bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derivation and Characterisation of Endothelial Cells from Patients with Chronic Thromboembolic Pulmonary Hypertension.
Authors: Tura-Ceide Olga , Smolders Valérie F.E.D. , Aventin Núria , Morén Constanza , Guitart-Mampel Mariona , Blanco Isabel , Piccari Lucilla , Osorio Jeisson , Rodriguez Cristina , Rigol Montserrat , Solanes Núria , Malandrino Andrea , Kurakula Kondababu , Goumans Marie Jose , Quax Paul , Peinado Victor I. , Castellà Manuel , Barberà Joan Albert 
Published: April 2021

Abstract
Rationale: Pulmonary endarterectomy (PEA) resected material offers a unique opportunity to develop an in vitro endothelial cell model of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to comprehensively analyze the endothelial function, molecular signature and mitochondrial profile of CTEPH-derived endothelial cells to better understand the pathophysiological mechanisms of endothelial dysfunction behind CTEPH, and to identify potential novel targets for the prevention and treatment of the disease. Methods: Isolated cells from specimens obtained at PEA (CTEPH-EC), were characterized based on morphology, phenotype and functional analyses (in vitro and in vivo tubule formation, proliferation, apoptosis, and migration). Mitochondrial content, morphology, and dynamics, as well as high-resolution respirometry and oxidative stress, were also studied. Results: CTEPH-EC displayed a hyperproliferative phenotype with an increase expression of adhesion molecules and a decreased apoptosis, eNOS activity, migration capacity and reduced angiogenic capacity in vitro and in vivo compared to healthy endothelial cells. CTEPH-EC presented altered mitochondrial dynamics, increased mitochondrial respiration and an unbalanced production of reactive oxygen species and antioxidants. Conclusions: Our study is the foremost comprehensive investigation of CTEPH-EC. Modulation of redox, mitochondrial homeostasis and adhesion molecule overexpression arise as novel targets and biomarkers in CTEPH.
Identifying women with gestational diabetes based on maternal characteristics: An analysis of four Norwegian prospective studies
Authors: Sletner Line , Jenum Anne Karen , Øverby Nina Cecilie , Stafne Signe Nilssen , Lekva Tove , Pripp Are Hugo , Sagedal Linda Reme , rai Anam Shakil 
Published: April 2021

Abstract
Background There is still no worldwide agreement on the best diagnostic thresholds to define gestational diabetes (GDM) or the optimal approach for identifying women with GDM. Should all pregnant women perform an oral glucose tolerance test (OGTT) or can easily available maternal characteristics, such as age, BMI and ethnicity, indicate which women to test? The aim of this study was to assess the prevalence of GDM by three diagnostic criteria and the predictive accuracy of commonly used risk factors.Methods We merged data from four Norwegian cohorts (2002–2013), encompassing 2981 women with complete results from a universally offered OGTT. Prevalences were estimated based on the following diagnostic criteria: 1999WHO (fasting plasma glucose (FPG) ≥ 7.0 or 2-h glucose ≥ 7.8 mmol/L), 2013WHO (FPG ≥ 5.1 or 2-h glucose ≥ 8.5 mmol/L), and 2017Norwegian (FPG ≥ 5.3 or 2-h glucose ≥ 9 mmol/L). Multiple logistic regression models examined associations between GDM and maternal factors. We applied the 2013WHO and 2017Norwegian criteria to evaluate the performance of different thresholds of age and BMI.Results The prevalence of GDM was 10.7%, 16.9% and 10.3%, applying the 1999WHO, 2013WHO, and the 2017Norwegian criteria, respectively, but was higher for women with non-European background when compared to European women (14.5 vs 10.2%, 37.7 vs 13.8% and 27.0 vs 7.8%). While advancing age and elevated BMI increased the risk of GDM, no risk factors, isolated or in combination, could identify more than 80% of women with GDM by the latter two diagnostic criteria, unless at least 70–80% of women were offered an OGTT. Using the 2017Norwegian criteria, the combination “age ≥ 25 years or BMI ≥ 25 kg/m²” achieved the highest sensitivity (96.5%) with an OGTT required for 93% of European women. The predictive accuracy of risk factors for identifying GDM was even lower for non-European women.Conclusions The prevalence of GDM was similar using the 1999WHO and 2017Norwegian criteria, but substantially higher with the 2013WHO criteria, in particular for ethnic non-European women. Using clinical risk factors such as age and BMI is a poor pre-diagnostic screening method, as this approach failed to identify a substantial proportion of women with GDM unless at least 70–80% were tested.
Tanshinone I Exerts Cardiovascular Protective Effects in Vivo and in Vitro Through Inhibiting Necroptosis via Akt/nrf2 Signaling Pathway
Authors: Zhuo Youqiong , Yuan Renyikun , Chen Xinxin , He Jia , Chen Yangling , Zhang Chenwei , Sun Kaili , Yang Shilin , Liu Zhenjie , Gao Hongwei 
Published: April 2021

