bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Among Inflammation, Overweight Status, and Cognitive Impairment in a Community-Based Population of Chinese Adults
Authors: Wang Jing , Wang Anxin , Zhao Xingquan 
Published: December 2020

Purpose: To determine the association between overweight and high-sensitivity C-reactive protein (hs-CRP) with the odds of cognitive impairment as well as its subtypes based on the Asymptomatic Polyvascular Abnormalities Community (APAC) study in China.Materials and methods: We conducted a cross-sectional analysis of the follow-up data of 2012 from the APAC study. The Chinese version of the MMSE was used as a cognitive screener, and an MMSE score &lt;24 is generally accepted as indicating cognitive impairment. Multivariable logistic regression was used to estimate the interactions of hs-CRP levels with body mass index (BMI) on the effects of cognitive impairment and its subtypes.Results: Three thousand eight hundred seventy-five participants aged 40–90 years (median age 51.64 y) were enrolled in this study, and 1,788 (46.1%) were overweight. Before and after adjusting for confounders, such as age, sex, BMI, education, current smoking, drinking, physical activity, hypertension, hyperlipidemia, diabetes, and hs-CRP, elevated hs-CRP levels were associated with cognitive impairment in normal-weight participants (crude OR: 2.08, 95%CI: 1.28–3.37, p = 0.003; adjusted OR: 2.06, 95%CI: 1.03–4.10, p = 0.04), but not in overweight participants. There was no statistically significant evidence for the interaction between hs-CRP and BMI on any cognitive sub-item.Conclusion: Elevated hs-CRP levels increase the odds of cognitive impairment in normal-weight participants, but not in overweight participants.
Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion
Authors: Wang Rong-hui , Dai Xue-jing , Wu Hong , Wang Meng-die , Deng Ran , Wang Yan , Bu Yan-hong , Sun Ming-hui , Zhang Heng 
Published: December 2020

The activated Gα protein subunit (Gαs) and the inhibitory Gα protein subunit (Gαi) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Gαi/Gαs can couple with sphingosine-1-phosphate receptors (S1PRs) and have a critical role in rheumatoid arthritis (RA). Through binding to S1PRs, sphingosine-1-phosphate (S1P) leads to activation of the pro-inflammatory signaling in rheumatoid arthritis synovial fibroblasts (RASFs). Geniposide (GE) can alleviate RASFs dysfunctions to against RA. However, its underlying mechanism of action in RA has not been elucidated so far. This study aimed to investigate whether GE could regulate the biological functions of MH7A cells by inhibiting S1PR1/3 coupling Gαi/Gαs conversion. We use RASFs cell line, namely MH7A cells, which were obtained from the patient with RA and considered to be the main effector cells in RA. The cells were stimulated with S1P (5 μmol/L) and then were treated with or without different inhibitors: Gαi inhibitor pertussis toxin (0.1 μg/mL), S1PR1/3 inhibitor VPC 23019 (5 μmol/L), Gαs activator cholera toxin (1 μg/mL) and GE (25, 50, and 100 μmol/L) for 24 h. The results showed that GE may inhibit the abnormal proliferation, migration and invasion by inhibiting the S1P-S1PR1/3 signaling pathway and activating Gαs or inhibiting Gαi protein in MH7A cells. Additionally, GE could inhibit the release of inflammatory factors and suppress the expression of cAMP, which is the key factor of the conversion of Gαi and Gαs. GE could also restore the dynamic balance of Gαi and Gαs by suppressing S1PR1/3 and inhibiting Gαi/Gαs conversion, in a manner, we demonstrated that GE inhibited the activation of Gα downstream ERK protein as well. Taken together, our results indicated that down-regulation of S1PR1/3-Gαi/Gαs conversion may play a critical role in the effects of GE on RA and GE could be an effective therapeutic agent for RA.
Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Approach
Authors: Liu Shuaibing , Wang Ziteng , Tian Xin , Cai Weimin 
Published: December 2020

