356 results on '"Petkovic A"'
Search Results
2. Development of Novel ROCK Inhibitors via 3D-QSAR and Molecular Docking Studies: A Framework for Multi-Target Drug Design.
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Beljkas, Milan, Petkovic, Milos, Vuletic, Ana, Djuric, Ana, Santibanez, Juan Francisco, Srdic-Rajic, Tatjana, Nikolic, Katarina, and Oljacic, Slavica
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RHO-associated kinases , *COMPUTER-assisted drug design , *DRUG design , *CYTOSKELETON , *MOLECULAR docking - Abstract
Background/Objectives: Alterations in the actin cytoskeleton correlates to tumor progression and affect critical cellular processes such as adhesion, migration and invasion. Rho-associated coiled-coil-containing protein kinases (ROCK1 and ROCK2), important regulators of the actin cytoskeleton, are frequently overexpressed in various malignancies. The aim of this study was therefore to identify the key structural features of ROCK1/ROCK2 inhibitors using computer-aided drug design (CADD) approaches. In addition, new developed ROCK inhibitors provided a significant framework for the development of multitarget therapeutics—ROCK/HDAC (histone deacetylases) multitarget inhibitors. Methods: 3D-QSAR (Quantitative structure-activity relationship study) and molecular docking study were employed in order to identify key structural features that positively correlate with ROCK inhibition. MDA-MB-231, HCC1937, Panc-1 and Mia PaCa-2 cells were used for evaluation of anticancer properties of synthesized compounds. Results: C-19 showed potent anti-cancer properties, especially enhancement of apoptosis and cell cycle modulation in pancreatic cancer cell lines. In addition, C-19 and C-22 showed potent anti-migratory and anti-invasive effects comparable to the well-known ROCK inhibitor fasudil. Conclusions: In light of the results of this study, we propose a novel multi-target approach focusing on developing dual HDAC/ROCK inhibitors based on the structure of both C-19 and C-22, exploiting the synergistic potential of these two signaling pathways to improve therapeutic efficacy in metastatic tumors. Our results emphasize the potential of multi-target ROCK inhibitors as a basis for future cancer therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Biomarkers and Diagnostic Thresholds for Congenital Hyperinsulinism.
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Petkovic, Grace, Park, Julie, Collingwood, Catherine, Senniappan, Senthil, and Didi, Mohammed
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FREE fatty acids , *CHILDREN'S hospitals , *HYPERINSULINISM , *MEDICAL screening , *DIAGNOSIS methods - Abstract
ABSTRACT Context Objective Design Patients Results Conclusions Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C‐peptide in the context of hypoglycemia.We aimed to better clarify a diagnostic threshold value of C‐peptide for children presenting with CHI.This was a retrospective case‐control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C‐peptide, insulin, free fatty acid (FFA) and B‐hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions.All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed.Median [C‐peptide] were statistically significantly different between CHI (147) and non‐CHI (72) patients,
p < 0.05. The Youden Index indicated that a [C‐peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non‐CHI patients (p < 0.01). Median [BOHB] was 0 μmol/L in CHI patients as compared with 2378 μmol/L for non‐CHI patients (p < 0.01). Median [FFA] levels were 1910 μmol/L in the non‐CHI cohort, compared with 0 in the CHI cohort (p < 0.01).This study suggests that a C‐peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C‐peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. The Continuing Decline of Languages and Literature.
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PETKOVIC, JANE and BURNS, RAYMOND
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LANGUAGE & languages , *EDUCATION & politics , *CLASSICAL languages , *LATIN language - Abstract
The article reports on the decline of Latin as a high school subject and its implications for education in New South Wales. Topics include the erosion of academic rigor in modern curricula, the political influence on education systems, and the challenges of maintaining proficiency in classical languages like Latin in the contemporary educational landscape.
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- 2024
5. Spontaneous Emergence of Robustness to Light Variation in CNNs With a Precortically Inspired Module.
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Petkovic, J. and Fioresi, R.
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IMAGE recognition (Computer vision) , *CONVOLUTIONAL neural networks , *VISUAL cortex , *LIGHT intensity , *MATHEMATICAL models - Abstract
The analogies between the mammalian primary visual cortex and the structure of CNNs used for image classification tasks suggest that the introduction of an additional preliminary convolutional module inspired by the mathematical modeling of the precortical neuronal circuits can improve robustness with respect to global light intensity and contrast variations in the input images. We validate this hypothesis using the popular databases MNIST, FashionMNIST, and SVHN for these variations once an extra module is added. [ABSTRACT FROM AUTHOR]
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- 2024
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6. A data-driven approach to resilience in air traffic management: case study Barcelona area control centre.
