bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries
Authors: Li Jasmin Chendi , Velagic Anida , Qin Cheng Xue , Li Mandy , Leo Chen Huei , Kemp-Harper Barbara K. , Ritchie Rebecca H. , Woodman Owen L. 
Published: January 2021

Introduction:Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.
The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis In Vitro and Induces Vasodilatation Without Desensitisation In Vivo
Authors: Read Cai , Nyimanu Duuamene , Yang Peiran , Kuc Rhoda E. , Williams Thomas L. , Fitzpatrick Christopher M. , Foster Richard , Glen Robert C. , Maguire Janet J. , Davenport Anthony P. 
Published: January 2021

Signaling through the apelin receptor is beneficial for a number of diseases including pulmonary arterial hypertension. The endogenous small peptides, apelin and elabela/toddler, are downregulated in pulmonary arterial hypertension but are not suitable for exogenous administration owing to a lack of bioavailability, proteolytic instability and susceptibility to renal clearance. CMF-019, a small molecule apelin agonist that displays strong bias towards G protein signaling over β-arrestin (∼400 fold), may be more suitable. This study demonstrates that in addition to being a positive inotrope, CMF-019 caused dose-dependent vasodilatation in vivo (50 nmol 4.16 ± 1.18 mmHg, **p &lt; 0.01; 500 nmol 6.62 ± 1.85 mmHg, **p &lt; 0.01), without receptor desensitization. Furthermore, CMF-019 rescues human pulmonary artery endothelial cells from apoptosis induced by tumor necrosis factor α and cycloheximide (5.66 ± 0.97%, **p &lt; 0.01) by approximately 50% of that observable with rhVEGF (11.59 ± 1.85%, **p &lt; 0.01), suggesting it has disease-modifying potential in vitro. CMF-019 displays remarkable bias at the apelin receptor for a small molecule and importantly recapitulates all aspects of the cardiovascular responses to the endogenous ligand, [Pyr1]apelin-13, in vivo. Additionally, it is able to protect human pulmonary artery endothelial cells from apoptosis, suggesting that the beneficial effects observed with apelin agonists extend beyond hemodynamic alleviation and address disease etiology itself. These findings support CMF-019 as a G protein biased small molecule apelin agonist in vitro and in vivo that could form the basis for the design of novel therapeutic agents in chronic diseases, such as, pulmonary arterial hypertension.
Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation
Authors: Blažević Tina , Reznicek Gottfried , Ding Limin , Yang Gangqiang , Haiss Patricia , Heiss Elke H. , Dirsch Verena M. , Liu Rongxia 
Published: January 2021

Rosmarinic acid is a natural phenolic acid and active compound found in many culinary plants, such as rosemary, mint, basil and perilla. Aiming to improve the pharmacokinetic profile of rosmarinic acid and its activity on vascular smooth muscle cell proliferation, we generated a series of rosmarinic acid esters with increasing alkyl chain length ranging from C1 to C12. UHPLC-MS/MS analysis of rat blood samples revealed the highest increase in bioavailability of rosmarinic acid, up to 10.52%, after oral administration of its butyl ester, compared to only 1.57% after rosmarinic acid had been administered in its original form. When added to vascular smooth muscle cells in vitro, all rosmarinic acid esters were taken up, remained esterified and inhibited vascular smooth muscle cell proliferation with IC50 values declining as the length of alkyl chains increased up to C4, with an IC50 of 2.84 µM for rosmarinic acid butyl ester, as evident in a resazurin assay. Vascular smooth muscle cells were arrested in the G0/G1 phase of the cell cycle and the retinoblastoma protein phosphorylation was blocked. Esterification with longer alkyl chains did not improve absorption and resulted in cytotoxicity in in vitro settings. In this study, we proved that esterification with proper length of alkyl chains (C1–C4) is a promising way to improve in vivo bioavailability of rosmarinic acid in rats and in vitro biological activity in rat vascular smooth muscle cells.
The Experimental TASK-1 Potassium Channel Inhibitor A293 Can Be Employed for Rhythm Control of Persistent Atrial Fibrillation in a Translational Large Animal Model
Authors: Wiedmann Felix , Beyersdorf Christoph , Zhou Xiao-Bo , Kraft Manuel , Foerster Kathrin I. , El-Battrawy Ibrahim , Lang Siegfried , Borggrefe Martin , Haefeli Walter E. , Frey Norbert , Schmidt Constanze 
Published: January 2021

