bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-type calcium channel blocker increases VEGF concentrations in retinal cells and human serum
Authors: Groop Per-Henrik , Kumar Anmol , Mutter Stefan , Parente Erika B. , Harjutsalo Valma , Lithovius Raija , Mathavan Sinnakaruppan , Forsblom Carol , Lehto Markku , Hiltunen Timo P. , Kontula Kimmo K. 
Published: March 2022

Abstract
Objective: Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED). Research design and methods: Müller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 individuals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 individuals from the FinnDiane Study in an oberservational setting. Results: In the cell cultures, medium VEGF concentration increased time-dependently after amlodipine (p<0.01) treatment, but not after losartan (p>0.01), or lisinopril (p>0.01). Amlodipine, but no other AHM, increased serum VEGF concentration (p<0.05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study. Conclusions: LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.
Similarities and differences in systemic risk factors for retinal artery occlusion and retinal vein occlusion: A nationwide case-control study
Authors: Ørskov Marie , Vorum Henrik , Larsen Torben Bjerregaard , Lip Gregory Y. H. , Bek Toke , Skjøth Flemming 
Published: March 2022

Abstract
Background: To investigate the relationship between risk factors of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) and thereby identify similarities and differences between the two types of retinal vascular occlusions.Methods: In this case-control study, 5997 RAO patients were included and matched with three RVO patients each. The RVO patients were matched on sex and age at index date. All patients, personal information, diagnoses, and prescriptions were obtained from the Danish nationwide registries. Adjusted conditional logistic regression was used to investigate the association of RAO and RVO with the included risk factors.Results: RAO was stronger associated with arterial hypertension, heart failure, ischemic heart disease, peripheral artery disease, renal disease, and stroke than RVO, with effect measures ranging from 1.13-2.08. RVO was inversely associated with atrial fibrillation, cataract, and glaucoma with effect measures of 0.84 (95% CI: 0.75-0.95), 0.83 (95% CI: 0.76-0.90) and 0.45 (95% CI: 0.40-0.52), respectively. Conclusion: Differences in the level of associations with the included risk factors suggests differences in the pathophysiologies of the two diseases. The main pathophysiology associated with RAO was atherosclerosis, whereas the main pathophysiology associated with RVO were changes in the pressure gradients of the eyes.
Tripartite motif protein 32 overexpression promotes inflammation and pyroptosis in INS-1 cells via the NF-κB/NLRP3 signaling pathway under high glucose conditions
Authors: wan tingting , Wang Hongjie , Wang Chunxu , Wang Yidan , Li Xiudan , Li Yanbo 
Published: March 2022

Abstract
Background: Type 2 diabetes mellitus (T2DM) is an inflammatory disease, and the primary features are insulin resistance and β-cell dysfunction. Inflammation and pyroptosis contribute to insulin resistance and β-cell dysfunction. Therefore, it is important to identify novel biomarkers to alleviate inflammation and pyroptosis in T2DM. Tripartite motif protein 32 (TRIM32) belongs to the TRIM family and is involved in inflammation, oxidative stress, apoptosis, and autophagy. Moreover, TRIM32 participates in insulin resistance in skeletal muscle and liver; however, its role in β-cell dysfunction remains elusive. Herein, this study investigated the role of TRIM32 in inflammation and pyroptosis in INS-1 cells.Methods and Results: This study confirmed for the first time that serum TRIM32 was upregulated in T2DM patients by ELISA, and high glucose-induced TRIM32 expression in INS-1 cells was validated by western blot, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunofluorescence staining. Overexpression of TRIM32 promoted inflammation and pyroptosis in INS-1 cells under high glucose conditions, whereas silencing TRIM32 had the opposite effects. TUNEL staining and lactate dehydrogenase release assays were performed. In addition, BAY 11-7082 blocked the NF-κB/NLRP3 signaling pathway and significantly attenuated INS-1 cells inflammation and pyroptosis in a high glucose environment. Conclusions: Overexpression of TRIM32 promoted inflammation and pyroptosis in INS-1 cells partly through the NF-κB/NLRP3 signaling pathway under high glucose conditions.
Characterization of Methylation Patterns Associated with Lifestyle Factors and Vitamin D Supplementation in a Healthy Elderly Cohort from Southwest Sweden
Authors: Cruz Maria Araceli Diaz , Ulfenborg Benjamin , Blomstrand Peter , Faresjö Maria , Ståhl Fredrik , Karlsson Sandra 
Published: March 2022