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Mirkovic, Bojana, Timotic Petkovic, Doroteja, Netjasov, Fedja, Crnogorac, Dusan, Verdonk Gallego, Christian Eduardo, Xia, Chen, and Malakis, Stathis
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AIR traffic , *AIR traffic controllers , *AERONAUTICAL navigation , *SUPPLY & demand , *SOCIOTECHNICAL systems - Abstract
Traditional approaches to safety assessment and management are limited when it comes to complex socio-technical systems, such as air traffic management (ATM). A modelling approach proposed in this paper relies on Resilience Engineering perspective, which is about work-as-done, where safety is one of the targets trading off with other goals. The model provides a description of everyday practices, procedures, strategies, etc. in providing, not only safe, but also efficient ATM system operations. The aim of the model is to help air navigation service providers (ANSPs) that still do not measure and monitor resilience to distinguish between main drivers of traditional safety and drivers of resilience emerging from everyday adaptation to uncertainties. The conceptual layer of the model uses the analogy of lever mechanism to represent the balancing between the demand side (including the uncertainties) and available resources on the supply side that considers air traffic controllers (ATCos), tools and working procedures. The quantitative layer of the model allows identification of periods of resilient behavior (negative demand-capacity imbalances) and thereby steers ANSPs in discovering sources of resilience and finding appropriate resilience indicators to monitor in the future. A data-driven application of the proposed model is shown with the example of Barcelona Area Control Centre – assessment of balancing conditions, analysis of proposed resilience indicators and discussion of the trade-offs. This research focuses on the tactical imbalances that emerge from work-as-done on an everyday basis. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Analysis of events from sudden isolated dysarthria to diagnosis of myasthenic crisis: myasthenia gravis mimicking acute lacunar stroke—a case report.
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Miletic, Simona Petkovic and Ahmed, Sheikh Ruksana Binte
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DYSARTHRIA , *LACUNAR stroke , *MYASTHENIA gravis , *OLDER people , *DIAGNOSIS , *CRISIS management , *OLDER patients - Abstract
Background: Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), necessitating ventilation. Achieving a safe and timely diagnosis of myasthenic crisis with atypical, isolated presentation is a considerable challenge particularly in elderly patients, where myasthenia gravis can present with isolated dysarthria in rare instances, giving a clinical impression of lacunar stroke. Case presentation: We present a compelling case of a 73-year-old Caucasian female presenting with abrupt onset of isolated dysarthria. Despite initial treatment for a presumed lacunar stroke, subsequent evaluations led to her diagnosis of a myasthenic crisis. Within 72 h of admission, the patient developed dysphagia and shortness of breath, requiring supplemental oxygen. The case highlights the sequential progression of events from the atypical presentation of isolated dysarthria and its course to the management of a myasthenic crisis. Conclusion: Our reported case focuses on the discussion of myasthenia that mimicked a lacunar stroke and was finally diagnosed at a critical time of medical crisis. This case highlights the imperative notion that isolated dysarthria in elderly individuals warrants vigilant monitoring for possible myasthenia gravis, given the low incidence of lacunar stroke presenting with only dysarthria. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Imaging in Infective Endocarditis—Current Opinions and Trends in Cardiac Computed Tomography.
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Petkovic, Ana, Menkovic, Nemanja, Petrovic, Olga, Bilbija, Ilija, Nisevic, Miodrag, Radovanovic, Nikola N., Stanisavljevic, Dejana, Putnik, Svetozar, Maksimovic, Ruzica, and Ivanovic, Branislava
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TRANSESOPHAGEAL echocardiography , *COMPUTED tomography , *CORONARY artery disease , *INFECTIVE endocarditis , *DIAGNOSIS methods , *ECHOCARDIOGRAPHY - Abstract
Infective endocarditis is a rare disease with an increasing incidence and an unaltered high mortality rate, despite medical development. Imaging plays an integrative part in the diagnosis of infective endocarditis, with echocardiography as the initial diagnostic test. Research data in the utility of cardiac computed tomography (CCT) in the diagnostic algorithm of IE are rising, which indicates its importance in detection of IE-related lesion along with the exclusion of coronary artery disease. The latest 2023 European Society of Cardiology Guidelines in the management of IE classified CCT as class of recommendation I and level of evidence B in detection of both valvular and paravalvular lesions in native and prosthetic valve endocarditis. This review article provides a comprehensive and contemporary review of the role of CCT in the diagnosis of IE, the optimization of acquisition protocols, the morphology characteristics of IE-related lesions, the published data of the diagnostic performance of CCT in comparison to echocardiography as the state-of-art method, as well as the limitations and future possibilities. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Evaluation of Nasal Decongestants by Literature Review.
