bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis
Authors: Agudiez Marta , Martinez Paula J. , Martin-Lorenzo Marta , Heredero Angeles , Santiago-Hernandez Aranzazu , Molero Dolores , Garcia-Segura Juan Manuel , Aldamiz-Echevarria Gonzalo , Alvarez-Llamas Gloria 
Published: December 2020

Abstract
Background
Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk.

Results
Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated.
Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes.

Conclusions
We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.
Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development
Authors: Hu Junhe , Dong Jinyi , Zeng Zhi , Wu Juan , Tan Xiansheng , Tang Tao , Yan Jiao , Jin Chenzhong 
Published: December 2020

Abstracts
Background
Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section.

Results
First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions.

Conclusions
Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.
Airway regulatory T cells are decreased in COPD with a rapid decline in lung function
Authors: Eriksson Ström Jonas , Pourazar Jamshid , Linder Robert , Blomberg Anders , Lindberg Anne , Bucht Anders , Behndig Annelie F. 
Published: December 2020

Abstract
Background
Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1.

Methods
Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

Results
The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function.

Conclusions
COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1.
Trial registration Clinicaltrials.gov identifier NCT02729220
High expression level of serpin peptidase inhibitor clade E member 2 is associated with poor prognosis in lung adenocarcinoma
Authors: Dokuni Ryota , Nagano Tatsuya , Jimbo Naoe , Sato Hiroki , Kiriu Tatsunori , Yasuda Yuichiro , Yamamoto Masatsugu , Tachihara Motoko , Kobayashi Kazuyuki , Maniwa Yoshimasa , Nishimura Yoshihiro 
Published: December 2020

Abstract
Background
Recent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in lung adenocarcinomas are still unknown.

Methods
The expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Cell number assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells.

Results
The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells

Conclusion
These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.
Associations between ultraviolet radiation, tree cover and adolescent sunburns
Authors: Tribby Calvin P. , Julian Anne K. , Oh April Y. , Perna Frank M. , Berrigan David 
Published: December 2020

Abstract
Background
Sunburn is the strongest risk factor for melanoma and non-melanoma skin cancers. Adolescent sunburns are related to higher risk of developing melanoma later in life. Little is known about the association of sunburns and shade, particularly tree cover, around adolescent homes and schools. This linkage study assessed associations of adolescent self-reported sunburns with ambient ultraviolet radiation (UV) and tree cover.

Methods
We analyzed a U.S. national sample of parent–child dyads (n = 1333) from the 2014 Family Life, Activity, Sun, Health, and Eating (FLASHE) study conducted by the National Cancer Institute. The outcome was adolescent sunburns reported for the previous 12 months. GIS buffers around geocoded home and school addresses were used to summarize UV and tree cover. A sensitivity analysis assessed different UV measures and tree cover buffer distances. Logistic regression models estimated the adjusted odds of any sunburns for five models: (1) no environmental variables; (2) spatial variables of latitude and longitude; (3) UV; (4) tree cover; and, (5) a combined model with UV and tree cover. Covariates included common sunburn-related items such as sun protective behaviors, socio-demographics, and latitude. Model residuals were assessed for spatial dependency and clustering.

Results
Overall, 44% of adolescents reported any sunburns in the previous 12 months. For the bivariate associations, lower categories of UV were associated with any reported sunburns (p-trend = 0.002). Home tree cover was not associated with any reported sunburns (p-trend = 0.08), whereas schools with lower categories of tree cover were associated with sunburns (p-trend = 0.008). The adjusted odds of any sunburns by UV tertiles, as a linear tread, was 0.89 (0.76–1.05) (p = 0.17); school tree cover was: 0.91 (0.78–1.07) (p = 0.25). Neither UV nor tree cover, in a combined model, were significant. Sensitivity analyses resulted in the optimal buffer size of 200 m for summarizing tree cover. Spatial dependence of residuals was not significant and clustering was significant for about 6% or less of the sample in each model.