Abstract
BackgroundTanshinone I (TI) is a primary component of Salvia miltiorrhiza Bunge (Danshen), which confers a favorable role in a variety of pharmacological activities including cardiovascular protection. However, the exact mechanism of the cardiovascular protection activity of TI remains to be illustrated. In this study, the cardiovascular protective effect and its mechanism of TI were investigated.MethodsIn this study, tert-butyl hydroperoxide (t-BHP)-stimulated H9c2 cells model was employed to investigate the protective effect in vitro. The cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) kit. The reactive-oxygen-species (ROS) level and mitochondrial membrane potential (MMP) were investigated by the flow cytometry and JC-1 assay, respectively. While in vivo experiment, the cardiovascular protective effect of TI was determined by using myocardial ischemia-reperfusion (MI/R) model including hematoxylin-eosin (H&E) staining assay and determination of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release were detected by Enzyme-linked immunosorbent assay (ELISA). All related protein expression was determined by western blotting.ResultsOur data demonstrated that TI pretreatment attenuated t-BHP- and MI/R injury-induced necroptosis by inhibiting the expression of p-RIP1, p-RIP3, and p-MLKL. TI activated the Akt/Nrf2 pathway to promote the expression of antioxidant-related proteins such as phosphorylation of Akt, nuclear factor erythroid 2 related factor 2 (Nrf2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1) expression in t-BHP-stimulated H9c2 cells. TI relieved oxidative stress by mitigating ROS generation and reversing MMP loss. In vivo experiment, TI made electrocardiograph (ECG) recovery better and lessened the degree of myocardial tissue damage. The counts of white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), and the release of TNF-α and IL-6 were reversed by TI treatment. SOD level was increased, while MDA level was decreased by TI treatment.ConclusionCollectively, our findings indicated that TI exerted cardiovascular protective activities in vitro and in vivo through suppressing RIP1/RIP3/MLKL and activating Akt/Nrf2 signaling pathways, which could be developed into a cardiovascular protective agent.
The Mechanism by Which LiCl&nbsp;Attenuates the Impaired Ability of Learning and Memory of APP/PS1 Double Transgenic Mice May Involve Elevating the Expression of a7 Nicotinic Acetylcholine Receptors via Regulation of the Wnt/β-catenin Pathway
Authors: Jie Xiang , Yan Ran Long , Xiao Zeng Xiao , Wen He Wen , Yi Xu , Kun Cao , Ting Dong Yang , Lan Qi Xiao , Feng Yu Wen , Yan Xiao , Jun He , Guan Zhi-Zhong 
Published: April 2021

Abstract
BackgroundWe examined the mechanism by which lithium chloride (LiCl) attenuates the impaired learning and memory of APP/PS1 double transgenic (APP/PS1) mice. MethodsSix- or twelve-month-old APP/PS1 and wild-type (WT) mice were divided randomly into 4 groups: WT, WT+Li (100 mg LiCl/kg body weight, gavage once daily), APP/PS1 and APP/PS1+Li. Primary rat hippocampal neurons were exposed to β-amyloid peptide oligomers (AβOs), LiCl and/or XAV939 (inhibitor of Wnt/β-catenin) or transfected with small interfering RNA against the β-catenin gene. Phosphor-glycogen synthase kinase-3β (GSK3β) (ser9), total GSK3β, β-catenin, cyclin D1, and α7 nAChR protein and mRNA were quantified by Western blotting or real-time PCR, respectively; senile plaques and α7 protein by immunohistochemical or immunofluorescent staining; Aβ 42 by ELISA; and cell viability by CCK8. Learning and memory were assessed utilizing the Morris water maze test. ResultsIn the brains of APP/PS1 mice, the level of Aβ was increased and those of α7 nAChR, phosphor-GSK3β (ser9), β-catenin, and cyclin D1 (at the protein and/or mRNA level) reduced. Treatment with LiCl for 2 months at 4 or 10 months of age attenuated all of these effects. Similar changes in the levels of these proteins were observed in primary neurons exposed to AβOs and these effects were attenuated by LiCl and aggravated by XAV939. Inhibition of β-catenin expression lowered the level of α7 nAChR protein in these cells. ConclusionLiCl attenuates the impaired ability of learning and memory of APP/PS1 mice via a mechanism that might involve elevation of the level of α7 nAChR as a result of altered Wnt/β-catenin signaling.
Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria
Authors: Gul Saba , Ribeiro-Gomes Flavia L. , Moreira Aline S. , Sanches Guilherme S. , Conceição Fabiana G. , Daniel-Ribeiro Cláudio Tadeu , Ackerman Hans C. , Carvalho Leonardo J. M. 
Published: April 2021