Abstract
Background: Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways.Methods and results: We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the SCL25A24 gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt-pathway and general cancer processes. Conclusions: To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D can be monitored.
Perinatal outcomes of two consecutive strategies for the management of fetal growth restriction: a before-after study
Authors: Demirdjian Sabrina Paola , Meller Cesar Hernan , Berruet Maria Celeste , Dosdoglirian Gonzalo , Etchegaray Adolfo 
Published: March 2022

Abstract
Purpose We aim to compare the perinatal outcomes of two consecutive management strategies for fetal growth restriction (FGR), with or without the inclusion of additional Doppler parameters. Methods A quasi-experimental before/after study was conducted in which we compared a composite perinatal outcome, prematurity rate and neonatal complications between two management strategies in small fetuses. In the strategy 1 (S1), the management was based on fetal biometry and umbilical artery Doppler. The second strategy (S2) added the assessment of uterine and middle cerebral artery Doppler. We also compared outcomes between strategies according to early (≤32 weeks) and late (>32 weeks) diagnosis subgroups. Results We included 396 patients, 163 in S1 and 233 in S2. There were no significant differences in the perinatal composite outcome (p 0.98), prematurity (p 0.19) or in the subgroup analysis. We found a significant reduction in respiratory distress syndrome (RDS) rate with S2 both globally (OR 0.50, p 0.02), and in the early diagnosis subgroup (OR 0.45, p 0.01). In addition, we observed a significant reduction in the incidence of sepsis with S2 both globally (OR 0.30, p 0.04) and in the early diagnosis subgroup (OR 0.25, p 0.02). We did not observe significant differences in necrotizing enterocolitis (p 0.41) and intraventricular hemorrhage (p 1.00). Conclusion The expanded strategy for the management of FGR did not show significant differences in the primary composite outcome or prematurity. However, it was associated with a lower incidence of RDS and neonatal sepsis.
Targeting Cooperation of Chronic Inflammation with Epigenetic Reprogramming Triggers a Synthetic Lethality in Glioblastoma Multiforme
Authors: Lin Kefeng , Gao Wenli , Chen Ning , Wang Han , Wang Ran , Yang Shuyao , Xie Fang , Meng Jiaqi , Lam Eric W.-F. , Ma Chao , Li Suyi , Kang Ning , Hao Yuchao , Wu Zheng , Ge Qi , Guo Lili , Cheng Wei , Chen Puxiang , Wu Hongjin , Yan Jinsong , Jin Di , Jin Bilian 
Published: March 2022