Conclusions
We did not find significant relationships between UV or tree cover and adolescent sunburns, when adjusted by sunburn-related covariates. Better contextual data about where sunburns occurred is needed to identify environmental correlates of sunburn.
A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet
Authors: Suzuki-Kemuriyama Noriko , Abe Akari , Uno Kinuko , Ogawa Shuji , Watanabe Atsushi , Sano Ryuhei , Yuki Megumi , Miyajima Katsuhiro , Nakae Dai 
Published: December 2020

Abstract
Background
Nonalcoholic steatohepatitis (NASH) is a form of liver disease characterized by steatosis, necroinflammation, and fibrosis, resulting in cirrhosis and cancer. Efforts have focused on reducing the intake of trans fatty acids (TFAs) because of potential hazards to human health and the increased risk for NASH. However, the health benefits of reducing dietary TFAs have not been fully elucidated. Here, the effects of TFAs vs. a substitute on NASH induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet (CDAA-HF) were investigated.

Methods
Mice were fed CDAA-HF containing shortening with TFAs (CDAA-HF-T(+)), CDAA-HF containing shortening without TFAs (CDAA-HF-T(−)), or a control chow for 13 or 26 weeks.

Results
At week 13, NASH was induced in mice by feeding CDAA-HF-T(+) containing TFAs or CDAA-HF-T(−) containing no TFAs, but rather mostly saturated fatty acids (FAs), as evidenced by elevated serum transaminase activity and liver changes, including steatosis, inflammation, and fibrosis. CDAA-HF-T(−) induced a greater extent of hepatocellular apoptosis at week 13. At week 26, proliferative (preneoplastic and non-neoplastic) nodular lesions were more pronounced in mice fed CDAA-HF-T(−) than CDAA-HF-T(+).

Conclusions
Replacement of dietary TFAs with a substitute promoted the development of proliferation lesions in the liver of a mouse NASH model, at least under the present conditions. Attention should be paid regarding use of TFA substitutes in foods for human consumption, and a balance of FAs is likely more important than the particular types of FAs.
Factors associated with drug checking service utilization among people who use drugs in a Canadian setting
Authors: Long Viseth , Arredondo Jaime , Ti Lianping , Grant Cameron , DeBeck Kora , Milloy M-J , Lysyshyn Mark , Wood Evan , Kerr Thomas , Hayashi Kanna 
Published: December 2020

Abstract
Background
The United States and Canada are amidst an opioid overdose crisis, with the Canadian province of British Columbia (BC) among the hardest hit. In response, drug checking services (DCS) have been introduced in this setting as a novel pilot harm reduction intervention though little is known about usage rates. Therefore, we sought to identify factors associated with drug checking uptake among people who use drugs (PWUD) in Vancouver, BC.

Methods
Data were derived from three ongoing prospective cohort studies of PWUD in Vancouver between June and November 2018. Multivariable logistic regression was used to determine factors associated with self-reported DCS utilization in the past 6 months among participants at high risk of fentanyl exposure (i.e., those self-reporting illicit opioid use or testing positive for fentanyl via urine drug screen).

Results
Among 828 eligible participants, including 451 (55%) males, 176 (21%) reported recent use of DCS. In multivariable analyses, factors significantly associated with DCS utilization included: homelessness (Adjusted Odds Ratio [AOR] 1.47; 95% Confidence Interval [CI] 1.01–2.13) and involvement in drug dealing (AOR 1.59; 95% CI 1.05–2.39).