Vicagrel, a novel acetate derivative of clopidogrel, exhibits a favorable safety profile and excellent antiplatelet activity. Studies aim at identifying genetic and non-genetic factors affecting vicagrel metabolic enzymes Cytochrome P450 2C19 (CYP2C19), Carboxylesterase (CES) 1 and 2 (CES1 and CES2), which may potentially lead to altered pharmacokinetics and pharmacodynamics, are warranted. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating vicagrel and its metabolites was constructed, verified and validated in our study, which could simultaneously characterize its sequential two step metabolism and clinical response. Simulations were then performed to evaluate the effects of CYP2C19, CES1 and CES2 genetic polymorphisms as well as inhibitors of these enzymes on vicagrel pharmacokinetics and antiplatelet effects. Results suggested vicagrel was less influenced by CYP2C19 metabolic phenotypes and CES1 428 G &gt; A variation, in comparison to clopidogrel. No pharmacokinetic difference in the active metabolite was also noted for volunteers carrying different CES2 genotypes. Omeprazole, a CYP2C19 inhibitor, and simvastatin, a CES1 and CES2 inhibitor, showed weak impact on the pharmacokinetics and pharmacodynamics of vicagrel. This is the first study proposing a dynamic PBPK/PD model of vicagrel able to capture its pharmacokinetic and pharmacodynamic profiles simultaneously. Simulations indicated that genetic polymorphisms and drug-drug interactions showed no clinical relevance for vicagrel, suggesting its potential advantages over clopidogrel for treatment of cardiovascular diseases. Our model can be utilized to support further clinical trial design aiming at exploring the effects of genetic polymorphisms and drug-drug interactions on PK and PD of this novel antiplatelet agent.
Barriers and Opportunities for Implementation of Outcome-Based Spread Payments for High-Cost, One-Shot Curative Therapies
Authors: Michelsen Sissel , Nachi Salma , Van Dyck Walter , Simoens Steven , Huys Isabelle 
Published: December 2020

Background: The challenging market access of high-cost one-time curative therapies has inspired the development of alternative reimbursement structures, such as outcome-based spread payments, to mitigate their unaffordability and answer remaining uncertainties. This study aimed to provide a broad overview of barriers and possible opportunities for the practical implementation of outcome-based spread payments for the reimbursement of one-shot therapies in European healthcare systems.Methods: A systematic literature review was performed investigating published literature and publicly available documents to identify barriers and implementation opportunities for both spreading payments and for implementing outcome-based agreements. Data was analyzed via qualitative content analysis by extracting data with a reporting template.Results: A total of 1,503 publications were screened and 174 were included. Main identified barriers for the implementation of spread payments are reaching an agreement on financial terms while considering 12-months budget cycles and the possible violation of corresponding international accounting rules. Furthermore, outcome correction of payments is currently hindered by the need for additional data collection, the lack of clear governance structures and the resulting administrative burden and cost. The use of spread payments adjusted by population- or individual-level data collected within automated registries and overseen by a governance committee and external advisory board may alleviate several barriers and may support the reimbursement of highly innovative therapies.Conclusion: High-cost advanced therapy medicinal products pose a substantial affordability challenge on healthcare systems worldwide. Outcome-based spread payments may mitigate the initial budget impact and alleviate existing uncertainties; however, their effective implementation still faces several barriers and will be facilitated by realizing the required organizational changes.
Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways
Authors: Huang Wen-wen , Hong Bi-hong , Bai Kai-kai , Tan Ran , Yang Ting , Sun Ji-peng , Yi Rui-zao , Wu Hao 
Published: December 2020

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms wherebycis-palmitoleic acid (cPOA) andtrans-palmitoleic acid (tPOA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects ofcPOA andtPOA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administeredcPOA ortPOA once daily for 4 weeks.tPOA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely,cPOA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed thatcPOA ameliorated hepatic steatosis more effectively thantPOA.tPOA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereascPOA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest thatcPOA andtPOA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore,tPOA, but notcPOA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dosetPOA andcPOA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1.tPOA andcPOA prevent hypercholesterolemia via distinct mechanisms.
Exercise Training and Neurodegeneration in Mitochondrial Disorders: Insights From the Harlequin Mouse
Authors: Fernández-de la Torre Miguel , Fiuza-Luces Carmen , Valenzuela Pedro L. , Laine-Menéndez Sara , Arenas Joaquín , Martín Miguel A. , Turnbull Doug M. , Lucia Alejandro , Morán María 
Published: December 2020