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Petkovic, Stasa, Maletic, Ivana, Djuric, Sonja, Dragutinovic, Ninoslava, and Milovanovic, Olivera
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NASAL vasoconstrictors , *EPHEDRINE , *OXYMETAZOLINE , *EDEMA , *DOSAGE forms of drugs - Abstract
Over-the-counter drugs are medicines that are available to consumers without a prescription. The most common оver - the-counter preparations in self - medication are nasal decongestants that can be used systemically or locally in the form of drops or nasal sprays. The most common indications for nasal decongestants are viral infections and allergic conditions in order to alleviate the symptoms so it is necessary to inform the users about the type of drug, the active substance it contains and the correct dosage regimen. Given their availability and the prevailing safety precaution, these preparations can lead to numerous prolonged conditions and complications. The mechanism of action of nasal decongestants is based on the reduction of blood vessels' swelling in the nose, which helps the opening of the airway. As a result, most nasal decongestants cause vasoconstriction (narrowing of blood vessels). There are nasal decongestants that block histamine and have a good effect on people who suffer from seasonal allergies. Availability (free sale) and prolonged use of the decongestant lead to a decrease in the sensitivity of the alpha receptor, which leads to the need to increase the dose at shorter time intervals to achieve the same effect. As a consequence, patients use excessive, uncontrolled doses of nasal decongestants, which is a public problem and warns of the necessity of identification and the taking of measures to prevent their uncontrolled procurement and use. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Synthesis of Piperazin-2-one Derivatives via Cascade Double Nucleophilic Substitution.
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Petkovic, Milos, Kusljevic, Dušica, Jovanovic, Milos, Jovanovic, Predrag, Tasic, Gordana, Simic, Milena, and Savic, Vladimir
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BIOACTIVE compounds , *ALKYL chlorides , *CONJUGATED systems , *NORMAL-phase chromatography , *BUTYRATES - Abstract
This article discusses the synthesis and characterization of several compounds, including piperazinone derivatives. The compounds are described in terms of their chemical structures, physical properties, and spectroscopic data. The authors provide detailed information about the synthesis procedure, yield, and characterization techniques used. This information can be useful for researchers studying these specific compounds or related topics. The authors acknowledge the University of Belgrade, Faculty of Pharmacy for their support, and additional supporting information is available online. [Extracted from the article]
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- 2024
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11. The effects of sex on extinction dynamics of Chlamydomonas reinhardtii depend on the rate of environmental change.
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Petkovic, Nikola and Colegrave, Nick
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CHLAMYDOMONAS reinhardtii , *ENVIRONMENTAL degradation , *CHLAMYDOMONAS , *BIOLOGICAL extinction , *REPRODUCTION , *SURVIVAL rate - Abstract
The continued existence of sex, despite many the costs it entails, still lacks an adequate explanation, as previous studies demonstrated that the effects of sex are environment‐dependent: sex enhances the rate of adaptation in changing environments, but the benefits level off in benign conditions. To the best of our knowledge, the potential impact of different patterns of environmental change on the magnitude of these benefits received less attention in theoretical studies. In this paper, we begin to explore this issue by examining the effect of the rate of environmental deterioration (negatively correlated with population survival rate), on the benefits of sex. To investigate the interplay of sex and the rate of environmental deterioration, we carried out a long‐term selection experiment with a unicellular alga (Chlamydomonas reinhardtii), by manipulating mode of reproduction (asexual, facultative or obligate sexual) and the rate of environmental deterioration (an increase of salt concentration). We monitored both the population size and extinction dynamics. The results revealed that the relative advantage of sex increased at the intermediate rate and plateaued at the highest rate of environmental deterioration. Obligate sexual populations had the slowest extinction rate under the intermediate rate of environmental deterioration, while facultative sexuality was favoured under the high rate‐treatment. To the best of our knowledge, our study is the first to demonstrate that the interplay of sex and the rate of environmental deterioration affects the probability of survival, which indicates that mode of reproduction may be an important determinant of survival of the anthropogenic‐induced environmental change. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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12. Precipitation Vertical Structure Characterization: A Feature-Based Approach.
