bluuebunny/crossref_metadata_2025_split huggingface dataset:
Democratisation and Institutional Development in Romania after 1989
Authors: Bharti Mukesh Shankar 
Published: March 2022

Purpose: the aim of the article is to present the institutional development and democratic setup which has been started to move forward towards economic development and the formation of welfare programmes for human development after the demise of Communist rule.
Design/Method/Approach: The article analyses how the countries had changed their policy to tie up with the European Union. Furthermore, the article discusses the Romanian political transformation and political transitions in the country after the regime changed in late 1989. The article asses the role of external actors to promote the establishment of democratic institutions. The case study method is driven by EU to strengthen the process of democratisation and political-institutional reformation according to Copenhagen criteria.
Findings: The result of the article is that what extent the democratisation process has been successful ever inclusion to the European Union.
Paper type: theoretical.
Substrate Stiffness Determines the Establishment of Apical-Basal Polarization in Renal Epithelial Cells but Not in Tubuloid-Derived Cells
Authors: Hagelaars Maria J. , Yousef Yengej Fjodor A. , Verhaar Marianne C. , Rookmaaker Maarten B. , Loerakker Sandra , Bouten Carlijn V. C. 
Published: March 2022

Mechanical guidance of tissue morphogenesis is an emerging method of regenerative medicine that can be employed to steer functional kidney architecture for the purpose of bioartificial kidney design or renal tissue engineering strategies. In kidney morphogenesis, apical-basal polarization of renal epithelial cells is paramount for tubule formation and subsequent tissue functions like excretion and resorption. In kidney epithelium, polarization is initiated by integrin-mediated cell-matrix adhesion at the cell membrane. Cellular mechanobiology research has indicated that this integrin-mediated adhesion is responsive to matrix stiffness, raising the possibility to use matrix stiffness as a handle to steer cell polarization. Herein, we evaluate apical-basal polarization in response to 2D substates of different stiffness (1, 10, 50 kPa and glass) in Madin Darby Canine Kidney cells (MDCKs), a classic canine-derived cell model of epithelial polarization, and in tubuloid-derived cells, established from human primary cells derived from adult kidney tissue. Our results show that sub-physiological (1 kPa) substrate stiffness with low integrin-based adhesion induces polarization in MDCKs, while MDCKs on supraphysiological (&gt;10 kPa) stiffness remain unpolarized. Inhibition of integrin, indeed, allows for polarization on the supraphysiological substrates, suggesting that increased cellular adhesion on stiff substrates opposes polarization. In contrast, tubuloid-derived cells do not establish apical-basal polarization on 2D substrates, irrespective of substrate stiffness, despite their ability to polarize in 3D environments. Further analysis implies that the 2D cultured tubuloid-derived cells have a diminished mechanosensitive capacity when presented with different substrate stiffnesses due to immature focal adhesions and the absence of a connection between focal adhesions and the cytoskeleton. Overall, this study demonstrates that apical-basal polarization is a complex process, where cell type, the extracellular environment, and both the mechanical and chemical aspects in cell-matrix interactions performed by integrins play a role.
Behavior of Magnetically-Driven Concrete (MDC) Filled Double-Skin GFRP Tubes (CFDGT) Under Axial Compression
Authors: Xie Xian-Song , Chen Ju , Wang Jun , Liu Cheng-Bin 
Published: March 2022

In order to study the axial compression behavior of magnetically-driven concrete (MDC) filled double-skin GFRP tubes (CFDGT), the axial compression test was conducted on eight columns (the length of columns ranged from 1,000 mm to 3,000 mm). For the MDC, a magnetic vibration device was established to vibrate the MDC, and two series of MDC (concrete with and without vibration) were adopted to investigate the vibration effect, research results showed that the concrete between two circular GFRP tubes could be effectively vibrated by the magnetic force. For the CFDGT columns with MDC, the load-displacement curves, load-strain curves, failure modes and ultimate loads of tested columns were obtained. After the axial compression test, a finite element model was proposed to predict the axial compression behavior and carry out parametric analysis. The design equations for the ultimate load of CFDGTs were derived from the finite element results, comparison results showed that the design equations can predict the ultimate load of CFDGT columns accurately and conservatively, and the maximum calculation error was controlled within 10%.
Rapamycin and Resveratrol Modulate the Gliotic and Pro-Angiogenic Response in Müller Glial Cells Under Hypoxia
Authors: Subirada Paula V. , Vaglienti María V. , Joray Mariana B. , Paz María C. , Barcelona Pablo F. , Sánchez María C. 
Published: March 2022