AimCerebellar neurodegeneration is a main phenotypic manifestation of mitochondrial disorders caused by apoptosis-inducing factor (AIF) deficiency. We assessed the effects of an exercise training intervention at the cerebellum and brain level in a mouse model (Harlequin, Hq) of AIF deficiency.MethodsMale wild-type (WT) and Hq mice were assigned to an exercise (Ex) or control (sedentary [Sed]) group (n = 10–12/group). The intervention (aerobic and resistance exercises) was initiated upon the first symptoms of ataxia in Hq mice (∼3 months on average) and lasted 8 weeks. Histological and biochemical analyses of the cerebellum were performed at the end of the training program to assess indicators of mitochondrial deficiency, neuronal death, oxidative stress and neuroinflammation. In brain homogenates analysis of enzyme activities and levels of the oxidative phosphorylation system, oxidative stress and neuroinflammation were performed.ResultsThe mean age of the mice at the end of the intervention period did not differ between groups: 5.2 ± 0.2 (WT-Sed), 5.2 ± 0.1 (WT-Ex), 5.3 ± 0.1 (Hq-Sed), and 5.3 ± 0.1 months (Hq-Ex) (p = 0.489). A significant group effect was found for most variables indicating cerebellar dysfunction in Hq mice compared with WT mice irrespective of training status. However, exercise intervention did not counteract the negative effects of the disease at the cerebellum level (i.e., no differences for Hq-Ex vs. Hq-Sed). On the contrary, in brain, the activity of complex V was higher in both Hq mice groups in comparison with WT animals (p &lt; 0.001), and post hoc analysis also revealed differences between sedentary and trained Hq mice.ConclusionA combined training program initiated when neurological symptoms and neuron death are already apparent is unlikely to promote neuroprotection in the cerebellum of Hq model of mitochondrial disorders, but it induces higher complex V activity in the brain.
Metabolic Engineering Strategies of Industrial Hemp (Cannabis sativa L.): A Brief Review of the Advances and Challenges
Authors: Deguchi Michihito , Kane Shriya , Potlakayala Shobha , George Hannah , Proano Renata , Sheri Vijay , Curtis Wayne R. , Rudrabhatla Sairam 
Published: December 2020

Industrial hemp (Cannabis sativa L.) is a diploid (2n = 20), dioecious plant that is grown for fiber, seed, and oil. Recently, there has been a renewed interest in this crop because of its panoply of cannabinoids, terpenes, and other phenolic compounds. Specifically, hemp contains terpenophenolic compounds such as cannabidiol (CBD) and cannabigerol (CBG), which act on cannabinoid receptors and positively regulate various human metabolic, immunological, and physiological functions. CBD and CBG have an effect on the cytokine metabolism, which has led to the examination of cannabinoids on the treatment of viral diseases, including COVID-19. Based on genomic, transcriptomic, and metabolomic studies, several synthetic pathways of hemp secondary metabolite production have been elucidated. Nevertheless, there are few reports on hemp metabolic engineering despite obvious impact on scientific and industrial sectors.In this article, recent status and current perspectives on hemp metabolic engineering are reviewed. Three distinct approaches to expedite phytochemical yield are discussed. Special emphasis has been placed on transgenic and transient gene delivery systems, which are critical for successful metabolic engineering of hemp. The advent of new tools in synthetic biology, particularly the CRISPR/Cas systems, enables environment-friendly metabolic engineering to increase the production of desirable hemp phytochemicals while eliminating the psychoactive compounds, such as tetrahydrocannabinol (THC).
Leader Humility and Knowledge Sharing Intention: A Serial Mediation Model
Authors: Nguyen Diep T. N. , Teo Stephen T. T. , Halvorsen Beni , Staples Warren 
Published: December 2020