Conclusions
In our sample of PWUD, uptake of DCS was low, although those who were homeless, a sub-population known to be at a heightened risk of overdose, were more likely to use the services. Those involved in drug dealing were also more likely to use the services, which may imply potential for improving drug market safety. Further evaluation of drug checking is warranted.
Suspected heparin-induced thrombocytopenia in a COVID-19 patient on extracorporeal membrane oxygenation support: a case report
Authors: Phan Xuan T. , Nguyen Tuan H. , Tran Tung T. , Huynh Thu-Hien T. , Hoang Thuy-Ha T. , Nguyen Vinh-Chau V. , Pham Thao N. T. 
Published: December 2020

AbstractBackgroundExtracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage.Case presentationIn this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery.ConclusionHIT may jeopardize patient’s care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.
Macroeconomic, demographic and human developmental correlates of physical activity and sitting time among South American adults
Authors:   on behalf of the South American Physical Activity and Sedentary Behavior Network (SAPASEN) collaborators, Werneck André O. , Sadarangani Kabir P. , Ramírez-Vélez Robinson , Baldew Se-Sergio , Gomes Thayse N. , Ferrari Gerson , Szwarcwald Célia L. , Miranda J. Jaime , Silva Danilo R. 
Published: December 2020

Abstract
Background
Our aim was to investigate the association of macroeconomic, human development, and demographic factors with different domains of physical activity and sitting time among South American adults.

Methods
We used data from nationally representative samples in Argentina (n = 26,932), Brazil (n = 52,490), Chile (n = 3866), Colombia (n = 14,208), Ecuador (n = 19,883), Peru (n = 8820), and Uruguay (n = 2403). Our outcomes included leisure time (≥150 min/week), transport (≥10 min/week), occupational (≥10 min/week), and total (≥150 min/week) physical activity, as well as sitting time (≥4 h/day), which were collected through self-reported questionnaires. As exposures, gross domestic product, total population, population density, and human development index indicators from the most updated national census of each country were used. Age and education were used as covariates. Multilevel logistic regressions with harmonized random effect meta-analyses were conducted, comparing highest vs. lowest (reference) tertiles.

Results
Higher odds for transport physical activity were observed among the highest tertiles of total population (ORmen: 1.41; 95% CI: 1.23–1.62), ORwomen: 1.51; 95% CI:1.32–1.73), population density (ORmen: 1.36; 95% CI: 1.18–1.57, ORwomen: 1.49; 95% CI: 1.30–1.70), and gross domestic product (ORmen: 1.16; 95% CI: 1.00–1.35, ORwomen: 1.39; 95% CI: 1.20–1.61). For leisure physical activity, women living in departments with higher human development index presented 18% higher odds for being active, and for total physical activity a similar estimate in both sexes was observed among those who live in more populated areas. No consistent associations were found for occupational physical activity and sitting time.

Conclusion
Macroeconomic, demographic and human development indicators are associated with different domains of physical activity in the South American context, which can in turn guide policies to promote physical activity in the region.
Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases
Authors: Biechele Gloria , Franzmeier Nicolai , Blume Tanja , Ewers Michael , Luque Jose Medina , Eckenweber Florian , Sacher Christian , Beyer Leonie , Ruch-Rubinstein Francois , Lindner Simon , Gildehaus Franz-Josef , von Ungern-Sternberg Barbara , Cumming Paul , Bartenstein Peter , Rominger Axel , Höglinger Günter U. , Herms Jochen , Brendel Matthias 
Published: December 2020

Abstract
Background
In vivo assessment of neuroinflammation by 18-kDa translocator protein positron-emission-tomography (TSPO-PET) ligands receives growing interest in preclinical and clinical research of neurodegenerative disorders. Higher TSPO-PET binding as a surrogate for microglial activation in females has been reported for cognitively normal humans, but such effects have not yet been evaluated in rodent models of neurodegeneration and their controls. Thus, we aimed to investigate the impact of sex on microglial activation in amyloid and tau mouse models and wild-type controls.