BackgroundUpregulation of the two-pore-domain potassium channel TASK-1 (hK2P3.1) was recently described in patients suffering from atrial fibrillation (AF) and resulted in shortening of the atrial action potential. In the human heart, TASK-1 channels facilitate repolarization and are specifically expressed in the atria. In the present study, we tested the antiarrhythmic effects of the experimental ion channel inhibitor A293 that is highly affine for TASK-1 in a porcine large animal model of persistent AF.MethodsPersistent AF was induced in German landrace pigs by right atrial burst stimulation via implanted pacemakers using a biofeedback algorithm over 14 days. Electrophysiological and echocardiographic investigations were performed before and after the pharmacological treatment period. A293 was intravenously administered once per day. After a treatment period of 14 days, atrial cardiomyocytes were isolated for patch clamp measurements of currents and atrial action potentials. Hemodynamic consequences of TASK-1 inhibition were measured upon acute A293 treatment.ResultsIn animals with persistent AF, the A293 treatment significantly reduced the AF burden (6.5% vs. 95%; P &lt; 0.001). Intracardiac electrophysiological investigations showed that the atrial effective refractory period was prolonged in A293 treated study animals, whereas, the QRS width, QT interval, and ventricular effective refractory periods remained unchanged. A293 treatment reduced the upregulation of the TASK-1 current as well as the shortening of the action potential duration caused by AF. No central nervous side effects were observed. A mild but significant increase in pulmonary artery pressure was observed upon acute TASK-1 inhibition.ConclusionPharmacological inhibition of atrial TASK-1 currents exerts in vivo antiarrhythmic effects that can be employed for rhythm control in a porcine model of persistent AF. Care has to be taken as TASK-1 inhibition may increase pulmonary artery pressure levels.
Sports and Functional Training Improve a Subset of Obesity-Related Health Parameters in Adolescents: A Randomized Controlled Trial
Authors: Branco Braulio Henrique Magnani , Mariano Isabela Ramos , de Oliveira Leonardo Pestillo , Bertolini Sônia Maria Marques Gomes , de Oliveira Fabiano Mendes , Araújo Cynthia Gobbi Alves , Adamo Kristi 
Published: January 2021

To investigate the effects of two different modes of physical activity on body composition, physical fitness, cardiometabolic risk, and psychological responses in female adolescents participating in a multi-disciplinary program. The 12-week randomized intervention included 25-adolescents with overweight divided into two groups: sports practice-SPG and functional training-FTG. The SPG intervention was divided into three sports: basketball, handball, and futsal. SPG participants performed one sport 3-times/week, over the course of 1 month. The FTG performed concurrent exercises 3-times/week. This study was registered in Clinical Trials Registry Platform under number: RBR-45ywtg and registered in Local Ethics Committee number: 2,505.200/2018. The intensity of physical exercises-PE was matched between groups by the rating of perceived exertion. The primary outcome was body composition, and secondary outcomes were physical fitness, cardiometabolic risk, and psychological responses. There was a significant time-effect for body mass, body mass index, and low-density lipoprotein (LDL-c), all being reduced. There were increases over time for musculoskeletal mass, aerobic fitness, and high-density lipoprotein (HDL-c) (p &lt; 0.05). There was a group time interaction with body fat percentage being lower post-intervention in the SPG (p &lt; 0.05). No significant differences were observed for the other variables. Both physical activity models were effective in improving a subset of obesity-related health parameters. The findings should be extended by further investigation using more sophisticated measures of energy expenditure.Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-45ywtg.
Feasibility and Effectiveness of a New Short-Term Psychotherapy Concept for Adolescents With Emotional Dysregulation
Authors: Dixius Andrea , Möhler Eva 
Published: January 2021

