bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly
Authors: Pegueroles Jordi , Pané Adriana , Vilaplana Eduard , Montal Víctor , Bejanin Alexandre , Videla Laura , Carmona-Iragui María , Barroeta Isabel , Ibarzábal Ainitze , Casajoana Anna , Alcolea Daniel , Valldeneu Silvia , Altuna Miren , de Hollanda Ana , Vidal Josep , Ortega Emilio , Osorio Ricardo , Convit Antonio , Blesa Rafael , Lleó Alberto , Fortea Juan , Jiménez Amanda 
Published: January 2020

Abstract
Background: Mid-life obesity is related to increased risk for overall dementia and Alzheimer´s disease (AD) dementia. In the present work, we aimed to investigate the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) biomarkers of amyloid (Aβ 1-42) and tau-pathology (total-tau and p-tau) in healthy elderly. Methods: We selected healthy controls from ADNI2 with available CSF AD biomarkers and/or fluorodeoxyglucose (FDG) PET and 3T-MRI. Participants without follow-up or with significant weight loss were excluded from the analyses. Brain cortical thickness (Cth) was evaluated with Freesurfer software and FDG uptake was measured with a surface-based method using both SPM and Freesurfer softwares. We performed regression analyses between FDG uptake, CTh, CSF AD biomarkers levels and BMI and interaction analyses with age by obesity/overweight status. Results: We included 147 individuals (mean age 73.3 years, mean BMI 27.4 Kg/m 2 ). Higher BMI was related to less cortical thickness and higher glucose metabolism in brain areas not typically involved in AD (FWE<0.05), with little overlap between them. There was no association between BMI and any of the CSF core AD biomarkers. The relationship between age and brain metabolism was modified by overweight/obesity status, but not that of age and brain structure or core CSF AD biomarkers. Conclusions: Our data support that obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology in cognitively unimpaired elderly.
Substance Use Identification and Follow-up Rates among Commercial and Medicare Health Insurance Members in Primary Care and Other Settings
Authors: Baker John G. , Doxbeck David R. , Washington Melanie E. , Horton Angela , Dunning Adam 
Published: January 2020

Abstract
Background The objective of this study was to investigate factors associated with substance abuse identification and follow-up rates among samples of members of a private health insurance plan. Methods In an observational study, samples of claims data for 2017 for Commercial and Medicare members from a private health insurer were accessed and analyzed using descriptive statistics, decision tree analysis, and linear regression models. Results Medicare members had higher rates of inclusion in a measure of substance abuse than Commercial members, lower rates of initial short term follow-up, more opioid prescriptions from primary care provides, fewer prescriptions for opioid treatment, and higher rates of selected comorbid conditions. Mental health diagnoses and substance use problems co-occurred frequently and to a greater extent in the Medicare sample. Among commercial members, there were primarily alcohol problems that increased with age, while opioid abuse at about 10% peaked in the mid-twenties. More males were included among all substance types. The overall rate for an initial short term follow-up visit indicating initiation of treatment was 30%. There were large differences in the follow-up rates across settings with a very low rate (4.6% for alcohol and 6.9% for opioids) in primary care settings. Conclusions These results suggest that increased attention in primary care to young adult males and to older adults, may help to reduce substance abuse rates, especially alcohol abuse.
Characterization of Ethanol Producing Yeasts for Their Efficiency in Ethanol production, Salt Tolerance, and Utilization of Glucose and Xylose
Authors: Joshi Jarina , Bhattarai Tribikram , Yadav Amar , Sreer Lakshmaiah 
Published: January 2020