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Arulraj, Malarvizhi, Petkovic, Veljko, Ferraro, Ralph R., and Meng, Huan
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K-means clustering , *ATMOSPHERIC models , *STORMS , *MICROPHYSICS , *RADAR , *RADAR meteorology - Abstract
The three-dimensional (3D) structure of precipitation systems is highly dependent on hydrometeor formation processes and microphysics. This study aims to characterize distinct vertical profiles of precipitation regimes by relying on the availability of a high-quality, spatially dense radar network and its capability to observe the 3D structure of the storms. A deep-learning-based framework, coupled with unsupervised clustering methods, is developed to identify types of precipitation structures irrespective of their physical properties. A 6-month period of 3D reflectivity profiles from the Multi-Radar Multi-Sensor (MRMS) network is used to identify different regimes and investigate their properties with respect to the underlying environmental conditions. Dominant features retrieved from radar reflectivity profiles using convolutional neural-network-based autoencoders are employed to identify similar-looking vertical structures using coupled k-means and agglomerative clustering algorithms. The k-means method identifies distinct groups, while the agglomerative clustering visualizes intercluster relationships. The framework identifies 18 clusters that can be broadly combined into five groups of varied echo-top heights. The 18 clusters demonstrate variability with respect to structural features and precipitation rate/type, implying that profiles in each group belong to a physically different precipitation regime. An independent analysis of the regime properties is conducted by matching the MRMS reflectivity profiles with environmental parameters derived from the High-Resolution Rapid Refresh model forecasts. The distribution of the environmental variables confirms cluster-specific feature properties, confirming the physics-based regime separation across the clusters and their dependence on the vertical structure. The identified precipitation regimes can assist in developing physics-guided retrievals and studying precipitation regimes. Significance Statement: This study proposes a systematic model to identify precipitation profiles of distinct vertical structures and evaluate their dependence on environmental conditions. The model was developed using ground-based radar observations; however, there is potential to extend this model to reflectivity profiles from both ground- and satellite-based sensors. In addition, the identified precipitation regime clusters could be a proxy for the vertical structure of precipitation systems and assist in determining the structural variability within traditional precipitation type classification (e.g., convective versus stratiform). Moreover, identifying the precipitation regimes could also be used to improve satellite-based precipitation retrievals. Finally, a better understanding of precipitation structure would also help improve the initialization of climate models. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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13. The Influence of Morphological Characteristics on the Ball Throwing Velocity in the Professional Handball Players.
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Goranovic, Kosta, Petkovic, Jovica, Joksimovic, Marko, Karisik, Sinisa, and Eler, Nebahat
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HANDBALL players , *VELOCITY , *PERFORMANCE standards , *REFERENCE values , *HANDBALL , *WRIST - Abstract
The aim of this study was to determine influence of upper limbs on the ball throwing velocity. A total of 10 professional handball players (25.74±4.84 years) participated in this study. All of them were playing in the top Montenegrin professional handball league. The results obtained in this study shows that upper limbs have high influence on ball throwing velocity. This study provides normative data and performance standards for professional handball. Coaches can use this information to determine the type of anthropometric characteristics that are needed for handball. Anthropometric parameters such as arm length, wrist diameter, hand length and arm span are the most relevant aspects related to ball throwing speed, given that these parameters cannot be changed through training, they should be taken into account when discovering talents. [ABSTRACT FROM AUTHOR]
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- 2023
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14. The Role of Echocardiography and Cardiac Computed Tomography in Diagnosis of Infective Endocarditis.