Background:The ‘Stress-Trauma-Symptoms-Regulation-Treatment’ (START) is an innovative manualized short-term treatment program for stabilization and stress resilience in emotionally dysregulated adolescents, based on an approach of stress and management and emotional regulation. The current pilot trial aims to assess the feasibility and effectiveness of the START intervention program for improvement of emotion regulation.Methods:Sixty-six adolescents between the age of 13–18 years admitted to a psychiatric unit for acute emotional or behavioral dysregulation took part in the START program for 5 weeks in an open group setting with two sessions per week (70 min/session). Before treatment, we assessed a history of adverse experience with the Child and Adolescent Trauma Screen (CATS) and the Child Posttraumatic Cognitions Inventory (CPTCI). Before and after treatment, the participants completed the FEEL-KJ, a self-report screening instrument of emotional regulation and coping strategies.Results:A large proportion of this sample had experienced traumatic events based on the CATS (75%) and the CPTCI (82%). The mean FEEL-KJ score significantly decreased after the intervention (d= −0.248,p= 0.037), while no difference was observed with regard to mean level of adaptive emotion regulation strategies (d= 0.202,p= 0.207). A positive effect of the intervention was observed on three components of the adaptive FEEL-KJ scale: accepting(d= 0.289,p= 0.08), forgetting (d= 0.271,p= 0.049) and dealing with anger (d= 0.309,p= 0.034).Conclusion:START demonstrates preliminary evidence for improvement in emotional dysregulation after a 5-weeks course of treatment. Therefore, this short-term intervention can possibly be regarded as a tool to improve emotional stability in children with a high load of trauma-related psychopathology. The results are promising and warrant future studies, specifically randomized controlled trials on the effectiveness of START for strengthening resilience at-risk-populations.
Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia
Authors: Kumar Pooja , Kraal A. Zarina , Prawdzik Andreas M. , Ringold Allison E. , Ellingrod Vicki 
Published: January 2021

Introduction:Schizophrenia is a lifelong condition associated with several comorbid conditions such as physical illnesses like obesity, as well as co-occurring psychiatric symptoms such as depression. Research regarding susceptibility to some of these comorbidities has primary focused on genetic risks or neurotransmitters and very little work has been done to understand environmental factors such as diet. In particular, understanding the role of dietary glutamic acid consumption on co-morbidities in patients with schizophrenia is important, as evidence suggests that glutamic acid consumption may directly influence glutamatergic neurotransmission; a key neurotransmitter related to schizophrenia, its associated co-morbidities, and depression. Therefore, the aim of this study was to examine the potential relationship between dietary glutamic acid and depressive symptomatology in patients with schizophrenia, stratified by obesity status, due to its relationship with inflammation, antipsychotic use, and depressive symptoms.Methods:Subjects included in this analysis, were part of a parent cross-sectional study in which included three dietary recalls analyzed using protocols outlined as part of the National Health and Nutrition Examination Surveys (NHANES) standardized criteria. Additionally, body mass index (BMI), and Beck Depression Inventory were obtained at this visit. Subjects with a BMI ≥ 30 kg/m2were included in the obesity group, and the relationship between glutamic acid consumption and BDI scores was analyzed after controlling for age, race, sex, antidepressant and antipsychotic use, and animal and vegetable protein intake which provide natural forms of dietary glutamic acid.Results:A total of 168 participants were included in this study, of which 42.5% were female and 52.9% were White. The mean BMI for the group as a whole was 33.5 ± 8.7 (kg/m2) and the mean BDI was 14.5 ± 10.2 (range 2–50). No differences were found between obesity groups, other than a greater hyperlipidemia, hypertension, and lower waist to hip ratio. Overall, no relationship was found between dietary glutamic acid and BDI scores, However, for non-obese participants, diets higher levels of glutamic acid were associated with greater depression symptomatology (p= 0.021).Conclusion:These preliminary results indicate a possible correlation between dietary glutamic acid a depressive symptoms in non-obese patients with schizophrenia, although further research is needed to specifically examine this relationship.
Clustering and Healthcare Costs With Multiple Chronic Conditions in a US Study
Authors: Hajat Cother , Siegal Yakir , Adler-Waxman Amalia 
Published: January 2021

