bluuebunny/crossref_metadata_2025_split huggingface dataset:
Нормативно-правові аспекти механізму забезпечення національної безпеки у воєнній сфері в кризових ситуаціях
Authors: Каптан М. , Руснак Ю. , Гудима О. , Коміссарова Н. , Бейкун А. 
Published: July 2023

Сучасний рух суспільних процесів в Україні та світі зумовлює необхідність формування ефективного механізму управління національною безпекою, спроможного забезпечити поступ суспільства та держави на шляху до спільноти розвинутих демократичних країн. Цей механізм має забезпечити захист життєво важливих національних інтересів у складному зовнішньому та внутрішньому середовищі, яке характеризується низкою викликів і загроз національній безпеці, в тому числі у воєнній сфері.Очевидним є актуальність здійснення перегляду ефективності й аналіз механізму забезпечення національної безпеки у воєнній сфері, насамперед щодо визначення функціонування системи управління національною безпекою у кризових умовах, з метою їїудосконалення.
Метою статті є аналіз механізмів забезпечення національної безпеки в умовах кризових і надзвичайних ситуацій, в умовах надзвичайного стану та особливого періоду, що базуються на основі нормативно-правових актів міжнародного та національного рівня.
У статті опрацьовано варіант механізму забезпечення національної безпеки у воєнній сфері для кризових ситуацій шляхомзвернення України до країн-гарантів.Означене звернення базується на Меморандумі, та рекомендаціях щодо практичного впровадженнямеханізму забезпечення національної безпеки. Зазначений механізм буде сприяти підвищенню ефективності державної політики та державного управління в сфері забезпечення національної безпеки, насамперед, для умов кризових ситуацій у воєнній сфері, максимально враховувати положення Меморандуму й особливості України, як країни, що добровільно відмовилася від ядерної зброї.
У випадку виявлення загроз незалежності, суверенітету, недоторканості кордонів України, здійснення економічного примушення, безпосереднього конфлікту або агресії проти України, керівництвом держави приймається рішення щодо комплексного застосування зовнішньополітичних механізмів врегулювання кризових ситуацій, що визначені відповідними міжнародними документами.
ЗАБЕЗПЕЧЕННЯ ЯКОСТІ ВИЩОЇ ВІЙСЬКОВОЇ ОСВІТИ ТА ПРОБЛЕМИ РОЗВИТКУ ПРОФЕСІЙНОЇ ВІЙСЬКОВОЇ ОСВІТИ В УКРАЇНІ
Authors: Рахманов Віталій 
Published: July 2023

У статті розглянуто забезпечення якості вищої освіти та проблеми розвитку професійної військової освіти в Україні. Системним підґрунтям для розбудови системи якості вищої освіти на інституційному, національному та європейському рівнях слугують стандарти і рекомендації щодо забезпечення якості в Європейському просторі вищої освіти. Якість вищої освіти базується на системній основі, що передбачає наявність зрозумілих і взаємоузгоджених законодавчих норм, інституційних форм, організаційних механізмів і процедур, спрямованих на вибудовування та реалізацію відкритих і довірливих стосунків між державою та закладами вищої військової освіти для реалізації їх спільної відповідальності за надання якісної освіти та її розвиток відповідно до вимог суспільства.
Реформування системи військової освіти свідчить, що необхідно розвивати військову освіту в Україні у межах основних тенденцій, притаманних провідним державам країнам-членам НАТО. До одного з основних елементів системи військової освіти належить професійна військова освіта, розвиток якої в Україні має відбуватись з урахуванням стандартів та принципів, що застосовуються у провідних країнах, які на практиці реалізують ідею зовнішнього та внутрішнього оцінювання як перевірку відповідності закладів певним стандартам, що активно впроваджується у практику інституційного оцінювання та акредитації практично в усіх національних системах. В основі цих стандартів належить поняттю якості освіти, а саме формування системи внутрішнього та зовнішнього забезпечення якості у закладах вищої військової освіти, ефективне функціонування яких вважається гарантією належного рівня формування компетентностей об’єктами навчання.
Glucose metabolism and its role in the maturation and migration of human CD1c+ dendritic cells following exposure to BCG
Authors: Triglia Denise , Gogan Karl M. , Keane Joseph , O’Sullivan Mary P. 
Published: July 2023