PurposeThis paper examines the influence of leader humility on knowledge sharing intention. Drawing on social exchange theory (SET), we test the direct and indirect mechanisms to explain the influence leader humility has on knowledge sharing intention.Design/Methodology/ApproachA two-wave, time-lagged field study was conducted. We surveyed 252 professional employees from Australia.FindingsResults show a significant direct, positive association between leader humility and knowledge sharing intention. While leader humility had a direct, positive association with affective trust in supervisor and work engagement, it did not directly impact on organizational citizenship behaviors directed toward the individual (OCB-I). There were three SET-related, serial mediators in the relationship between leader humility and knowledge sharing intention. These were affective trust, work engagement, and OCB-I.Research Limitations/ImplicationsFuture studies should collect multi-source data such as peers’ or supervisors’ ratings of the focal respondents’ work engagement, OCB-I, and knowledge sharing behaviors to augment single-source data. Future studies could adopt an affect theory of social exchange to further explore the relationships tested in this study.Originality/ValueThis study contributes to the affect SET and knowledge management literature on how leadership behaviors impact the intention to share knowledge. Our study highlights the preference of the willingness to share knowledge with their co-workers is mediated by affective trust in their immediate supervisors, work engagement, and OCB-I that are equally important as treating their subordinates with humility.
Outcomes of Visual Self-Expression in Virtual Reality on Psychosocial Well-Being With the Inclusion of a Fragrance Stimulus: A Pilot Mixed-Methods Study
Authors: Kaimal Girija , Carroll-Haskins Katrina , Ramakrishnan Arun , Magsamen Susan , Arslanbek Asli , Herres Joanna 
Published: December 2020

AimsIn this pilot mixed-methods study, we examined the participants experiences of engaging in virtual drawing tasks and the impact of an olfactory stimulus (calming fragrance blend) on outcomes of affect, stress, self-efficacy, anxiety, creative agency, and well-being (satisfaction with life).MethodsThis study used a parallel mixed-methods, simple block randomization design. The study participants included 24 healthy adults aged 18 to 54 years, including 18 women and six men. The participants completed two 1-h immersive virtual art making sessions and were randomly assigned to receive either a fragrance or a non-fragrance condition for the first session. Quantitative (standardized self-report measures) and qualitative (open-ended survey responses and virtual artwork) datasets were collected concurrently and integrated during data analysis.ResultsThe quantitative results indicated that the fragrance condition demonstrated a significant reduction in negative affect (e.g., feeling hostile, jittery, upset, distressed, etc.), namely, reduced feelings of negativity when compared to the non-fragrance condition. A trend toward improvement in self-efficacy was also seen in the fragrance condition. No significant changes were found for fragrance or non-fragrance conditions for positive affect, anxiety, and creative agency. The qualitative findings included five themes related to art making experiences in virtual reality in both conditions: fun and joy; novelty of virtual media, experimentation, and play; relaxation and calm; learning curve; and physical discomfort and disorientation. Four themes were identified for virtual art content and visual qualities: nature imagery, references to memories and personal symbols, fantasy and play within imagery, and depiction of everyday objects.ConclusionsOverall, the participants reported positive responses to the novel virtual art making experiences which were further heightened by the inclusion of the fragrance stimulus for negative affect. These preliminary findings need to be replicated with larger sample sizes to confirm the outcomes and the trends that were seen in this pilot study. Further research is recommended to examine the differences between experiences of virtual and traditional art media and to examine different olfactory stimuli promoting focus and concentration.
Personality Traits and Disorders in Adolescents at Clinical High Risk for Psychosis: Toward a Clinically Meaningful Diagnosis
Authors: Boldrini Tommaso , Tanzilli Annalisa , Di Cicilia Giuseppe , Gualco Ivan , Lingiardi Vittorio , Salcuni Silvia , Tata Maria Cristina , Vicari Stefano , Pontillo Maria 
Published: December 2020