Abstract
Background
Without an effective strategy for targeted therapy, glioblastoma multiforme (GBM) is still incurable, with a median survival of only 15 months. Both chronic inflammation and epigenetic reprogramming are hallmarks of cancer. However, the mechanisms and consequences of their cooperation in GBM remain unknown.
Methods
Western blotting was carried out to detect levels of various histone modifications affected by NF-κB signalling. Then, RNA-seq was used to screen genes encoding methyltransferases and demethylases of histone. Dual-luciferase reporter gene and ChIP assays were performed to determine whether NF-κB activates the transcription of EZH2. Subsequently, ChIP-seq and RT-qPCR were performed to explore the variety of H3K27me3 distribution. Expression levels of p65 and EZH2 in glioma samples were evaluated by IHC, and tumorigenicity assays (in vitro and in vivo) were performed to demonstrate the effects of combining NF-κBi and EZH2i on GBM progression.
Results
We discovered that chronic inflammation governs H3K27me3 reprogramming in GBM through the canonical NF-κB pathway to target EZH2. Being a crucial mediator of chronic inflammation, the canonical NF-κB signalling specifically directs the expression and redistribution of H3K27me3 but not H3K4me3, H3K9me3 and H3K36me3. Then, we identified EZH2 as a key methyltransferase to control inflammation-triggered epigenetic reprogramming in gliomagenesis. Mechanistically, NF-κB selectively drives the expression of EZH2 by activating its transcription, consequently resulting in a global change of H3K27me3 expression and distribution. Furthermore, we find that co-activation of NF-κB and EZH2 confers the poorest clinical outcome, and that the risk for GBM can be accurately molecularly stratified by NF-κB and EZH2. It is notable that NF-κB can potentially cooperate with EZH2 in more than one way, and most importantly, we demonstrated a synthetic lethality of cancer cells induced by combinatory inhibition of NF-κB and EZH2, which both are frequently over-activated in GBM.
Conclusions
We uncover a functional cooperation between chronic inflammation and epigenetic reprogramming in GBM. Thus, combined targeting of NF-κB and EZH2 by inhibitors can be a potent strategy for the effective treatment of this fatal disease.
Green synthesis of Chitosan - Selenium bionanocomposite with high biocompatibility and its marked impact on Las B and RhII genes expression in Pseudomonas aeruginosa
Authors: Selvaraj Karthick Raja Namasivayam , Nizar MohideenNizar , Sudersan AV , Bharani RS , Kumar Ganesh Kumar , Nachiyar Valli 
Published: March 2022

Abstract
Recently, there has been an augmenting demand for chitosan-metal nanocomposites in biomedicine as drug delivery and diagnostic agent due to their notable efficacy and desired biocompatibility. In this present study, chitosan-selenium nanocomposite (CS-SeNC) prepared by in vitro, economical green chemistry principle was evaluated for quorum quenching activity against quorum sensing virulence genes expression in the human pathogenic multidrug-resistant bacterial pathogen Pseudomonas aeruginosa. Biocompatibility of the synthesised CS-SeNC was evaluated on the zebrafish model by determination of expression pattern of oxidative stress enzymes genes –catalase (CAT), superoxide dismutase (SOD1), apoptosis genes p53 and Bax genes in liver tissue. Histopathological analysis of the liver was also conducted. The silencing effect of the synthesised nanocomposite on major virulence factors encoding genes Las B and RhII was investigated by determining relative gene expression rate adopting quantitative real-time reverse transcriptase-polymerase chain reaction. This is followed by studies that measure relative gene expression of respective quorum sensing genes, the effect of CS-SeNC on the quorum sensing genes mediated virulence factors like biofilm formation, pyocyanin production, swarming motility and elastase activity were demonstrated. Relative gene expression of both the genes was significantly reduced in all the dosages of CS-SeNC treatment, with subsequent reduction in the production of all the tested virulence factors of P.aeruginosa. The absence of marked expression of oxidative stress enzymes genes apoptosis genes in the CS-SeNC administrated zebrafish model reveals the best biocompatibility. Liver histology has not shown any marked effect, confirming the best biocompatibility. The present study implies that CS-SeNC prepared by in situ green science principles is the promising antibacterial agent against multiple drug-resistant bacterial strains, which exhibit an antagonistic effect by inhibiting the molecular mechanism of pathogenesis with noteworthy biocompatibility.
Embodiment comfort levels during Motor Imagery training combined with immersive Virtual Reality in spinal cord injury: a case report
Authors: Pais-Vieira Carla , Gaspar Pedro , Matos Demétrio , Alves Leonor Palminha , Cruz Bárbara Moreira da , Azevedo Maria João , Gago Miguel , Poleri Tânia , Perrotta André , Pais-Vieira Miguel 
Published: March 2022