Hypoxia and hypoxia-reoxygenation are frequently developed through the course of many retinal diseases of different etiologies. Müller glial cells (MGCs), together with microglia and astrocytes, participate firstly in response to the injury and later in the repair of tissue damage. New pharmacological strategies tend to modulate MGCs ability to induce angiogenesis and gliosis in order to accelerate the recovery stage. In this article, we investigated the variation in autophagy flux under hypoxia during 4 h, employing both gas culture chamber (1% O2) and chemical (CoCl2) hypoxia, and also in hypoxia-reoxygenation. Then, we delineated a strategy to induce autophagy with Rapamycin and Resveratrol and analysed the gliotic and pro-angiogenic response of MGCs under hypoxic conditions. Our results showed an increase in LC3B II and p62 protein levels after both hypoxic exposure respect to normoxia. Moreover, 1 h of reoxygenation after gas hypoxia upregulated LC3B II levels respect to hypoxia although a decreased cell survival was observed. Exposure to low oxygen levels increased the protein expression of the glial fibrillary acid protein (GFAP) in MGCs, whereas Vimentin levels remained constant. In our experimental conditions, Rapamycin but not Resveratrol decreased GFAP protein levels in hypoxia. Finally, supernatants of MGCs incubated in hypoxic conditions and in presence of the autophagy inductors inhibited endothelial cells (ECs) tubulogenesis. In agreement with these results, reduced expression of vascular endothelial growth factor (VEGF) mRNA was observed in MGCs with Rapamycin, whereas pigment epithelium-derived factor (PEDF) mRNA levels significantly increased in MGCs incubated with Resveratrol. In conclusion, this research provides evidence about the variation of autophagy flux under hypoxia and hypoxia-reoxygenation as a protective mechanism activated in response to the injury. In addition, beneficial effects were observed with Rapamycin treatment as it decreased the gliotic response and prevented the development of newly formed blood vessels.
Arterial Stiffness in a Cohort of Young People Living With Perinatal HIV and HIV Negative Young People in England
Authors: Mellin J. , Le Prevost M. , Kenny J. , Sturgeon K. , Thompson L. C. , Foster C. , Kessler H. H. , Goswami Nandu , Klein N. , Judd A. , Castro H. 
Published: March 2022

BackgroundAntiretroviral therapy (ART) has increased life expectancy and consequently the risk of cardiovascular disease (CVD) in adults living with HIV. We investigated the levels and predictors of arterial stiffness in young people (YP) living with perinatal HIV (PHIV) and HIV negative YP in the Adolescents and Adults Living with Perinatal HIV (AALPHI) study.MethodsAALPHI was a prospective study evaluating the impact of HIV infection and exposure to ART on YP living with PHIV (aged 13–21 years) who had known their HIV status for at least 6 months, and HIV negative YP (aged 13–23 years) who either had a sibling, friend or parent living with HIV. Participants were enrolled from HIV clinics and community services in England. Two hundred and thirteen PHIV and 65 HIV negative YP (42% siblings of PHIV) had pulse wave velocity (PWV) measurements taken (Vicorder software) from the supra-sternal notch to the middle of the thigh cuff, at their second interview in the study between 2015 and 2017. Average PWV was calculated from the three closest readings (≥3 and ≤ 12 m/s) within 0.6 m/s of each other. Linear regression examined predictors of higher (worse) PWV, including age, sex, HIV status and height as a priori, ethnicity, born outside UK/Ireland, alcohol/nicotine/drug use, weight, waist-to-hip-ratio, mean arterial pressure (MAP), caffeine 2 h before PWV and nicotine on day of PWV. A separate PHIV model included CD4, viral load, years taking ART and ART regimen.FindingsOne hundred and twenty eight (60%) PHIV and 45 (69%) HIV negative YP were female (p = 0.18), with median (IQR) age 18 (16, 20) and 18 (16, 21) years (p = 0.48) respectively. Most PHIV were taking a combination of three ART drugs from two classes. There was a trend toward higher (worse) mean PWV in the PHIV group than the HIV negative group [unvariable analysis 6.15 (SD 0.83) m/s vs. 5.93 (0.70) m/s, respectively, unadjusted p = 0.058], which was statistically significant in the multivariable analysis [adjusted p (ap) = 0.020]. In multivariable analysis being male (ap = 0.002), older age (ap &lt; 0.001), higher MAP (ap &lt; 0.001) and nicotine use on day of measurement (ap = 0.001) were also predictors of higher PWV. The predictors were the same in the PHIV model.InterpretationBy late adolescence PHIV had worse PWV in comparison to HIV negative peers, and traditional risk factors for CVD (higher arterial pressure, being male and older age) were associated with higher PWV values. Regular detailed monitoring of cardiovascular risk factors should become standard of care for every young person with PHIV worldwide.
Earthquake Forecast as a Machine Learning Problem for Imbalanced Datasets: Example of Georgia, Caucasus
Authors: Chelidze Tamaz , Kiria Tengiz , Melikadze George , Jimsheladze Tamar , Kobzev Gennady 
Published: March 2022

