bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of Vangl2 Attenuates the Inflammation Promoted by Wnt5a via MAPK and NF-κB Pathway in Chondrocytes.
Authors: Zhang Ke , Li Zhuoying , Lu Yunyang , Xiang Linyi , Sun Jiadong , Zhang Hong 
Published: December 2020

Abstract
Background: The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro, and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes.Methods: Chondrocytes were treated with IL-1β (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. Results: IL-1β induced the production of Vangl2, Wnt5a and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13 and IL-6 at both gene and protein levels, and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes.Conclusions: For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix, and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.
Cannabinoids Modulate Food Preference and Consumption in Drosophila Melanogaster
Authors: He Jianzheng , Tan Alice , Ng Si , Yu Fengwei 
Published: December 2020

Abstract
Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of their sensory functions. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.
ApoE4-carrying Human Astrocytes Oversupply Cholesterol into Neurons and Promote Aβ Generation
Authors: Lee Se-In , Jeong Woojin , Cho Sukhee , Lee Hyein , Jang Yonghee , Lin Yuan-Ta , Tsai Li-Huei , Seo Jinsoo 
Published: December 2020

Abstract
Background: The onset of Alzheimer’s disease (AD) typically occurs later in life. Recent genetic analysis of patients and unaffected individuals revealed multiple genetic variants associated with late-onset AD. One of the strongest genetic risk factors for AD is 𝜀4 allele of APOE encoding apolipoprotein (ApoE), which is predominantly expressed in astrocytes. The role and mechanism of ApoE in initiating AD-associated pathologies, including amyloid-β (Aβ) accumulation and neurodegeneration in neurons, remains to be elucidated.Methods: Human induced pluripotent stem cells (hiPSCs) from healthy individuals and isogenic cells in which the ApoE 𝜀3 allele was replaced with an 𝜀4 allele were selected to generate human neurons and astrocytes. To investigate the effect of astrocytic ApoE4 on neuronal Aβ production, iPSC-derived neurons carrying the ApoE 𝜀3 allele were cultured in conditioned media from healthy iPSC-derived astrocytes (ApoE3/E4 heterozygote) for five weeks. Then, the media were replaced with either ApoE3 or ApoE4 astrocyte conditioned media (ACM), cultured for four days, and neuronal amyloid precursor protein (APP) expression and Aβ production were measured. To determine potential mechanisms for upregulation of APP in neurons by ApoE4 ACM, changes in plasma membrane lipid rafts were investigated by staining for cholera toxin B. Methyl-b-cyclodextrin (MβCD) was applied to deplete cholesterol in ApoE4 ACM.Results: Secretory factors in conditioned media from hiPSC-derived astrocytes carrying APOE4 significantly increased the levels of APP and Aβ secretion in hiPSC-derived neurons. Increasing cholesterol levels in culture media mimicked the effects of ApoE4 ACM by inducing the formation of lipid rafts that potentially provide a physical platform for APP localization on the membrane. We further found that reducing cholesterol levels in ApoE4 ACM with MβCD abolished its effects on neuronal lipid raft expansion and Aβ generation.Conclusions: Our study suggests that ApoE4 astrocytes contribute to amyloidosis by the expansion of lipid rafts and facilitate neuronal Ab production through oversupply of cholesterol.
Dramatic Response to Pembrolizumab with Chemotherapy Followed by Salvage Surgery in a Lung Cancer Patient
Authors: Saito Shunichi , Toyokawa Gouji , Momosaki Seiya , Kozuma Yuka , Shoji Fumihiro , Yamazaki Koji , Takeo Sadanori 
Published: December 2020

Abstract
Background: Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non-small-cell lung carcinoma and are under investigation as an induction therapy. But the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resected non-small-cell lung carcinoma still remains unclear. Case presentation: We herein report a case of stage IIIB non-small-cell lung carcinoma who underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab-paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in less than one percent of the total tumorous lesion suggesting near pathological complete response. Conclusions: This case suggests that this regimen might be a good option as induction therapy for non-small-cell lung carcinoma.
Social Capital and Chemsex Initiation in Young Gay, Bisexual, and Other Men Who Have Sex With Men: the Pink Carpet Y Cohort Study
Authors: Tan Rayner Kay Jin , O'Hara Caitlin Alsandria , Koh Wee Ling , Le Daniel , Tan Avin , Tyler Adrian , Tan Calvin , Kwok Chronos , Banerjee Sumita , Wong Mee Lian 
Published: December 2020