Abstract
Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 µL of whole blood along with 20 mg/kg of artemether. ECM mice showed severe thrombocytopenia and decreases in hematocrit. Artemether treatment markedly aggravated anemia within 24 hours. Whole blood administration significantly prevented further drop in hematocrit and partially restored the platelet count. Increased levels of plasma angiopoietin-2 (Ang-2) remained high 24 hours after artemether treatment but returned to normal levels 24 hours after blood transfusion, indicating reversal to quiescence. Ang-1 was depleted in ECM mice and levels were not restored by any treatment. Blood transfusion prevented the aggravation of the breakdown of blood brain barrier after artemether treatment and decreased spleen congestion without affecting splenic lymphocyte populations. Critically, blood transfusion resulted in markedly improved survival of mice with ECM (75.9% compared to 50.9% receiving artemether only). These findings indicate that whole blood transfusion can be an effective adjuvant therapy for cerebral malaria.
A Cross-Sectional Study of COVID-19-Related Bullying in a Sample of Lebanese Adults: Scale Validation, Correlates, and Mediating Effect of Fear and Anxiety
Authors: Haddad Chadia , Sacre Hala , Malhab Sandrella Bou , Malaeb Diana , Saadeh Danielle , Tayeh Christine Abou , Salameh Pascale 
Published: April 2021

Abstract
Background: The COVID-19 pandemic has led to prolonged exposure to stress and anxiety, raising concerns about a large spectrum of psychological side effects. The primary objective of the study was to validate the COVID-19 Bullying Scale (CBS-11). The second objective was to explore factors associated with COVID-19-related bullying and evaluate the mediating effect of fear and anxiety between knowledge and COVID-19-related bullying.Methods: A cross-sectional online survey conducted between December 20, 2020, and January 5, 2021, involved 405 Lebanese adults recruited using the snowball sampling technique. The CBS-11, an 11-item tool specially created for this study, was used to measure bullying behaviors towards COVID-19 patients.Results: All items of CBS-11 converged over a 1-factor solution with an eigenvalue over 1, accounting for a variance of 75.16%. The scale has a high Cronbach’s alpha (0.974), indicating excellent reliability. A positive correlation was found between the COVID-19 bullying scale and fear, anxiety, and stigma discrimination. The logistic regression showed that higher fear of COVID-19 (ORa=1.04), a positive attitude toward COVID-19 preventive measures and hygiene recommendations (ORa=1.18), higher stigma discrimination scores (ORa=1.09), and having a health professional family member (ORa=2.42) were significantly associated with bullying. Conclusion: Our main findings show that CBS-11 could be an efficient tool to measure bullying behaviors toward COVID-19 patients. Stigma discrimination and fear from COVID-19 were associated with higher bullying attitudes. Future prospective studies are needed to understand better the factors related to bullying among adults during a pandemic, such as COVID-19.
Recurring Severe Injection-related Infections in People Who Inject Drugs and the Need for Safe Injection Sites in Spain
Authors: Valencia Jorge , Troya Jesús , Lazarus Jeffrey V , Cuevas Guillermo , Alvaro-Meca Alejandro , Torres-Macho Juan , Gardeta Carlos , Lozano David , Moreno Santiago , Ryan Pablo 
Published: April 2021