In this article, we considered the problem of M≥3 earthquake (EQ) forecasting (hindcasting) using a machine learning (ML) approach, using experimental (training) time series on monitoring water-level variations in deep wells as well as geomagnetic and tidal time series in Georgia (Caucasus). For such magnitudes’, the number of “seismic” to “aseismic” days in Georgia is approximately 1:5 and the dataset is close to the balanced one. However, the problem of forecast is practically important for stronger events—say, events of M≥3.5—which means that the learning dataset of Georgia became more imbalanced: the ratio of seismic to aseismic days for in Georgia reaches the values of the order of 1:20 and more. In this case, some accepted ML classification measures, such as accuracy leads to wrong predictions due to a large number of true negative cases. As a result, the minority class, here—seismically active periods—is ignored at all. We applied specific measures to avoid the imbalance effect and exclude the overfitting possibility. After regularization (balancing) of the training data, we build the confusion matrix and performed receiver operating classification in order to forecast the next day probability of M≥3.5 earthquake occurrence. We found that the Matthews’ correlation coefficient (MCC) is the measure, which gives good results even if the negative and positive classes are of very different sizes. Application of MCC to observed geophysical data gives a good forecast of the next day M≥3.5 seismic event probability of the order of 0.8. After randomization of EQ dates in the training dataset, the Matthews’ coefficient efficiency decreases to 0.17.
Adjuvant Probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in Patients With Type 1 Diabetes Mellitus
Authors: Wang Chung-Hsing , Yen Hung-Rong , Lu Wen-Li , Ho Hsieh-Hsun , Lin Wen-Yang , Kuo Yi-Wei , Huang Yen-Yu , Tsai Shin-Yu , Lin Hung-Chih 
Published: March 2022

IntroductionType 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS).Research Design and MethodsA randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strainsLactobacillus salivariussubsp.saliciniusAP-32,L. johnsoniiMH-68, andBifidobacterium animalissubsp.lactisCP-9 daily for 6 months, and 29 patients were administered insulin therapy without extra probiotic supplement as placebo group. The variations of fasting blood glucose and HbA1c in these patients were analyzed. In addition, serum levels of inflammatory cytokines and anti-inflammatory cytokine were assessed using enzyme-linked immunosorbent assay. Patients’ stool microbiota were all subjects to NGS analysis.ResultsNGS data showed elevated populations ofBifidobacterium animalis, Akkermansia muciniphilaandLactobacillus salivariusin the gut of patients with T1DM who were taking probiotics. Patients with T1DM who were administered probiotics showed significantly reduced fasting blood glucose levels compared with the before-intervention levels. The HbA1c levels of the patients also improved after administration of probiotics. The concentrations of IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced and were associated with an increased TGF-β1 expression after probiotic intervention. The persistence effect of glycemic control and immunomodulation were observed even 3 months after discontinuation of the probiotics.ConclusionsHere, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03880760.
pH-Responsive Amphoteric p (APTMACl-co-AMPS) Hydrogel as Effective Multiple Dye Sponge Network From Aqueous Media
Authors: Demirci Sahin , Ari Betul , Aktas Nahit , Sahiner Nurettin 
Published: March 2022