Methods
TSPO-PET (18F-GE-180) data of C57Bl/6 (wild-type), AppNL-G-F (β-amyloid model), and P301S (tau model) mice was assessed longitudinally between 2 and 12 months of age. The AppNL-G-F group also underwent longitudinal β-amyloid-PET imaging (Aβ-PET; 18F-florbetaben). PET results were confirmed and validated by immunohistochemical investigation of microglial (Iba-1, CD68), astrocytic (GFAP), and tau (AT8) markers. Findings in cerebral cortex were compared by sex using linear mixed models for PET data and analysis of variance for immunohistochemistry.

Results
Wild-type mice showed an increased TSPO-PET signal over time (female +23%, male +4%), with a significant sex × age interaction (T = − 4.171, p < 0.001). The Aβ model AppNL-G-F mice also showed a significant sex × age interaction (T = − 2.953, p = 0.0048), where cortical TSPO-PET values increased by 31% in female AppNL-G-F mice, versus only 6% in the male mice group from 2.5 to 10 months of age. Immunohistochemistry for the microglial markers Iba-1 and CD68 confirmed the TSPO-PET findings in male and female mice aged 10 months. Aβ-PET in the same AppNL-G-F mice indicated no significant sex × age interaction (T = 0.425, p = 0.673). The P301S tau model showed strong cortical increases of TSPO-PET from 2 to 8.5 months of age (female + 32%, male + 36%), without any significant sex × age interaction (T = − 0.671, p = 0.504), and no sex differences in Iba-1, CD68, or AT8 immunohistochemistry.

Conclusion
Female mice indicate sex-dependent microglia activation in aging and in response to amyloidosis but not in response to tau pathology. This calls for consideration of sex difference in TSPO-PET studies of microglial activation in mouse models of neurodegeneration and by extension in human studies.
Association between SLC44A4-NOTCH4 SNPs and serum lipid levels in the Chinese Han and Maonan ethnic groups
Authors: Zheng Peng-Fei , Yin Rui-Xing , Guan Yao-Zong , Wei Bi-Liu , Liu Chun-Xiao , Deng Guo-Xiong 
Published: December 2020

AbstractBackgroundThe current research was to assess the relationship of the solute carrier family 44 member 4 (SLC44A4) rs577272, notch receptor 4 (NOTCH4) rs3134931 SNPs and serum lipid levels in the Han and Maonan ethnic groups.MethodsThe genetic makeup of theSLC44A4rs577272 andNOTCH4rs3134931 SNPs in 2467 unrelated subjects (Han, 1254; Maonan,1213) was obtained by using polymerase chain reaction and restriction fragment length polymorphism technique, combined with gel electrophoresis, and confirmed by direct sequencing.ResultsThe genotype frequencies ofSLC44A4rs577272 andNOTCH4rs3134931 SNPs were different between Han and Maonan populations (P < 0.05); respectively. TheSLC44A4rs577272 SNP was associated with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in Maonan group. TheNOTCH4rs3134931 SNP was associated with triglyceride (TG) in Han; and TG and low-density lipoprotein cholesterol (LDL-C) levels in Maonan groups (P < 0.025–0.001). Stratified analysis according to gender showed that theSLC44A4rs577272 SNP was associated with TC and HDL-C in Han and Maonan females; TC in Maonan males, meanwhile, theNOTCH4rs3134931 SNP was associated with TG and HDL-C in Han males; TG in Han females; TG and LDL-C in Maonan males; and TG, HDL-C and LDL-C in Maonan females. Linkage disequilibrium analysis showed that the most common haplotype was rs577272G-rs3134931A (> 50%) in both Han and Maonan groups. The haplotype of rs577272G-rs3134931A was associated with TG and HDL-C in Han; and TC, TG and HDL-C in Maonan ethnic groups.ConclusionsThese results suggest that the relationship amongSLC44A4rs577272,NOTCH4rs3134931 SNPs and serum lipid parameters may vary depending on the gender and/or ethnicity/race in some populations. Haplotypes could explain more changes in serum lipid parameters than any single SNP alone particularly for TC, TG and HDL-C.