Abstract
Background and aims: An estimated 68,297 people with opioid use disorder engage in opioid agonist therapy (OAT) in Spain. We aimed to calculate the incidence of severe injection-related infections in people who inject drugs (PWID) engaged in OAT in a harm reduction setting without a safe injection site (SCS).Methods: A retrospective cohort study was performed in PWID engaged in OAT and in a mobile harm reduction unit to identify who was admitted to a referral hospital for any severe injection-related infections between 1 Jan 2016 and 31 Dec 2019. A Cox proportional hazard regression analysis was used to assess factors associated with any severe injection-related infection.Results: 237 PWID engaged in OAT were included. After a median follow-up of 5.5 months (IQR 1.3–22.7), a total of 104 episodes of severe injection-related infections occurred in 56 individuals, and admission for a second event occurred in 35.7% of this same group. The incidence density of any type of severe injection-related infection was 26.8 (20.2–34.8) episodes per 100 PY, and the incidence density of complicated skin and soft tissue infections (SSTIs) that required hospital admission was 20.4 (15.0–27.3) episodes per 100 PY. Fifty-six (53.8%) of all the episodes were patient-directed discharge (PDD), and people who had two or more hospital admissions had a higher PDD frequency.Conclusion: Severe injection-related infections remain highly prevalent among PWID cared for in a harm reduction setting without a SCS. PDD were more frequent in higher-risk individuals who presented two or more hospital readmissions.
How Spectral Properties and Machine Learning Can Categorize Twin Species - Based on Diachrysia Genus
Authors: Dyba Krzysztof , Wąsala Roman , Piekarczyk Jan , Gabała Elżbieta , Gawlak Magdalena , Jasiewicz Jarosław , Ratajkiewicz Henryk 
Published: April 2021

Abstract
Confirmation of distinctiveness or taxonomic affinity awaits new evidence in many twin species. In our work we used noninvasive point reflectance spectroscopy in the range from 400 to 2100 nm coupled with machine learning to study scales on the brown and golden iridescent areas on the dorsal side of the forewing of Diachrysia chrysitis and D. stenochrysis. The basis for the study a statistically significant collection of 95 specimens gathered during 23 years in Poland. The numerical part of an experiment included two independent discriminant analyses: stochastic and deterministic. The more sensitive stochastic approach achieved average compliance with the species classification made by entomologists at the level of 99-100%. It demonstrated high stability against the different configurations of training and validation sets, hence strong predictors of Diachrysia siblings distinctiveness. Both methods resulted in the same small set of relevant features, where minimal fully discriminating subsets of wavelengths were three for glass scales on the golden area and four for the brown. The differences between species in scales primarily concern their major components and ultrastructure. In melanin-absent glass scales, this is mainly chitin configuration, while in melanin-present brown scales, melanin reveals as an additional factor.
Application of a Lateral Intertubercular Sulcus Plate in the Treatment of Proximal Humeral Fractures: a Finite Element Analysis and Example in Clinical Practice
Authors: Li Dong , Lv WenXue , Chen WenMing , Meng Jing , Liu Song , Duan ZongKang , Yu Bo 
Published: April 2021

Abstract
Background: Inversion deformities caused by insufficient medial support are especially common when the PHILOS locking plate is used to treat proximal humeral fractures. Using finite element analysis, the present study aimed to compare the biomechanical properties of a PHILOS locking plate (PLP) and a PHILOS plate combined with a lateral intertubercular sulcus plate (PLP-LSP) in the fixation of proximal humeral fractures with loss of the medial column. We also present representative results for a 69-year-old female patient with a comminuted fracture of the proximal right humerus (Neer type four-part fracture) who underwent successful surgical treatment with a PHILOS plate combined with an auxiliary lateral intertubercular sulcus plate. Methods: After creating a three-dimensional finite element model of proximal humeral fracture with loss of the medial column, three implant models were established. A full-screw PHILOS plate (PLP) was used in Group A, while a PHILOS plate lacking medial screw support and an auxiliary plate were used in Group B (MPLP-LSP). A full-screw PHILOS plate and auxiliary plate were used in Group C (PLP-LSP). The three fixation models were applied to the proximal humerus fracture model, following which horizontal, compressive, and rotational loads were applied to the humerus model. We evaluated the structural stiffness and stress distribution of the implant and compared displacement and angle changes among the three models. Results: Displacement and angle changes were smallest in Group C (PLP-LSP). The implant model used in Group C also had the highest structural rigidity, endured less von Misses stress than the other two models , and had the strongest stability. In our clinical case, X-ray and computed tomography images obtained 3 months after the operation indicated that the fracture had healed, with good positioning of internal fixation and good functional recovery.Conclusion: A lateral intertubercular sulcus plate placed at the internodal grove not only aids in anatomical reduction but also provides effective lateral and medial support, thereby reducing stress on the PHILOS plate and providing better stability in patients with proximal humeral fractures.
Magnitude of Long-acting and Permanent Family Planning Practice and Its Factors Among Contraceptive Users: A Cross-sectional Study
Authors: Wondyfraw Alemu Abebe , Kassaw Nigussie Assefa 
Published: April 2021