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Petkovic, Ana, Menkovic, Nemanja, Petrovic, Olga, Bilbija, Ilija, Radovanovic, Nikola N., Stanisavljevic, Dejana, Putnik, Svetozar, Maksimovic, Ruzica, and Ivanovic, Branislava
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COMPUTED tomography , *ECHOCARDIOGRAPHY , *TRANSESOPHAGEAL echocardiography , *INFECTIVE endocarditis , *DIAGNOSIS methods , *DIAGNOSIS - Abstract
Background: Infective endocarditis (IE) is a rare disease with a high mortality rate and rising incidence, requiring timely and precise diagnosis in order to choose appropriate therapy. Imaging of morphologic lesions is an integrative part of diagnosis. Artifacts and the patient's habitus make echocardiography difficult to visualize advanced-form IE. Cardiac computed tomography (CCT) constantly shows an additive diagnostic value due to high resolution of cardiac anatomy. Conjecturally, joint application of both diagnostic tests improves overall sensitivity and specificity in diagnosing IE. Methods: Patients with definite IE underwent transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and CCT. We analyzed valvular and paravalvular IE lesions in all three imaging methods and compared them to surgical or autopsy findings. We calculated sensitivity, specificity, diagnostic accuracy, and positive and negative predictive value of both imaging tests individually and jointly used. Results: We examined 78 patients, male to female ratio 2:1, mean age 52.29 ± 16.62. We analyzed 85 valves, 70 native valves, 13 prosthetic valves, and 2 corrected valves due to Ozaki procedure, along with a central shunt and 4 pacemaker leads. As a single test, the sensitivity and specificity of CCT, TTE, and TEE for valvular lesions were 91.6/20%, 65.5/57.9%, and 60/84%, and paravalvular lesions were 100/0%, 46/10.5%, and 14.7/100%. When combined together, sensitivity and specificity for valvular lesions rose to 96.6/0% and paravalvular lesions to 100/0%. We also analyzed the diagnostic performance for each test in single and mutual application, per specific IE lesion. Conclusion: In the individual application, CCT in comparison to TTE and TEE shows better diagnostic performance in detection of valvular and paravalvular lesions. In joint application, there is a statistically significant difference in performance compared to their single use, especially in prosthetic valves and invasive forms of IE native valves. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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15. LncRNAs as Regulators of Atherosclerotic Plaque Stability.
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Petkovic, Aleksa, Erceg, Sanja, Munjas, Jelena, Ninic, Ana, Vladimirov, Sandra, Davidovic, Aleksandar, Vukmirovic, Luka, Milanov, Marko, Cvijanovic, Dane, Mitic, Tijana, and Sopic, Miron
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ATHEROSCLEROTIC plaque , *VASCULAR smooth muscle , *ACUTE coronary syndrome , *IMMUNOREGULATION , *LINCRNA , *EXTRACELLULAR matrix , *SMOOTH muscle contraction - Abstract
Current clinical data show that, despite constant efforts to develop novel therapies and clinical approaches, atherosclerotic cardiovascular diseases (ASCVD) are still one of the leading causes of death worldwide. Advanced and unstable atherosclerotic plaques most often trigger acute coronary events that can lead to fatal outcomes. However, despite the fact that different plaque phenotypes may require different treatments, current approaches to prognosis, diagnosis, and classification of acute coronary syndrome do not consider the diversity of plaque phenotypes. Long non-coding RNAs (lncRNAs) represent an important class of molecules that are implicated in epigenetic control of numerous cellular processes. Here we review the latest knowledge about lncRNAs' influence on plaque development and stability through regulation of immune response, lipid metabolism, extracellular matrix remodelling, endothelial cell function, and vascular smooth muscle function, with special emphasis on pro-atherogenic and anti-atherogenic lncRNA functions. In addition, we present current challenges in the research of lncRNAs' role in atherosclerosis and translation of the findings from animal models to humans. Finally, we present the directions for future lncRNA-oriented research, which may ultimately result in patient-oriented therapeutic strategies for ASCVD. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Differential expression of the circadian clock network correlates with tumour progression in gliomas.
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Petkovic, Marina, Yalçin, Müge, Heese, Oliver, and Relógio, Angela
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CIRCADIAN rhythms , *GENE expression , *GLIOMAS , *CLOCK genes , *GLIOBLASTOMA multiforme , *TUMORS , *OVERALL survival - Abstract
Background: Gliomas are tumours arising mostly from astrocytic or oligodendrocytic precursor cells. These tumours are classified according to the updated WHO classification from 2021 in 4 grades depending on molecular and histopathological criteria. Despite novel multimodal therapeutic approaches, the vast majority of gliomas (WHO grade III and IV) are not curable. The circadian clock is an important regulator of numerous cellular processes and its dysregulation had been found during the progression of many cancers, including gliomas. Results: In this study, we explore expression patterns of clock-controlled genes in low-grade glioma (LGG) and glioblastoma multiforme (GBM) and show that a set of 45 clock-controlled genes can be used to distinguish GBM from normal tissue. Subsequent analysis identified 17 clock-controlled genes with a significant association with survival. The results point to a loss of correlation strength within elements of the circadian clock network in GBM compared to LGG. We further explored the progression patterns of mutations in LGG and GBM, and showed that tumour suppressor APC is lost late both in LGG and GBM. Moreover, HIF1A, involved in cellular response to hypoxia, exhibits subclonal losses in LGG, and TERT, involved in the formation of telomerase, is lost late in the GBM progression. By examining multi-sample LGG data, we find that the clock-controlled driver genes APC, HIF1A, TERT and TP53 experience frequent subclonal gains and losses. Conclusions: Our results show a higher level of disrgulation at the gene expression level in GBM compared to LGG, and indicate an association between the differentially expressed clock-regulated genes and patient survival in both LGG and GBM. By reconstructing the patterns of progression in LGG and GBM, our data reveals the relatively late gains and losses of clock-regulated glioma drivers. Our analysis emphasizes the role of clock-regulated genes in glioma development and progression. Yet, further research is needed to asses their value in the development of new treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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17. Risk Factors for Coronary Artery Calcifications in Overweight or Obese Persons with Prediabetes: Can They Predict T2 Diabetes and Coronary Vascular Events?