Abstract
Background: Young gay, bisexual, and other men who have sex with men (YMSM) are especially vulnerable to the risks associated with sexualized substance use, or ‘chemsex’. Engaging in chemsex established as a major risk factor for Human Immunodeficiency Virus (HIV) acquisition, and is thus a public health issue of increasing urgency. This paper attempts to explore the association between measures of social capital and patterns of sexualized substance use among a sample of YMSM in Singapore.Methods: Results of this study were derived from baseline data of the Pink Carpet Y Cohort Study in Singapore, comprising a sample of 570 HIV-negative YMSM aged 18 to 25 years old. Latent class analysis was employed to identify classes with similar patterns of sexualized substance use, and multinomial logistic regression was employed to examine associations between class membership and measures of social capital. Logistic regression was employed to examine associations between measures of social capital and past sexualized substance use.Results: Latent class analysis revealed three classes of YMSM based on their histories of sexualized substance use, which we labelled as ‘substance-naïve’, ‘substance-novice’, and ‘chemsex’. Participants with a later age of sexual debut were increasingly less likely to be in the substance novice and chemsex classes, compared to the substance-naïve class; they were also less likely to report sexualized alcohol, poppers and methamphetamine use. Connectedness to the lesbian, gay, bisexual and transgender (LGBT) community was negatively associated with sexualized methamphetamine use, while outness to family was positively associated with sexualized methamphetamine and erectile dysfunction drug use.Conclusions: Varying measures of social capital such as an earlier age of exposure to sexual networks or family-related stress may predispose YMSM to greater opportunities for sexualized substance use, while on the other hand, community connectedness may be protective. Future interventions should target YMSM who become sexually active at an earlier age to reduce the risks associated with sexualized substance use.
Association of Genetic Variants in TPMT, ITPA,&nbsp;NUDT15&nbsp;With&nbsp;Azathioprine-Induced Myelosuppression in Southwest China Patients With Autoimmune Hepatitis
Authors: Miao Qiang , Yan Lin , Zhou Yanhong , Li Yi , Zou Yuangao , Wang Lanlan , Bai Yangjuan , Zhang Junlong 
Published: December 2020

Abstract
Aims: To investigate the influence of TPMT*3C, ITPA, NUDT15, and 6-thioguanine nucleotides (6-TGN) on AZA-induced myelosuppression in Southwest China AIH patients. Methods: A total of 113 Chinese AIH patients with AZA maintenance treatment were evaluated. Collect the relevant clinical data of patients from the hospital information system. TPMT*3C(rs1142345), ITPA(rs1127354) and NUDT15(rs116855232) genotyping was detected by TaqMan double fluorescent probe. The concentration of 6-TGN was determined using UPLC-MS/MS method. Results: 40 (35.4%) patients had different degrees of myelosuppression. The NUDT15 variant was associated with leukopenia (P=8.26X10-7; OR=7.5; 95% CI, 3.08–18.3) and neutropenia (P=3.54X10-6; OR=8.05; 95% CI, 2.96–21.9). However, no significant association was observed for TPMT*3C and ITPA variants (P>0.05). There was no significant difference of 6-TGN concentration between patients with or without myelosuppression (P= 0.556), and no association was found in patients with TPMT*3C, ITPA, NUDT15 variants alleles (P>0.05). However, we found that the body mass index may affect the corrected 6-TGN level (P=0.026). Conclusion: Our study once again confirmed that NUDT15 variants are a potential independent risk predictor for AZA-induced leukopenia and neutropenia. Also, we found that the detection of 6-TGN concentration in red blood cells does not reflect AZA treatment's efficacy and toxicity. New biomarkers for AZA therapeutic drug monitoring need further research to explore.
Theory of the sp - d Coupling of Transition Metal Impurities with Free Carriers in ZnO
Authors: Ciechan Anna , Bogusławski Piotr 
Published: December 2020