Objective: To investigate healthcare costs and contributors to costs for multiple chronic conditions (MCCs), common clusters of conditions and their impact on cost and utilization.Methods: This was a cross-sectional analysis of US financial claims data representative of the US population, including Medicare, Medicaid, and Commercial insurance claims in 2015. Outcome measures included healthcare costs and contributors; ranking of clusters of conditions according to frequency, strength of association and unsupervised (k-means) analysis; the impact of clustering on costs and contributors to costs.Results: Of 1,878,951 patients, 931,045(49.6%) had MCCs, 56.5% weighted to the US population. Mean age was 53.0 years (SD16.7); 393,121(42.20%) were male. Mean annual healthcare spending was $12,601, ranging from $4,385 (2 conditions) to $33,874 (11 conditions), with spending increasing by 22-fold for inpatient services, 6-fold for outpatient services, 4.5-fold for generic drugs, and 4.2-fold for branded drugs. Cluster ranking using the 3 methodologies yielded similar results: highest ranked clusters included metabolic syndrome (12.2% of US insured patients), age related diseases (7.7%), renal failure (5.6%), respiratory disorders (4.5%), cardiovascular disease(CVD) (4.3%), cancers (4.1–4.3%), mental health-related clusters (1.0–1.5%), and HIV/AIDS (0.2%). Highest spending was in HIV/AIDS clusters ($48,293), mental health-related clusters ($38,952–$40,637), renal disease ($38,551), and CVD ($37,155); with 89.9% of spending on outpatient and inpatient care combined, and 10.1% on medication.Conclusion and Relevance: Over 57% of insured patients in the US may have MCCs. MCC Clustering is frequent and is associated with healthcare utilization. The findings favor health system redesign toward a multiple condition approach for clusters of chronic conditions, alongside other cost-containment measures for MCCs.
The Prevalence of Cam Morphology: A Cross-Sectional Evaluation of 3,558 Cadaveric Femora
Authors: Hanzlik Shane , Riff Andrew J. , Wuerz Thomas H. , Abdulian Michael , Gurin Danielle , Nho Shane J. , Salata Michael J. 
Published: January 2021

Purpose: We sought to determine (1) the prevalence of cam deformity in the population and that of bilateral cam deformity, (2) the typical location of a cam lesion, and (3) the typical size of a cam lesion by direct visualization in cadaveric femora.Methods: Two observers inspected 3,558 human cadaveric femora from the Hamann–Todd Osteological Collection from the Cleveland Museum of Natural History. Any asphericity &gt;2 mm from the anterior femoral neck line was classified as a cam lesion. Once lesions had been inspected, the prevalence in the population, prevalence by gender, and prevalence of bilateral deformity were determined. Additionally, each lesion was measured and localized to a specific quadrant on the femoral neck based upon location of maximal deformity.Results: Cam lesions were noted in 33% of males and 20% of females. Eighty percent of patients with a cam lesion had bilateral lesions. When stratified by location of maximal deformity, 90.9% of lesions were in the anterosuperior quadrant and 9.1% were in the anteroinferior quadrants. The average lesion measured 17 mm long × 24 mm wide × 6 mm thick in men and 14 mm × 22 mm × 4 mm in women (p &lt; 0.05).Conclusions: The population prevalence of cam deformity determined by direct visualization in cadavers may be higher than has been suggested in studies utilizing imaging modalities.Level of Evidence : Level II, diagnostic study.
PENGARUH NET PROFIT MARGIN (NPM) DAN RETURN ON ASSETS (ROA) TERHADAP HARGA SAHAM DI PERUSAHAAN YANG TERDAFTAR DI JAKARTA ISLAMIC INDEKS (JII) (STUDI DI PT SEMEN INDONESIA TBK
Authors: Fitriani Siti Zaenab 
Published: January 2021