Abstract
Brain-machine interfaces combining visual, auditory, and tactile feedback have been previously used to generate embodiment experiences during spinal cord injury (SCI) rehabilitation. It is not known if adding temperature to these modalities can result in discomfort with embodiment experiences. In this case study, the levels of comfort with the embodiment experiences were investigated in an intervention that required a chronic pain SCI patient to generate lower limb motor imagery commands in an immersive environment combining visual (virtual reality -VR), auditory, tactile, and thermal feedback. Assessments were made pre/post and throughout the intervention (Weeks 0–5), and at seven weeks follow up. Overall, high levels of embodiment in the adapted three-domain scale of embodiment were found throughout the sessions. No significant adverse effects of VR were reported. Sessions induced only a modest reduction in the levels of pain. Overall reductions occurred in all pain scales (Faces, Intensity, Verbal) at follow up. A high degree of comfort in the comfort scale for the thermal-tactile sleeve, in both the thermal and tactile feedback components of the sleeve was reported. This study supports the feasibility of combining multimodal stimulation involving visual (VR), auditory, tactile, and thermal feedback to generate embodiment experiences in neurorehabilitation programs.
Gaps in neonatal thermal care in low-resource settings: A web-based survey of healthcare workers.
Authors: Kyokan Michiko , Jirapaet Veena , Rosa-Mangeret Flavia , Pisoni Giorgia Brambilla , Pfister Riccardo E 
Published: March 2022

Abstract
Background: Hypothermia has been widely regarded as a major contributory factor to neonatal mortality and morbidity in low-resource settings. Despite the recognition of the importance of thermal care for neonates a century ago and the established WHO guidelines, a high prevalence of neonatal hypothermia is still regularly reported. Hypothermia is avoidable in the majority of neonates because it is not a complication of prematurity but more the result of inadequate thermal care. The objective of this study was to explore the current gaps in knowledge and practice in neonatal thermal care among healthcare workers in low-resource settings.Methods: We conducted a 2-round, web-based survey of a purposive and snowball sample of healthcare workers in neonatal care in low-resource settings. The questionnaire was developed using themes of neonatal thermal care extracted from existing neonatal care guidelines, including WHO’s. The survey asked multiple-choice questions, supplemented by open-ended questions to capture first hand insights and information on neonatal thermal care. Results of the survey were analysed using Microsoft Excel. Data was collated and summarized using descriptive measures. Results: Almost all participants acknowledged the importance of all the WHO warm chain elements, however, fewer participants responded positively regarding the practice of this warm chain. Only 56% of the participants acknowledged the usefulness of checking the hand or foot temperature by hand-touch. The usefulness of the axillary or rectal temperature was valued higher than that of the hand or foot temperature as an indicator of cold stress. Opinions diverged regarding the hand or foot temperature, including apparent inaccuracy compared to axillary or rectal temperature. Preferences on rewarming strategies widely differed among participants and so did the availability of warming equipment in their institutions. Conclusions: We identified the general acknowledgment of the importance of the WHO warm chain but also its limited practice. We also identified that an inadequate understanding of cold stress underestimates the potential benefits of the hand or foot temperature and leads to missed opportunities for timely prevention of hypothermia. Furthermore, lack of consistent guidance on equipment for rewarming hypothermic neonates hampers recovery.
Changes in Hemostasis during Liver Transplantation in Children
Authors: Novikov D. I. , Zaitsev A. Yu. , Dubrovin K. V. , Bespalov E. K. , Filin A. V. 
Published: February 2022