Abstract
The s, p-d exchange coupling between the spins of band carriers and of transition metal (TM) dopants ranging from Ti to Cu in ZnO is studied within the density functional theory. The +U corrections are included to reproduce the experimental ZnO band gap and the dopant levels. The p- d coupling reveals unexpectedly complex features. In particular, (i) the p-d coupling constants N0β vary about 10 times when going from V to Cu, (ii) not only the value but also the sign of N0β depends on the charge state of the dopant, (iii) the p-d coupling with the heavy holes and the light holes is not the same; in the case of Fe, Co and Ni, N0βs for the two subbands can differ twice, and for Cu the opposite sign of the coupling is found for light and heavy holes. The main features of the p-d coupling are determined by the p-d hybridization between the d(TM) and p(O) orbitals. In contrast, the s-d coupling constant N0α is almost the same for all TM ions, and does not depend on the charge state of the dopant. The TM-induced spin polarization of the p(O) orbitals contributes to the s-d coupling, enhancing N0α.
Microfluidic Overhauser DNP Chip for Signal-enhanced Compact NMR
Authors: Kiss Sebastian , MacKinnon Neil , Korvink Jan 
Published: December 2020

Abstract
Nuclear magnetic resonance at low field strength is an insensitive spectroscopic technique, precluding portable applications with small sample volumes, such as needed for biomarker detection in body fluids. Here we report a compact double resonant chip stack system that implements in situ dynamic nuclear polarisation of a 130 nL sample volume, achieving a signal enhancement of 54 w.r.t. the thermal equilibrium level at a microwave power level of 0.5W. This work overcomes instrumental barriers to the use of NMR detection for point-of-care applications.
Enhanced Lung Inflammatory Response in Whole-body Compared to Nose-only Cigarette Smoke-exposed Mice
Authors: Serré Jef , Tanjeko Ajime Tom , Mathyssen Carolien , Vanherwegen An-Sofie , Heigl Tobias , Janssen Rob , Verbeken Eric , Maes Karen , Vanaudenaerde Bart , Janssens Wim , Gayan-Ramirez Ghislaine 
Published: December 2020

Abstract
Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization, uptake of gases through the skin or uptake of tar particles stuck on the skin via grooming. Methods: In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung remodeling and inflammation. Data was analyzed with a one-way ANOVA with Bonferroni post-hoc test or Kruskal-Wallis with Dunn’s test for multiple comparison depending on respectively parametric or non-parametric datasets.Results: Both CS exposure systems induced a similar degree of lung function impairment and morphological alterations. Interestingly, an enhanced lymphoid presence in the bronchoalveolar lavage and lymph nodes with a higher mRNA expression of interleukin 6 and keratinocyte chemoattractant in the lungs were found with the whole-body system. Conclusion: Our data indicate that the inflammatory outcomes are more severe in the whole-body CS exposure compared to the nose-only system, but lung remodeling and lung function impairment are similarly affected. These observations can assist researchers to make an appropriate choice between the two CS exposure systems in designing their future studies in early drug interventions.
Association Between Different Lipid Ratios and Diabetes in Chinese Adults With H-type Hypertension
Authors: tao yu , Yu Yu , Bao Huihui , Cheng Xiaoshu 
Published: December 2020

Abstract
Background: Previous studies have shown that lipid ratios [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C), atherogenic index of plasma (AIP, lg [triglyceride (TG)/HDL-C]), low-density lipoprotein cholesterol (LDL-C)/HDLC, non-HDL-C/HDL-C] were associated with the risk of diabetes in non-hypertension population. However, the relationship between different lipid ratios and diabetes is unclear in the H-type hypertension population. The purpose of this study is to investigate the relationship between lipid ratios and diabetes in Chinese adults with H- type hypertension.Methods: The current study included 13,581 H-type hypertension participants from the China hypertension registry study. Logistic regression analysis and smooth curve fitting were used to assess the association between different lipid ratios and diabetes.Results: Prevalence of diabetes was 17.8%. All lipid ratios (TC/HDL-C, AIP, LDL-C/HDL-C, and non-HDL-C/HDL-C) were positively and independently associated with diabetes. In the fully adjusted model, AIP manifested the largest ORs of diabetes (OR:2.84, 95%CI:2.37-3.41). However, the fully adjusted ORs (95%CI) of TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C ratio was only 1.34 (1.27, 1.43), 1.40 (1.29, 1.51), 1.42 (1.35, 1.50), respectively. Comparing the area under receiver-operating characteristic curve (AUC), we found that AIP had the stronger ability to identify diabetes.Conclusions: all lipid ratios (TC/HDL-C, AIP, LDL-C/HDL-C, and non-HDL-C/HDL-C) were independently and positively correlated with the risk of diabetes in the Chinese population with H-type hypertension. Compared with other lipid ratios (TC/HDL-C, LDL-C/HDL-C, and non-HDL-C/HDL-C), AIP was superior in discriminating diabetes.
Food Aversion During Pregnancy and Its Association With Nutritional Status of Pregnant Women in Boricha Woreda, Sidama Zone, Southern Ethiopia, 2019. A Community Based Mixed Crossectional Study Design
Authors: Yalew Abel , T/Silasie Wondwosen , Anato Anchamo , Fikrie Anteneh 
Published: December 2020