IntroductionTuberculosis (TB) still kills over 1 million people annually. The only approved vaccine, BCG, prevents disseminated disease in children but shows low efficacy at preventing pulmonary TB. Myeloid dendritic cells (mDCs) are promising targets for vaccines and immunotherapies to combat infectious diseases due to their essential role in linking innate and adaptive immune responses. DCs undergo metabolic reprogramming following exposure to TLR agonists, which is thought to be a prerequisite for a successful host response to infection. We hypothesized that metabolic rewiring also plays a vital role in the maturation and migration of DCs stimulated with BCG. Consequently, we investigated the role of glycolysis in the activation of primary human myeloid CD1c+ DCs in response to BCG. Methods/resultsWe show that CD1c+ mDC mature and acquire a more energetic phenotype upon challenge with BCG. Pharmacological inhibition of glycolysis with 2-deoxy-D-glucose (2-DG) decreased cytokine secretion and altered cell surface expression of both CD40 and CCR7 on BCG-challenged, compared to untreated, mDCs. Furthermore, inhibition of glycolysis had differential effects on infected and uninfected bystander mDCs in BCG-challenged cultures. For example, CCR7 expression was increased by 2-DG treatment following challenge with BCG and this increase in expression was seen only in BCG-infected mDCs. Moreover, although 2-DG treatment inhibited CCR7-mediated migration of bystander CD1C+ DCs in a transwell assay, migration of BCG-infected cells proceeded independently of glycolysis. DiscussionOur results provide the first evidence that glycolysis plays divergent roles in the maturation and migration of human CD1c+ mDC exposed to BCG, segregating with infection status. Further investigation of cellular metabolism in DC subsets will be required to determine whether glycolysis can be targeted to elicit better protective immunity against Mtb.
Insight into contact force local impedance technology for predicting effective pulmonary vein isolation
Authors: Lepillier Antoine , Maggio Ruggero , De Sanctis Valerio , Malacrida Maurizio , Stabile Giuseppe , Zakine Cyril , Champ-Rigot Laure , Anselmino Matteo , Segreti Luca , Dell’Era Gabriele , Garnier Fabien , Mascia Giuseppe , Pandozi Claudio , Dello Russo Antonio , Scaglione Marco , Cosaro Giuseppe , Ferraro Anna , Paziaud Olivier , Maglia Giampiero , Solimene Francesco 
Published: July 2023

BackgroundHighly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created.ObjectiveWe aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry.MethodsA total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included.ResultsIn all, 13,891 radiofrequency (RF) applications of ≥3 s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19 Ω vs. 153.0 ± 13 Ω, p &lt; 0.0001 for baseline LI; 22.1 ± 9 Ω vs. 14.4 ± 5 Ω, p &lt; 0.0001 for LI drop). On the basis of Receiver operating characteristic curve analysis, the ideal LI drop, which predicted successful ablation, was &gt;21 Ω at anterior sites and &gt;18 Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13–0.16, p &lt; 0.0001) whereas both CF and LI drop were inversely related with delivery time (DT) (−0.22, −0.23 to −0.20, p &lt; 0.0001 for CF; −0.27, −0.29 to −0.26, p &lt; 0.0001 for LI drop).ConclusionAn LI drop &gt;21 Ω at anterior sites and &gt;18 Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT.Clinical trial registrationhttp://clinicaltrials.gov/, identifier: NCT03793998.
Exercise improved bone health in aging mice: a role of SIRT1 in regulating autophagy and osteogenic differentiation of BMSCs
Authors: Zhu Chengyu , Ding Haili , Shi Liang , Zhang Shihua , Tong Xiaoyang , Huang Mei , Liu Lifei , Guan Xiaotian , Zou Jun , Yuan Yu , Chen Xi 
Published: July 2023

IntroductionThis study was designed to investigate the effect of running exercise on improving bone health in aging mice and explore the role of the SIRT1 in regulating autophagy and osteogenic differentiation of Bone marrow Mesenchymal Stem Cells (BMSCs).MethodsTwelve-month-old male C57BL/6J mice were used in this study as the aging model and were assigned to treadmill running exercise for eight weeks. Non-exercise male C57BL/6J mice of the same old were used as aging control and five-month-old mice were used as young controls. BMSCs were isolated from mice and subjected to mechanical stretching stimulation in vitro.ResultsThe results showed that aging mice had lower bone mass, bone mineral density (BMD), and autophagy than young mice, while running exercise improved BMD and bone mass as well as upregulated autophagy in bone cells. Mechanical loading increased osteogenic differentiation and autophagy in BMSCs, and knockdown of SIRT1 in BMSCs demonstrated that SIRT1-regulated autophagy involved the mechanical loading activation of osteogenic differentiation.ConclusionTaken together, this study revealed that exercise improved bone health during aging by activating bone formation, which can be attributed to osteogenic differentiation of BMSCs through the activation of SIRT1-mediated autophagy. The mechanisms underlying this effect may involve mechanical loading.
Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer
Authors: Huang Maosen , Wu Yancen , Cheng Linyao , Fu Lihua , Yan Haochao , Ru Haiming , Mo Xianwei , Yan Linhai , Su Zijie 
Published: July 2023

BackgroundGlucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis.MethodsPET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis.ResultsThe glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer.ConclusionsGMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets.
Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease
Authors: Caillard Pauline , Vigneau Cécile , Halimi Jean-Michel , Hazzan Marc , Thervet Eric , Heitz Morgane , Juillard Laurent , Audard Vincent , Rabant Marion , Hertig Alexandre , Subra Jean-François , Vuiblet Vincent , Guerrot Dominique , Tamain Mathilde , Essig Marie , Lobbedez Thierry , Quemeneur Thomas , Legendre Mathieu , Ganea Alexandre , Peraldi Marie-Noëlle , Vrtovsnik François , Daroux Maïté , Makdassi Raïfah , Choukroun Gabriel , Titeca-Beauport Dimitri 
Published: July 2023

Background and objectivesActivation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease.MethodsWe conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3&lt;1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival.ResultsOf the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26–64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298–977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr).ConclusionIn patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.
CD4+ T-cell-dependent differentiation of CD23+ follicular B cells contributes to the pulmonary pathology in a primary Sjögren’s syndrome mouse model
Authors: Sato-Fukuba Mami , Arakaki Rieko , Ushio Aya , Otsuka Kunihiro , Nagao Ruka , Matsuzawa Shigefumi , Tawara Hiroaki , Tsunematsu Takaaki , Ishimaru Naozumi 
Published: July 2023

IntroductionPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS.ResultsThe histopathological analysis of lung tissues obtained from NFS/sld mice that have undergone neonatal thymectomy was performed. Moreover, in vivo and in vitro experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23+ follicular B (FB) cells. In vitro and pulmonary B cells were more readily driven to CD23+ FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23+ FB cell differentiation was found to be enhanced in a CD4+ T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice.DiscussionA Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells.
A modified perioperative regimen for deceased donor kidney transplantation in presensitized recipients without prior desensitization therapy
Authors: Guo Zhiliang , Zhao Daqiang , Sa Rula , Wang Lu , Li Songxia , Zhao Guangyuan , Zhu Lan , Chen Gang 
Published: July 2023

BackgroundRenal transplantation in HLA-presensitized recipients entails an increased risk of antibody-mediated rejection (AMR) and graft loss. There is currently no accepted standard treatment protocol that can help transplant surgeons safely perform deceased donor (DD) kidney transplantation in presensitized patients without pretransplant desensitization.MethodsFifty-one panel-reactive antibody (PRA)-positive recipients and 62 PRA-negative retransplant recipients (control) who received DD renal transplantation were included. Patients in the presensitized group (donor-specific antibody [DSA]-positive, n=25; DSA-negative, n=26) without desensitization received a modified perioperative treatment starting on day 0 or -1 with rituximab, thymoglobulin, and low daily doses of intravenous immunoglobulin (IVIG, 10-20 g/d, for 14 days). Plasmapheresis was performed once before surgery in DSA-positive recipients.ResultsThe median follow-up time was 51 months in the presensitized group and 41 months in the control group. The incidence of early acute rejection (AR) and AMR (including mixed rejection) was 35.3% and 13.7% in the presensitized group, respectively, significantly higher than in the control group (14.5% and 1.6%, respectively). Within the presensitized group, the DSA-positive subgroup had more AMR than the DSA-negative subgroup (24.0% vs. 3.8%), but the incidence of T cell-mediated rejection was comparable (20.0% vs. 23.4%). In the presensitized group, all rejections were successfully reversed, and graft function remained stable during follow-up. The 1-year and 3-year survival rates of the grafts and recipients in this group were 98.0%.ConclusionWith a modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who received DD kidney transplantation without prior desensitization.
The association between dementia and the risk of hypoglycaemia events among patients with diabetes mellitus: a propensity-score matched cohort analysis
Authors: Alsharif Alaa A. , Wong Ian C. K. , Ma Tian , Lau Wallis , Alhamed Meshari , Alwafi Hassan , Wei Li 
Published: July 2023