Abstract
Background: Poor contraceptive utilization increases the risk of unintended pregnancies that could results in complications and mortalities among women and children. To circumvent these adverse health outcomes, long-acting and permanent contraceptive methods are the most effective methods. This study explored the magnitude and associated factors of long-acting and permanent family planning methods utilization among current family planning users largely on the rural women of Ethiopia. Methods: The study was a facility-based cross-sectional study design. The respondents were randomly selected in Amhara region, Ethiopia. The data were entered into EPI-INFO version 7.0, cleaned, and analyzed in SPSS version 24. Descriptive statistics were done. Bivariate and multivariable logistic regression models were used to identify the factors associated with the utilization of long-acting and permanent family planning methods. Results: The total numbers of respondents were 356. The prevalence of long-acting and permanent family planning methods among current family planning users was 32.3%. The mean age of participants was 30.1±7.67 (SD) years. Almost all (94.4%) were Orthodox Christian followers and most of the respondents (91.0%) married. Nearly half of the respondents (45.2%) were illiterate and above half of the respondents (55.3%) were housewives. The odds of long-acting and permanent family planning methods utilization were statistically significant among women aged 25-34 years [AOR=5.10; 95% CI: (1.48, 17.59)], women who completed secondary education [AOR=4.16; 95% CI: (1.32, 13.10)], women who had a positive attitude [AOR=3.05; 95% CI: (1.45, 6.43)], and women satisfied with facility care [AOR=2.08; 95% CI: (1.01, 4.31)]. Common reasons for low use of long-acting and permanent family planning methods were preference for short-acting contraceptives, fear of side effects, and method misconception. Conclusion: The utilization of long-acting and permanent family planning method was low. Factors and common reasons for low utilization of long-acting and permanent family planning methods among women who were current family planning users were identified. Therefore, we suggest the need to provide continuous education and awareness creation towards long-acting and permanent family planning methods. Unequivocally, enabling work environments, staff service deliveries and client service satisfaction are paramount important improve the coverage.
Increased uptake of 68Ga-DOTA-FAPI-04 in bones and joints: metastases and beyond
Authors: Qin Chunxia , Song Yangmeihui , Liu Xi , Gai Yongkang , Liu Qingyao , Ruan Weiwei , Liu Fang , Hu Fan , Lan Xiaoli 
Published: April 2021

Abstract
Purpose: To describe the uptake of 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) in bones and joints for better understanding of the role of 68Ga-FAPI PET in benign and malignant bone lesions and joint diseases. Methods: All 129 68Ga-FAPI PET/MR or PET/CT scans from June 1, 2020 to February 20, 2021 performed at our PET centre were retrospectively reviewed. Foci of elevated 68Ga-FAPI uptake in bones and joints were identified. All lesions were divided into malignant and benign disease. Benign lesions included osteofibrous dysplasia, periodontitis, degenerative bone diseases, arthritis, and other inflammatory or trauma-related abnormalities. The number, locations and SUVmax of all lesions were recorded and analysed. Results: Elevated uptake of 68Ga-FAPI in/around bones and joints were found in 82 cases (63.57%). A total of 295 lesions were identified, including 94 (31.9%) malignant lesions (all were metastases) and 201 (68.1%) benign lesions. The benign lesions consisted of 13 osteofibrous dysplasia, 48 degenerative bone disease, 33 periodontitis, 56 arthritis, and 51 other inflammatory or trauma-related abnormalities. Spine, shoulder joint, alveolar ridge, and pelvis were the most commonly involved locations. Bone metastases were mainly distributed in the spine, pelvis and ribs. Among benign diseases, periodontitis and arthritis are site-specific. The mean SUVmax of bone metastases was significantly higher than that of benign diseases (7.14 ± 4.33 vs. 3.57 ± 1.60, p < 0.0001), but overlap existed. The differences in SUVmax among subgroups of benign diseases were statistically significant (p < 0.0001), with much higher uptake in periodontitis (4.45 ± 1.17). Conclusion: 68Ga-FAPI accumulated in both bone metastases and some benign diseases of bones and joints. Although the uptake of 68Ga-FAPI was often higher in bone metastases, this finding cannot be used to distinguish between benign and malignant lesions.