Abstract
Background: Despite high prevalence, food aversions are closely linked to the dietary intake of pregnant women. Thus, understanding this behavior is important in addressing the issue of maternal nutrition. Therefore, the aim of this study is to provide information on the prevalence and associated factors of food aversion and its relationship with the nutritional status of pregnant women in Boricha Woreda, Sidama Zone, Southern Ethiopia, 2019.Methods: A community based mixed cross sectional study was conducted among 505 randomly selected pregnant mothers at Boricha Woreda, Southern Ethiopia from June 1-20, 2019. Pre-tested and structured face-to-face interview questionnaire and focus group discussion guide were used to collect quantitative and qualitative data respectively. The quantitative data were cleaned, coded and entered into Epi Info version 7.1.4.0 and then exported to SPSS IBM version 20 for further analysis. The qualitative data were analyzed manually using a content analysis.The bi-variable and multivariable logistic regression was used to identify the possible factors of food aversion. Pearson’s Chi-square test was used to assess the relationship between food aversion and nutritional status of pregnant women. AOR with the respective 95% CIs was used to declare statistical significance.Results: Nearly, seven-in-ten (69.2%) of the pregnant women were averted of at least one food. Cereal (45.9%) and enset (44.2%) were averted by majority of the participants. The mean (±SD) MUAC measurement was 22.7 (±2.4) cm. For age group 19 – 23 [AOR= 2.36, 95%CI (1.32 – 4.21)] and 24 – 28 of years [AOR= 2.84, 95% CI (1.61 – 5.01)], nausea [AOR= 1.70, 95%CI (1.10 – 2.65)] and having additional meal [AOR= 1.70, 95% CI (1.06 – 2.73)] were significantly associated with food aversion. Maternal nutritional status and food aversion was statistically significant (p-value=0.008).Conclusion: High prevalence of food aversions (69.2%) and under nutrition (34.6%) among pregnant women is found. Therefore, the Woreda Health Office needs to intensify the integration of maternal nutrition into ANC services and training of health providers as well as critical appraisal of health extension workers should also be considered.
Barriers to accessing maternal and newborn care: a qualitative study in district Thatta, Pakistan
Authors: Asim Muhammad , Saleem Sarah , Ahmad Zarak Hussain , Naeem Imran , Abrejo Farina , Fatmi Zafar , Siddiqi Sameen 
Published: December 2020

Abstract
Background: Accessibility and utilization of health care play a significant role in preventing complications during pregnancy, labor, and the early postnatal period. However, multiple barriers can prevent women from accessing pregnancy and neonatal care. The aim of this study was to explore the multifaceted barriers that inhibit women to seek maternal and newborn health care in Thatta, Sindh, Pakistan.Methods: This study employed an interpretive research design using purposive sampling approach. Pre-tested semi-structured interview guides were used for data collection. The data were collected through eight focus group discussions with men and women, and six in-depth interviews with lady health workers and analyzed through thematic analysis. Findings: The study identified individual, socio-cultural, and structural level barriers that inhibit women from seeking maternal and newborn care. Individual barriers included: mistrust towards public health facilities, and inadequate symptom recognition. The two identified socio-cultural barriers were: aversion to biomedical interventions, and gendered imbalances in decision making. The structural barriers included: prohibitively expensive transportation services, and ineffective referral systems. Conclusion and Suggestions: Increasing the coverage of healthcare service without addressing the multifaceted barriers that influence service utilization will not reduce the burden of maternal and neonatal mortality. As this study reveals, care seeking is influenced by a diverse array of barriers that are individual, sociocultural, and structural in nature. A combination of capacity development, health awareness, and structural interventions can address many if not all of these barriers.