ABSTRAKReturn on Assets atau disingkat dengan ROA adalah rasio yang membagi antara laba bersih setelah pajak dengan rata-rata aset pada awal periode dan akhir periode. Rasio Net Profit Margin disebut juga dengan rasio pendapatan terhadap penjualan. Mengenai hal ini Margin laba bersih sama dengan laba bersih dibagi dengan penjualan bersih. Ini menunjukan kestabilan kesatuan untuk menghasilkan perolehan pada tingkat penjualan khusus. Rasio ini termasuk kedalam Rasio profitabilitas/keuntungan yaitu rasio yang digunakan untuk mengukur efisiensi penggunaan aktiva perusahaan aktiva perusahaan atau merupakan kemampuan suatu perusahaan untuk menghasilkan laba. Berdasarkan hasil penelitian, peneliti memperoleh kesimpulan dengan hasil pengujian hipotesis diperoleh bahwa thitung < ttabel = (0,729 < 1,8595) artinya secara parsial terdapat tidak signifikan antara Net Profit Margin terhadap Harga Saham pada PT. Semen Indonesia. Return On Assets (ROA) secara parsial berpengaruh tidak signifikan terhadap Harga Saham hal ini dibuktikan dengan hasil thitung < ttabel = (-1,400 < 1,8595). Secara simultan dengan hasil uji signifikasi atau uji F diperoleh hasil Fhitung > Ftabel = (7,227 < 4,74) artinya terdapat pengaruh signifikan antara Net Profit Margin dan Return On Assets terhadap Harga Saham pada PT. Semen Indonesia. ABSTRACTReturn on Assets or abbreviated as ROA is a ratio that divides net income after tax with the average asset at the beginning of the period and the end of the period. The Net Profit Margin Ratio is also called the ratio of income to sales. Regarding this, the net profit margin is equal to the net profit divided by net sales. This shows the stability of the unity to produce gains at a special sales level. This ratio is included in the profitability/profit ratio, which is the ratio used to measure the efficiency of the use of company assets, company assets or the ability of a company to generate profits. Based on the results of the study, researchers obtained conclusions with the results of hypothesis testing obtained that account <ttable = (0.729 <1.8595) means that part there was no significant difference between the Net Profit Margin of the Share Price at PT. Semen Indonesia. Return On Assets (ROA) partially has an insignificant effect on the Stock Price this is evidenced by the results of tcount <ttable = (-1,400 <1.8595). Simultaneously with the results of the significance test or F test results obtained Fcount> Ftable = (7.227 <4.74) means that there is a significant influence between Net Profit Margin and Return On Assets on the Share Price at PT. Semen Indonesia.
Women and the Challenges of the Future of Islamic Education
Authors: Manshur Fadlil Munawwar , Herlina N. Hani , Atoillah Ahmad Nabil 
Published: January 2021

This study seeks to elaborate on the position and function of women in the realm of Islamic education. This study uses the critical review method, a method used to interpret texts critically. The results of the study show that Muslim women in Indonesia are in fact part of Muslim women in other parts of the world. However, Indonesian Muslim women tend to have greater opportunities and chances in facing a bright future of education. Within Islamic education institutions, the viewpoint of women has shifted from a conservative view to a more egalitarian one. The oldest and largest Islamic education institution in Indonesia, namely pondok pesantren, is accustomed in using the terminology of equality and alignment relatives to gender as their educational discourse. They are not only fluent in discussing the concept of gender equality, the terminology has even become part of the practice of pondok pesantren education.