The objective: to assess changes of clinical and laboratory hemostasic parameters in children at the stages of orthotopic liver transplantation.Subjects and Methods. A single-centre, prospective, pilot study of coagulation test scores was performed in 20 children aged 0 to 11 years with hepatoblastoma after a course of PRETEX IV chemotherapy who underwent liver transplantation from a related donor.Results. Children from 0 to 11 years old with hepatoblastoma, after chemotherapy, retain the normal functional activity of the hemostasis system at the pre-hepatic stage of transplantation: APTT 34.6 (34.45; 38.65) s; prothrombin index (PI) 83.53 (74.09; 87.87) %; INR 1.22 (1.16; 1.42) in the 0‒2 year group, APTT 40.45 (34.9; 41, 68), PI 75.57 (64.41; 80.45) %, and INR 1.39 (1.36; 1.87) in the group aged 3‒11 years. Severe hypocoagulation develops by the end of the hepatic stage and in the first 15 minutes after the start of arterial blood flow through the graft: CT and CFT from 195.0 (189.0; 228.5) s and 163.0 (129.5; 171.5) s to 537.0 (456.0; 1,651.5) s and 468.0 (324.5; 611.5) s (p < 0.05), respectively, in the INTEM test. Hypocoagulation at this time develops due to deficiency of coagulation factors and the release of endogenous glycosaminoglycans from the endothelium transplant, as indicated by an increase in CT and CFT to 666.0 (468.5; 2,209.5) s and 254.5 (203.25; 305.75) s in INTEM, CT to 525.0 (389.0; 2028.0) s with p < 0.05 in HEPTEM in children under the age group of up to 2. Within 1 hour after the start of arterial blood flow, the effects of systemic heparinoid effects persist, which is confirmed by the dynamics of CT 360.0 (219.5; 2,116.5) s with up to 960.0 (560.5; 1,440.5) s with p < 0.05 in the EXTEM test.Conclusion. Changes in hemostasis system parameters during surgery make it possible to judge about rapidly developing coagulation and anticoagulation disorders in children of the presented age groups. Specific changes in the coagulation profile at the stages of liver transplantation in children under the age of 11 inclusive, make it possible to do without routine correction of changes in the hemostasis system.
Features of functioning of the EAEU аs an integration association
Authors: Бударина Н.А. , Прокопович Р.С. 
Published: March 2022

В данной статье рассмотрены основные аспекты деятельности Евразийского экономического союза как интеграционного объединения. Основное внимание уделено анализу экономических показателей Евразийского экономического союза в сравнении с ведущим интеграционным объединением мира - Европейским Союзом. Отражены характерные черты ЕАЭС и особенности его развития. Выявлены ключевые причины различных темпов развития и становления ЕАЭС и ЕС в контексте рассматриваемых экономических показателей
This article examines the main aspects of the Eurasian Economic Union as an integration association. The main attention is paid to the analysis of the economic indicators of the EAEU in comparison with the leading integration association in the world - the EU. The characteristic features of the EAEU and the features of its development are reflected. The key reasons for the different rates of development and formation of the EAEU and the EU are identified in the context of the economic indicators under consideration.
Afghanistan still attracts
Authors: Карпович О.Г. , Мустафабейли А.М. 
Published: March 2022

В мировой внешнеполитической практике произошло беспрецедентное событие: великая держава - США - в итоге двадцатилетней войны с группировкой, признанной ООН террористической - «Движение талибов» (ДТ), - заключает с ней мирное соглашение, предполагающее ее участие во власти, в том числе в качестве ведущей политической силы. В соглашении удовлетворяется ключевое требование ДТ об установлении конкретных сроков вывода из страны американских войск. Взамен талибы соглашаются принять меры по недопущению создания угроз безопасности США и их союзников на территории Афганистана со стороны членов Движения, а также «Аль-Каиды», «Исламского государства» (ИГ), запрещенных в России, других террористических группировок и отдельных лиц, а также вступить в переговорный процесс в целях изыскания путей достижения межафганского примирения и формирования инклюзивных институтов государственной власти.
An unprecedented event has occurred in world foreign policy practice: a great power - the United States - as a result of a twenty - year war with a group recognized by the UN as a terrorist group - the Taliban Movement (DT) - concludes a peace agreement with it, assuming its participation in power, including as a leading political force. The agreement satisfies the key requirement of the DT to establish specific deadlines for the withdrawal of American troops from the country. In return, the Taliban agree to take measures to prevent the creation of threats to the security of the United States and its allies in Afghanistan by members of the Movement, as well as Al-Qaeda, Islamic State (IS), banned in Russia, other terrorist groups and individuals, as well as to enter into a negotiation process in order to find ways to achieve inter-Afghan reconciliation and the formation of inclusive institutions of state power.