , Yu Jian-Xing , Chang Zhao-Rui , Zheng Can-Jun , An Zhi-Jie , Li Yu , Yang Xiao-Kun , Zhao Hong-Ting , Li Zhong-Jie , He Guang-Xue , Feng Zi-Jian 
Published: April 2021

Abstract
Background
COVID-19 has posed an enormous threat to public health around the world. Some severe and critical cases have bad prognoses and high case fatality rates, unraveling risk factors for severe COVID-19 are of significance for predicting and preventing illness progression, and reducing case fatality rates. Our study focused on analyzing characteristics of COVID-19 cases and exploring risk factors for developing severe COVID-19.

Methods
The data for this study was disease surveillance data on symptomatic cases of COVID-19 reported from 30 provinces in China between January 19 and March 9, 2020, which included demographics, dates of symptom onset, clinical manifestations at the time of diagnosis, laboratory findings, radiographic findings, underlying disease history, and exposure history. We grouped mild and moderate cases together as non-severe cases and categorized severe and critical cases together as severe cases. We compared characteristics of severe cases and non-severe cases of COVID-19 and explored risk factors for severity.

Results
The total number of cases were 12 647 with age from less than 1 year old to 99 years old. The severe cases were 1662 (13.1%), the median age of severe cases was 57 years [Inter-quartile range(IQR): 46–68] and the median age of non-severe cases was 43 years (IQR: 32–54). The risk factors for severe COVID-19 were being male [adjusted odds ratio (aOR) = 1.3, 95% CI: 1.2–1.5]; fever (aOR = 2.3, 95% CI: 2.0–2.7), cough (aOR = 1.4, 95% CI: 1.2–1.6), fatigue (aOR = 1.3, 95% CI: 1.2–1.5), and chronic kidney disease (aOR = 2.5, 95% CI: 1.4–4.6), hypertension (aOR = 1.5, 95% CI: 1.2–1.8) and diabetes (aOR = 1.96, 95% CI: 1.6–2.4). With the increase of age, risk for the severity was gradually higher [20–39 years (aOR = 3.9, 95% CI: 1.8–8.4), 40–59 years (aOR = 7.6, 95% CI: 3.6–16.3), ≥ 60 years (aOR = 20.4, 95% CI: 9.5–43.7)], and longer time from symtem onset to diagnosis [3–5 days (aOR = 1.4, 95% CI: 1.2–1.7), 6–8 days (aOR = 1.8, 95% CI: 1.5–2.1), ≥ 9 days(aOR = 1.9, 95% CI: 1.6–2.3)].

Conclusions
Our study showed the risk factors for developing severe COVID-19 with large sample size, which included being male, older age, fever, cough, fatigue, delayed diagnosis, hypertension, diabetes, chronic kidney diasease. Based on these factors, the severity of COVID-19 cases can be predicted. So cases with these risk factors should be paid more attention to prevent severity.
Distribution and factors associated with urogenital schistosomiasis in the Tiko Health District, a semi-urban setting, South West Region, Cameroon
Authors: Green Adeline Enjema , Anchang-Kimbi Judith Kuoh , Wepnje Godlove Bunda , Ndassi Vicky Daonyle , Kimbi Helen Kuokuo 
Published: April 2021

Abstract
Background
Increased risk of schistosomiasis in peri-urban and urban towns is not uncommon. An epidemiological survey was carried out in the Tiko Health District (THD), an unmapped transmission focus for urogenital schistosomiasis (UGS), to assess the distribution, intensity, and risk factors associated with the occurrence of UGS.

Methods
In this cross-sectional survey, 12 communities were purposively selected from four health areas (HAs) (Likomba, Holforth, Holforth-Likomba, and Mutengene) in South West Region of Cameroon between June and August 2018. Consenting individuals were enrolled using a convenient sampling technique and administered a semi-structured questionnaire to document information on socio-demographic and water contact behaviour. Urine samples were examined for Schistosomahaematobium infection using test strip, filtration, and microscopy methods. Bivariate and binary logistic regression analyses were used to identify predictors of infection.

Results
The overall prevalence of UGS in Likomba, Holforth-Likomba and Holforth was 31.5% [95% confidence interval (CI): 28.3–34.8] with geometric mean (GM) egg count of 28.7 (range: 2–450) eggs per 10 ml of urine. S.haematobium infection was not found in Mutengene HA. Infection was unevenly distributed among the HAs, Holforth-Likomba and Holforth being the most and least affected, respectively. The prevalence of infection varied (P < 0.001) among the affected communities, ranging from 12.0 to 56.9%. Infection status of the community related positively (P < 0.001) with proximity to stream (< 100 m), the degree of contact with water and number of improved water sources. Younger age group (5–14 years) [adjusted odds ratio (aOR): 3.7, 95% CI: 1.1–12.2] and intense water contact (degree II) (aOR: 5.2, 95% CI: 3.4–8.1) were associated with increased risk of infection. Similarly, significantly higher egg load was observed among younger aged groups (P = 0.02) and those who carried out intense water contact activities (P < 0.001).

Conclusions
Generally, THD is a moderate risk endemic focus for UGS but prevalence higher than 50.0% was observed in some communities. These findings warrant immediate mass chemotherapy with praziquantel to reduce morbidity. Provision of portable water and health education are proposed measures to reduce and eventually eliminate transmission in the area.

Graphic abstract
Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China
Authors: Adi Dilare , Abuzhalihan Jialin , Tao Jing , Wu Yun , Wang Ying-Hong , Liu Fen , Yang Yi-Ning , Ma Xiang , Li Xiao-Mei , Xie Xiang , Fu Zhen-Yan , Ma Yi-Tong 
Published: April 2021

Abstract
Background
Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang.

Methods
We designed two independent case–control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene.

Results
Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively).

Conclusions
The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.