Here, the cationic poly (3-acrylamidepropyl trimethyl ammonium chloride) [p (APTMACl)], anionic poly (2-acrylamido-2methylpropane sulfonic acid) [p (AMPS)], and amphoteric poly (APTMACl-co-AMPS) hydrogels were prepared via free-radical polymerization techniques as pH-sensitive hydrogels. The prepared systems were used in methylene blue (MB), and Eosin Y (EY) removal from aqueous media. HCl-treated p (APTMACl-co-AMPS) hydrogels prepared in 1:3 mol ratio adsorbed higher amount of MB and EY from their corresponding 50 ml 50 ppm aqueous solutions that are 47.5 ± 0.9, and 10.7 ± 0.1 mg/g, respectively. Also, the adsorbed amount of MB and EY by HCl-treated p (APTMACl-co-AMPS) hydrogels decreased with the increase in the medium pH from 3.0 to 9.0. It was also observed that HCl-treated p (APTMACl-co-AMPS)-3 hydrogels removed 39.2 ± 0.2, and 28.1 ± 1.0 mg/g MB and EY dyes simultaneously from their corresponding 50 ml 50 ppm aqueous mixture solutions. MB and EY adsorption by HCl-treated p (APTMACl-co-AMPS)-3 hydrogels were found to abide by pseudo-first-order adsorption kinetics. Moreover, MB adsorption by HCl-treated p (APTMACl-co-AMPS) hydrogels were found to fit with Freundlich, EY adsorption fit with Langmuir isotherms. The distribution coefficient values of HCl-treated p (APTMACl-co-AMPS) hydrogels were calculated as 3.7 ± 0.1 and 1.3 ± 0.1 for MB and EY, respectively. The calculated selectivity coefficient value showed that HCl-treated p (APTMACl-co-AMPS) hydrogels are at least 3-fold higher selective to MB than EY.
Frequency and Factors Associated With Adverse Events Among Multi-Drug Resistant Tuberculosis Patients in Pakistan: A Retrospective Study
Authors: Atif Muhammad , Ahmed Waqar , Nouman Iqbal Muhammad , Ahmad Nafees , Ahmad Wajiha , Malik Iram , Al-Worafi Yaser Mohammed 
Published: March 2022

BackgroundTreatment of multi-drug resistant tuberculosis (MDR-TB) for a prolonged period with comparatively less effective and more toxic second-line anti-TB drugs is associated with greater incidence of adverse events.Study aimThis study aimed to evaluate the frequency and factors associated with occurrence of adverse events among patients with MDR-TB attending the Bahawal Victoria Hospital, Bahawalpur, Pakistan.Study designThis retrospective study included all patients with MDR-TB who were registered and treated at the study site between June 2014 and December 2016 and had their treatment outcomes available at the time of data collection (i.e., November 2018).Measures and outcomesThe Electronic Nominal Record System (ERNS) records, medical charts of patients, and laboratory reports were reviewed to obtain the data. Adverse events were reported as per the standard criteria recommended by the WHO. Multivariate binary logistic regression was used to find the independent factors associated with the occurrence of adverse events.ResultsA total of 179 patients with MDR-TB were included in the final analysis. Out of these, 114 (63.7%) patients experienced at least one adverse event during the course of their treatment. Depression was the most common adverse events (33%), followed by nausea and vomiting (27.4%) and arthralgia (27.4%). The factors associated with the occurrence of adverse events included presence of comorbidity (adjusted odds ratio [AOR] 2.951; 95% CI 1.423, 6.118) and being employed (AOR 3.445; 95% CI 1.188, 9.993).ConclusionAdverse events were prevalent in this cohort, however, resolved with the effective management approaches. Patients with identified factors for occurrence of adverse events need special attention and enhanced clinical management.
Clinical Outcomes in Maximum Tolerated Medical Therapy in Penetrating Keratoplasty for Bullous Keratopathy
Authors: Wy Seoyoung , Kim Young Kook , Jeoung Jin Wook , Kim Mee Kum 
Published: March 2022