Aims:Recent meta-analytic data show that approximately 40% of individuals at clinical high risk for psychosis (CHR) receive at least one personality disorder (PD) diagnosis. Personality pathology could significantly influence CHR patients' prognosis and response to treatment. We aimed at exploring the PD traits of CHR adolescents, in order to outline a prototypic description of their most frequently observed personality characteristics.Methods:One hundred and twenty-three psychiatrists and psychologists used a Q-sort procedure [i.e., the Shedler–Westen Assessment Procedure-200 for Adolescents (SWAP-200-A)] to assess personality traits and disorders in 58 (30 male; mean age = 16 years, range = 13–19 years) CHR adolescents and two gender- and age-matched samples, respectively, with (n= 60) and without PDs (n= 59).Results:Differences between the CHR, PD, and clinical groups showed that CHR adolescents had pervasive and more clinically relevant schizoid, schizotypal, borderline, and avoidant traits, as well as poorer adaptive functioning. Moreover, by collecting the highest mean SWAP-200-A items, we empirically outlined a prototypic description of CHR youths, comprised of avoidance of social relationships; suspiciousness; obsessional thoughts; lack of psychological insight; dysphoric and overwhelming feelings of anxiety and depression; odd and anomalous reasoning processes or perceptual experiences; symptoms of depersonalization and derealization; and negative symptoms of avolition, abulia, blunted affects, and impaired role functioning.Conclusions:The results suggest that avoidant interpersonal strategies, impaired mentalization, and difficulties in emotional regulation could become important targets for psychosocial interventions with CHR adolescent populations.
Addiction Recovery Among Opioid-Dependent Patients Treated With Injectable Subcutaneous Depot Buprenorphine: Study Protocol of a Non-randomized Prospective Observational Study (ARIDE)
Authors: Schulte Bernd , Lehmann Kirsten , Schmidt Christiane Sybille , Rühling Elke , Weber Bernd , Schäfer Ingo , Reimer Jens , Verthein Uwe 
Published: December 2020

Introduction: Once-weekly or once-monthly injectable depot buprenorphine is a new opioid substitution treatment (OST) medication that provides clinically relevant plasma concentrations without daily peaks. Together with a high tolerability and acceptance reported by patients, the prolonged release of injectable depot buprenorphine might have beneficial implications on the patients' quality of life and social participation. The primary objective of this prospective non-interventional observational study is to evaluate the effects of subcutaneous injectable depot buprenorphine on the quality of life of patients in routine OST care in Germany. Secondary outcomes like illicit substance use, psychological distress, social participation and activity are assessed to provide an overall evaluation toward addiction recovery.Methods and Analysis: The present study is a non-randomized prospective observational study with a control group (treatment-as-usual). To ensure comparability between both patient groups, suitable control patients (n = 213) from the same OST unit will be matched pairwise to each patient treated with injectable depot buprenorphine (n = 213). Matching variables are gender, duration of OST, take-home prescription and psychosocial functioning (according to the Global Assessment of Functioning scale). Primary study endpoint is the difference of change in quality of life, assessed with the recently developed Opioid Substitution Treatment Quality of Life scale (OSTQOL), within the depot buprenorphine group between baseline and month 12. The primary analysis will be carried out according to the intention-to-treat principle (ITT) by comparing OSTQOL mean scores using dependent t-tests. For secondary analyses, group comparisons will be done by mixed model approaches with baseline OSTQOL score and the (pairwise) cluster term as covariates.Discussion: The study combines clinical, routine OST care data with relevant patient reported outcome data. The pairwise matching allows conclusions on effects of different OST medications. The study findings will provide new insights in the addiction recovery processes of OST patients treated with depot buprenorphine.Ethics and Dissemination: The study protocol has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (Ärztekammer Hamburg) (reference number: PV7078). The study results will be disseminated through peer-reviewed publications and presentations on scientific conferences.Clinical Trial Registration: German Clinical Trials Register DRKS-ID: DRKS00020797