Abstract
Yeasts are the mainstay in ethanol production industry. Search for efficient yeast strains that are salt tolerant and utilize both hexoses (glucose) and pentoses (xylose and arabinose) is important in fermentation industry. In this regard,12 yeast strains, viz., CDBT1-12, were isolated from various sources and characterized. Molecular characterization of the yeast strains was done by sequencing 26S rRNA gene, D1D2 region. Out of 12 isolates, 10 were found to be Saccharomyces cerevisiae , CDBT7 was Wikerhamomyces anomalous , and CDBT8 was Cyberlindnera fabianii . The yeast isolates were characterized in terms of their ethanol production efficiency, salt tolerance and ability to utilize of glucose and xylose. All the strains were found to be good ethanol producers. Yeast strain CDBT2 was found to have tolerance for high salt (up to 15%) and ethanol (up to 16%) concentrations. Yeast strain CDBT7 was found to utilize both glucose and xylose without compromising on ethanol production efficiency. The CDBT7 strain was also salt tolerant (up to15%).Yeast strain CDBT2 when grown in an electrochemical cell with low levels of applied external voltage, alcohol dehydrogenase (ADH1) and pyruvate decarboxylase (PDC1) mRNA levels were increased by 2.78 ± 0.80 and 1.12 ± 0.37 fold, respectively. We believe, the latter observation is novel and it has not been reported previously. It also further supports our previous observation of increase in level of alcohol production by CDBT2 strain in the presence of applied electrical current.
Early liver injury is closely related to organ failure of sepsis
Authors: Peng Milin , Ai Yuhang , Zhang Lina , Zhao Shuangping , Liu Zhiyong , Zhang Haisong , Zhang Xiaolei , Qi Desheng 
Published: January 2020

Abstract
Backgrounds: Sepsis induced organ failure is main cause of mortality in intensive care units (ICU), however, the impact of early liver injury on clinical ending of sepsis is not clear and has not been discussed in context of clinical research on sepsis before. Our study aimed at the investigation of the clinical effect of early liver injury within 48h at ICU admission on sepsis outcomes. Methods: A single-centered, retrospective cohort of 198 adult critical patients diagnosed with sepsis were included in different ICU departments of Xiangya hospital from 2016 to 2018. Patients were divided into two groups, early liver injury and non-early liver injury within 48h at ICU admission. Baseline characteristics, clinical outcomes and risk factors of these two groups were studied. Logistic regression analysis, Cox hazard analysis, Kaplan-Meier and log-rank test were used. Results: In total, 198 patients with sepsis were included, with 106 (53.5%) with early liver injury and overall in-hospital mortality was 45.9% (n=91). Compared to non-early liver injury group, patients with early liver injury had significant higher SOFA (7.44±3.83 vs. 5.55±2.61, P<0.001), APACHE II score (15.22±23.14 vs. 9.14±8.72, P=0.013) , procalcitonin (37.10±59.20 vs. 19.24±48.10, P=0.021) , and rate of shock (63.2% vs. 48.9%, P=0.046). Primary outcome showed that early liver injury group had significant higher rate of renal dysfunction (62.3 vs. 33.7%, P<0.001), coagulation (31.1% vs. 13.0%, P=0.004) and hematologic system (72.6% vs. 52.2%, P=0.003) dysfunction hinting at higher organ failure rate. Age (OR 0.966; 95% CI 0.944-0.989; P=0.004), hypertriglyceridemia (OR 1.636; 95% CI 1.049-2.551; P=0.030), serum total bile acid (TBA, OR 1.071; 95% CI 1.030-1.113; P=0.001), hemoglobin (OR 1.030; 95% CI 1.013-1.046; P<0.001) and renal dysfunction (OR 3.403; 95% CI 1.631-7.099; P=0.001) were the independent predictors for early liver injury in sepsis by multiple regression analysis. Kaplan-Meier survival analyze demonstrated early liver injury and non-early liver injury group had similar survival time. Conclusion: Early liver injury within 48 hours on ICU admission is closely related to organ failure for patients with sepsis. Future study with big data is required to verify our viewpoint.
Lyn inhibited BCR signal pathway mediates B-cell anergy induced by avian leukosis virus subgroup J
Authors: He Shuhai , Zheng Gaoying , Yang Xiaoxia , Dong Jianguo , Zhou Defang , Venugopal Nair , Yao Yongxiu , Cheng Ziqiang 
Published: January 2020