PurposeTo compare the clinical outcomes of maximum tolerated medical therapy (MTMT) in patients with penetrating keratoplasty (PKP) with those of Ahmed glaucoma valve (AGV) implantation.MethodsThe medical records were retrospectively reviewed in patients who had undergone PKP for bullous keratopathy and were treated with MTMT or AGV implantation for the management of glaucoma. A total of 18 bullous keratopathic patients were investigated between January 2010 and February 2017: 9 patients treated with MTMT and 9 patients treated with AGV implantation. Non-corrected visual acuity (NCVA), intraocular pressure (IOP), endothelial cell density (ECD), hexagonality, coefficient of variation (CV), central corneal thickness (CCT), median survival time of the graft, and the presence of epithelial keratopathy were compared between the groups at each time point or between baseline and after treatment of glaucoma in each group.ResultsThere were no significant differences in the visual acuity and corneal thickness between the two groups or within each group over time. Both groups showed a significant reduction in IOP compared with the baseline IOP, and IOP reductions were greater in the AGV group than in the MTMT group (p = 0.040). Significant ECD reductions were found in each group between the baseline and 6 months (p = 0.008 in the MTMT group, p = 0.015 in the AGV group); however, no differences were found between the two groups until 12 months. The significant hexagonality reduction was found in the AGV group between the baseline and 12 months (p = 0.018). The median survival time showed no significant difference in the survival analysis.ConclusionsMaximum tolerated medical therapy in penetrating keratoplasty for bullous keratopathy seems to similarly affect the endothelial cell density or graft survival when compared with at least 12 month-followed Ahmed glaucoma valve implantation.
Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer
Authors: Shi Zhan , Yang Ju , Kong Weiwei , Qiu Xin , Lu Changchang , Liu Juan , Liu Baorui , Du Juan 
Published: March 2022

Background and PurposeA phase 2 study LAPACT indicated nab-paclitaxel plus gemcitabine (AG) improved outcomes of patients with locally advanced pancreatic cancer (LAPC). Conventional radiotherapy failed to show benefit, indicating high dose to volume with high risk of recurrence is needed. The high dose can be delivered through hypofractionated tomotherapy with simultaneous integrated boost (SIB). However, there is a lack of such prospective trials and more data are needed to validate the role of AG plus hypofractionated tomotherapy with SIB in patients with LAPC.Materials and MethodsPatients with LAPC receiving AG plus tomotherapy at the Nanjing Drum Tower Hospital between 2018 and 2021 were retrospectively analyzed. The treatment was scheduled as follows: nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 on days 1 and 8 every three weeks for at least two cycles, followed by hypofractionated tomotherapy with SIB (high dose field: 50 Gy/10 fractions, the remainder: 30 Gy/10 fractions). Then patients were given AG until intolerance or disease progression.ResultsOverall, 22 patients completing the chemoradiotherapy were included. The median follow-up was 15.2 months. After the chemoradiotherapy, 5 patients achieved a partial response (PR), 15 had a stable disease (SD), and another 2 patients were with progressive disease (PD). The median progression-free survival (PFS) and overall survival (OS) were 12.8 months (95% confidence interval [CI] 4.3–21.3 months) and 16.3 months (95% CI 10.9–21.6 months), respectively. The optimal carbohydrate antigen (CA) 19-9 response and chemotherapy cycles ≥6 were correlated with favorable PFS and OS. The most common recurrent pattern was peritoneal dissemination (22.7%) and the locoregional recurrence rate was relatively low (4.5%). Treatments were well-tolerated. The most common grade ≥3 adverse event was thrombocytopenia (13.6%).ConclusionThis study demonstrated the feasibility of AG followed by hypofractionated tomotherapy with SIB in patients with LAPC. The hypofractionated tomotherapy with SIB was safe and showed high local control rate. Further study with a larger population to validate our data is underway.