BackgroundHypoglycaemia commonly occurs in patients diagnosed with diabetes mellitus (DM) and dementia. The impact of dementia on hypoglycaemic events is controversial. Thus, we evaluated whether dementia increases the risk of hypoglycaemic events in older patients diagnosed with DM.DesignA retrospective cohort study.SettingWe used the IQVIA Medical Research Data (IMRD-UK) database (formerly known as the THIN database).ParticipantsAll patients aged ≥55 years and diagnosed with DM who were prescribed at least two prescriptions of antidiabetic medication between 2000 and 2017. Two groups of patients, dementia and non-dementia group, were propensity-score (PS) matched at 1:2. The risk of hypoglycaemia was assessed through a Cox regression analysis.Main outcome and measuresHypoglycaemic events were determined during the follow-up period by Read codes.ResultsFrom the database, 133,664 diabetic patients were identified, with a mean follow-up of 6.11 years. During the study period, 7,762 diabetic patients diagnosed with dementia were matched with 12,944 diabetic patients who had not been diagnosed with dementia. The PS-matched Cox regression analysis showed that patients diagnosed with dementia were at a 2-fold increased risk for hypoglycaemic events compared with those not diagnosed with dementia (hazard ratio [HR], 2.00; 95% CI, 1.63–2.66). A similar result was shown for a multivariable analysis using all patient data (adjusted HR, 2.25; 95% CI, 2.22–2.32).ConclusionOur findings suggest that diabetic patients with a diagnosis of dementia have a statistically significant higher risk of experiencing hypoglycaemia.
Glycosaminoglycans and fucoidan have a protective effect on experimental glomerulonephritis
Authors: Buijsers Baranca , Maciej-Hulme Marissa , Jacobs Maaike , Bebber Marinka Bakker-van , de Graaf Mark , Salmenov Rustem , Parr Naomi , Rabelink Ton J. , Nijenhuis Tom , van der Vlag Johan 
Published: July 2023

Background: The glomerular endothelial glycocalyx is degraded during inflammation. The glycocalyx plays a pivotal role in endothelial function and is involved in many processes including binding of chemokines and cytokines, leukocyte trafficking, and preventing proteinuria. HS-based therapeutics are a promising novel class of anti-inflammatory drugs to restore a compromised endothelial glycocalyx under inflammatory conditions. Recently, we demonstrated that treatment with HS extracted from unstimulated glomerular endothelial glycocalyx (unstimulated HSglx) reduced albuminuria during anti-GBM induced glomerulonephritis. Since endothelial HS domains are distinct in unstimulated versus inflammatory conditions, we hypothesized that 1) unstimulated HSglx, 2) LPS-stimulated HSglx, 3) the HS-mimetic fucoidan and 4) the glycosaminoglycan preparation sulodexide, which is a mixture of low molecular weight heparin and dermatan sulfate, might have different beneficial effects in experimental glomerulonephritis.Methods: The effect of unstimulated HSglx, LPS HSglx, Laminaria japonica fucoidan, or sulodexide on experimental glomerulonephritis was tested in LPS-induced glomerulonephritis in mice. Analyses included urinary albumin creatinine measurement, cytokine expression in plasma and renal cortex, and renal influx of immune cells determined by flow cytometry and immunofluorescence staining. Furthermore, the observed in vivo effects were evaluated in cultured glomerular endothelial cells and peripheral blood mononuclear cells by measuring cytokine and ICAM-1 expression levels. The ability of the compounds to inhibit heparanase activity was assessed in a heparanase activity assay.Results: Treatment of mice with LPS HSglx or sulodexide near-significantly attenuated LPS-induced proteinuria. All treatments reduced plasma MCP-1 levels, whereas only fucoidan reduced IL-6 and IL-10 plasma levels. Moreover, all treatments reversed cortical ICAM-1 mRNA expression and both fucoidan and sulodexide reversed cortical IL-6 and nephrin mRNA expression. Sulodexide decreased renal influx of CD45+ immune cells whereas renal influx of macrophages and granulocytes remained unaltered for all treatments. Although all compounds inhibited HPSE activity, fucoidan and sulodexide were the most potent inhibitors. Notably, fucoidan and sulodexide decreased LPS-induced mRNA expression of ICAM-1 and IL-6 by cultured glomerular endothelial cells.Conclusion: Our data show a potentially protective effect of glycosaminoglycans and fucoidan in experimental glomerulonephritis. Future research should be aimed at the further identification of defined HS structures that have therapeutic potential in the treatment of glomerular diseases.