Abstract
Background: Immune tolerance induced by retrovirus is a prerequisite for tumorigeness. We had reported that B-cell anergy was the main reason for immune tolerance induced by avian leukosis virus subgroup J (ALV-J). However, the molecular mechanism remains unclear.
Results: Initially, we found that Lyn showed down-regulation in chick embryo fibroblasts (CEF) and up-regulation in B-cells infected by ALV-J. So, we speculated that tyrosine kinase Lyn plays a key role in B-cell anergy induced by ALV-J. Confocal laser scanning microscopy (CLSM) and co-immunoprecipitation (Co-IP) results demonstrated that ALV-J indirectly regulated the expression of Lyn. To further investigate the role and regulatory mechanism of Lyn in B-cell anergy induced by ALV-J, the expression levels of Lyn and Syk at different phosphorylation site, the Ca 2+ mobilization, and the expression levels of NF-κB p65 protein in vitro and vivo were detected in B-cells. The result showed that Ca 2+ mobilization was delayed and p65 expression level was decreased in B-cells after ALV-J infection. Consistently, the retrieve of Ca 2+ mobilization, expression levels of NF-κB p65 were found after RNA interference of Lyn. Subsequently, we demonstrated that the activation of phosphorylated Lyn protein at Tyr507 site played a critical role in B-cells anergy, which were verified by the fact of the significantly up-regulation of the expression levels of phosphorylated Syk protein at Tyr525/526 site when RNA interference for Lyn were performed in B-cells. Furthermore, immunohistochemical (IHC) staining results confirmed that the expression levels of Lyn phosphorylated protein at Tyr507 site in bursal cells were increased, while the expression levels of Syk phosphorylated protein at Tyr525/526 sites were decreased.
Conclusions: These findings suggested that Lyn inhibited BCR signal pathway mediates B-cell anergy under ALV-J infection，which will provide a new insight for revealing the molecular mechanism of immune tolerance induced by ALV-J.
Keywords: avian leukosis virus subgroup J , B-cell anergy, immune tolerance, Lyn, Syk
Incidence and risk factors of symptomatic knee osteoarthritis among the Chinese population: analysis from a nationwide longitudinal study
Authors: Ren Yan , Hu Jiang , Tan Jin , Tang Xiaoming , Li Qianrui , Yang Huazhen , Liu Chunrong , He Qiao , Zhou Kang , Sun Xin , Tan Bo 
Published: January 2020

Abstract
Background: To investigate the incidence of symptomatic knee osteoarthritis (OA) and identify risk factors among the Chinese population.

Methods: The China Health and Retirement Longitudinal Study (CHARLS) is a nationwide longitudinal survey of persons aged ≥45 years. The baseline survey for the CHARLS study was conducted in 2011 using a four-stage, stratified, cluster probability sampling design. The respondents were then followed up every 2 years through a face-to-face interview. Using the national survey data collected from the CHARLS, we estimated the incidence of symptomatic knee OA, taking into account the complex survey design and response rate. We applied weighted logistic regression analysis to identify risk factors.

Results: In the 4 years of follow-up, the cumulative incidence of symptomatic knee OA among middle-aged and older Chinese adults was 8.5%; the incidence was higher among females (11.2%) than males (5.6%). In the longitudinal analysis, female, rural area, West region, low education level, lack of physical activities, and the presence of heart disease, kidney disease, and digestive disease at the baseline survey were associated with a higher risk of symptomatic knee OA. The risk in persons doing regular physical activities was 53% lower than that in persons who were not active (odds ratio (OR) 0.47 [95% CI) 0.29–0.76]). Histories of heart disease (odds ratio (OR) 1.40 [95% confidence interval (CI) 1.07–1.82]), kidney disease (OR 1.80 [95% CI 1.35–2.39]), and digestive disease (OR 1.54 [95% CI 1.30–1.82]) were associated with a higher risk of symptomatic knee OA.

Conclusion: The cumulative incidence of symptomatic knee OA over 4 years was relatively high, and varied by province and region. Lack of physical activities, and the presence of heart disease, kidney disease, and digestive disease were associated with a higher risk of symptomatic knee OA.
Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: A nationwide study during 1985-2015.
Authors: Konstantinoudis Garyfallos , Schuhmacher Dominic , Ammann Roland A , Diesch Tamara , Kuehni Claudia E , Spycher Ben D 
Published: January 2020

Abstract
Background The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. We investigated the spatial variation of childhood cancers in Switzerland using exact geocodes of place of residence. Methods We included 5,947 children diagnosed with cancer during 1985-2015 at age 0-15 from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardization to adjust for age and year of diagnosis. We examined whether the modelled spatial variation of risk can be explained by ambient air concentration of NO 2 , natural background radiation, area-based socio-economic position (SEP), linguistic region, years of existing general cancer registration in the canton or degree of urbanization. Results For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for CNS tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was evidence of an association of background radiation and SEP with incidence of CNS tumours, (1.19;0.98-1.40) and (1.6;1-1.13) respectively. Conclusion Of the investigated diagnostic groups, childhood CNS tumours show the largest spatial variation in Switzerland. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role.
Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis
Authors: Wang Wei , Liu Bin , Duan Xiaoran , Feng Xiaolei , Wang Tuanwei , Wang Pengpeng , Ding Mingcui , Zhang Qiao , Feng Feifei , Wu Yongjun , Yao Wu , Wang Qi , Yang Yongli 
Published: January 2020

Objective:
The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of
lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms.

Methods:
The data for a total of 535 patients with LUAD data were downloaded from The Cancer
Genome Atlas (TCGA) database. The miRNAs for LUAD prognosis were screened by both Cox risk
proportional regression model and Last Absolute Shrinkage and Selection Operator (LASSO) regression
model. The performances of the models were verified by time-dependent Receiver Operating
Characteristic (ROC) curve. The possible biological processes linked to the miRNAs’ target genes were
analyzed by Gene Ontology (GO), Kyoto gene and genome encyclopedia (KEGG).

Results:
Among 127 differentially expressed miRNAs identified from the screening analysis, there are 111
up-regulated and 16 down-regulated miRNAs. Three of them, hsa-miR-1293, hsa-miR-490 and hsa-miR-
5571, were also significantly associated with the survival of the LUAD patients. The targets of the three
miRNAs are significantly enriched in systemic lupus erythematosus pathways.

Conclusion:
Hsa-miR-1293, hsa-miR-490 and hsa-miR-5571 can be potentially used as novel biomarkers
for the prognosis prediction of LUAD.
Synthesis and Biological Evaluation of Heterocyclic Substituted Bis(indolyl)methanes
Authors: Li Min-Xin , Pu Xiao-Jia , Zhang Xia , Zheng Xi , Gao Hui , Xiao Wei-Lie , Wan Chun-Ping , Mao Ze-Wei 
Published: January 2020

Background:
Bis(indolyl)methane derivatives are widely found in nature with a broad range of
biological and pharmacological activities. The development of techniques for the synthesis and
functionalization of bis(indolyl)methanes have attracted more and more attention in recent years.

Objective:
To study the synthesis and biological activity of heterocyclic substituted bis(indolyl)methanes.

Materials and Methods:
A series of heterocyclic substituted bis(indolyl)methanes (3a-3p) have been prepared
by condensation reaction of indole and heterocyclic aldehydes catalyzed by boron trifluoride etherate with high
yields. Preliminary in vitro anti-inflammatory in lipopolysaccharide (LPS)-stimulated RAW-264.7
macrophages and cytotoxic activity against human tumor cell lines (A549, Hela and SGC7901) by MTT assay
were tested.

Results:
The result indicated that heterocyclic substituted bis(indolyl)methanes showed good antiinflammatory
and selective cytotoxic activity. Especially, compounds 3o, 3p and 3q displayed similar
inhibitory effect on the generation of NO to positive control dexamethasone, and compound 3q displayed
similar selective cytotoxic activity to 5-FU.

Conclusion:
Heterocyclic substituted bis(indolyl)methanes may be used as potential anti-inflammatory and
anticancer leads.
Recent Progress Towards Synthesis of the Indolizidine Alkaloid 195B
Authors: Ziarani Ghodsi Mohammadi , Mohajer Fatemeh , kheilkordi Zohreh 
Published: January 2020

Background:
Natural products have been received attention due to their importance in human life as
those are biologically active. In this review, there are some reports through different methods related to the
synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature,
the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and
researchers.

Objective:
This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018
due to their importance as a natural product.

Conclusion:
There are several methods to give rise to the indolizidine 195B as a natural product that is highly
active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the
preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported
from different aromatic and aliphatic.
Quercetin Decreased Alveolar Bone Loss and Apoptosis in Experimentally Induced Periodontitis Model in Wistar Rats
Authors: Taskan Mehmet Murat , Gevrek Fikret 
Published: January 2020

Background:
Quercetin is a flavonoid which has potent anti-inflammatory, antibacterial,
and antioxidant effect. Purpose of this study was to evaluate effects of quercetin
on alveolar bone loss and histopathological changes in ligature-induced periodontitis in rats.

Methods:
Wistar rats were divided into four experimental groups: non-ligated control (C,
n=8) group; periodontitis (P, n=8) group; ligature and low dose quercetin group (75
mg/kg/day quercetin, Q75 group, n=8); ligature and high dose quercetin group (150
mg/kg/day quercetin, Q150 group, n=8). Silk ligatures were placed at gingival margin of
lower first molars of mandibular right quadrant. Study duration was 15 days, and animals
were sacrificed end of this period. Changes in alveolar bone levels were clinically measured
and tissues were immunohistochemically examined, matrix metalloproteinase 8
(MMP 8), inducible nitric oxide synthase (iNOS), tissue inhibitor of metalloproteinase 1
(TIMP 1), Cysteine-aspartic proteases 3 (Caspase 3), and tartrate-resistant acid phosphatase
(TRAP) positive osteoclast cells, osteoblast, and neutrophil counts were also determined.

Results and Discussion:
Alveolar bone loss was highest in P group, and differences among
P, Q75, and Q150 groups were significant. Both doses of quercetin decreased TRAP+ osteoclast
cells and increased osteoblast cells. Inflammation in P group was also higher than
those of C, Q75, and Q150 groups indicating anti-inflammatory effect of quercetin. iNOS,
MMP-8, and caspase-3 levels were highest, and TIMP-1 expression was lowest in P group;
differences were statistically significant.

Conclusion:
Within limits of this study, it can be suggested that quercetin administration
may reduce alveolar bone loss by increasing osteoblastic activity, decreasing osteoclastic
activity, apoptosis, and inflammation in an experimental model of periodontitis.
Molecular Modeling of Substances Isolated from the Essential Oil of the Species Drimys angustifolia and Drimys brasiliensis
Authors: Conceição Neuziane Dias , de Souza Lucilene Rocha , Ferreira Jaderson Vieira , de Fátima Brito Brito Maiara , Pinheiro Abraão Alves , da Silva Karina Rufino , Taft Carlton Anthony , de Paula da Silva Carlos Henrique Tomich , Fonseca Gomes Madson Ralide , da Silva Hage-Melim Lorane Izabel 
Published: January 2020

Objectives:
Carry out an in silico study of chemical substances isolated from
the species: Drimys angustifolia and Drimys brasiliensis.

Methods:
A theoretical study of global reactivity, QSAR descriptors, MEP construction
and molecular docking was performed to analyze the interaction of substances with acetylcholinesterase
of Drosophila melanogaster and the prediction of skin permeation and toxicological
properties of the substances.

Results:
Chemical reactivity and molecular stability investigation suggest that the substance
which presents stability values similar to the standard substance D-limonene, was
Terpinen-4-ol. The MEPs of the investigated substances were evenly distributed along the
hydrogens and oxygens. The molecular docking studies suggest interesting and promising
results for the substance Myristicin. Regarding skin permeability, the results suggests low
skin absorption for all substances. Regarding toxicological properties, bicyclogermacrene
indicated non-carcinogenic and mutagenic activity.

Conclusion:
Our results suggest that the substance, bicyclogermacrene, is a potential candidate
for usage as a repellent.