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Marjanovic Petkovic, Milica, Vuksanovic, Miljanka, Sagic, Dragan, Radovic, Ivana, Soldatovic, Ivan, and Beljic Zivkovic, Teodora
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CORONARY artery calcification , *OVERWEIGHT persons , *PREDIABETIC state , *TYPE 2 diabetes , *GLUCOSE tolerance tests - Abstract
Background: It is difficult to predict the risk of developing atherosclerotic cardiovascular disease in subjects with prediabetes and obesity. The aim of this study was to assess risk factors for coronary artery calcifications (CACs) and the development of type 2 diabetes (T2D) and coronary vascular events (CVEs) after 7 years in 100 overweight or obese persons with prediabetes, according to the baseline coronary artery calcium score (CACS). Methods: Lipids, HbA1c, uric acid, and creatinine were assessed. Glucose, insulin, and c-peptide were determined during an oral glucose tolerance test. Multi-sliced computerized tomography with evaluation of CACS was performed. After 7 years, the subjects were assessed for T2D/CVE. Results: CACs were present in 59 subjects. No single biochemical marker could predict presence of a CAC. After 7 years, T2D developed in 55 subjects (61.8% initially had both IFG and IGT). A gain in weight was the only contributing factor for T2D. Nineteen subjects developed a CVE; increased initial clustering of HOMA-IR > 1.9, LDL > 2.6, and mmol/Land TGL > 1.7 mmol/L and higher CACS were present in that group. Conclusions: No risk factors for CACs could be identified. A gain in weight is associated with T2D development, as are higher CACS and clustering of high LDL+TGL+HOMA-IR with CVEs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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18. Swimming Attenuates Blood Pressure and Oxidative Stress in Hypertensive Rats.
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Petkovic, Anica, Ravic, Marko, Plecevic, Sasa, Jeremic, Jovana, Srejovic, Ivan, Bolevich, Sergey, Rankovic, Goran, Turnic, Tamara Nikolic, Jakovljevic, Vladimir, and Jeremic, Nevena
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SWIMMING , *BLOOD pressure , *OXIDATIVE stress , *HYPERTENSION , *ANTIOXIDANTS - Abstract
Hypertension presents one of the main risk factors for cardiovascular diseases which are the leading cause of morbidity and mortality worldwide. Structural and mechanical changes of the heart and blood vessels as well as overproduction of reactive oxygen species may occur due to the increased blood pressure. Therewith, the goal of our study was to estimate the effects and duration of swimming as a possible therapy approach on blood pressure and oxidative stress parameters in normotensive and hypertensive rats. The study was conducted on 60 male Wistar albino rats divided into two groups, normotensive and hypertensive rats. Each of these groups was divided into three subgroups according to the swimming protocol. The swimming training was kept constant (60 min/day, for five days a week) with two days of rest. After six or nine weeks of the swimming protocol, blood pressure and oxidative stress markers were measured. The control group rats were put in water for one minute a day, in order to avoid water-induced stress. Training significantly reduced systolic blood pressure in hypertensive rats, while diastolic pressure did not change in the group that swam six or nine weeks. The results showed that swimming increases the activity of all measured antioxidative parameters, while values of prooxidants varied depending on the training protocol. Our results confirmed that swimming, as an aerobic exercise, decreases blood pressure and has time-dependent positive system adaptations, especially on the antioxidant parameters. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Unraveling conditions for W-shaped interface and undercooled melts in Cz-Si growth: A smart approach.
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Dropka, Natasha, Petkovic, Milena, Böttcher, Klaus, and Holena, Martin
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DIRECT-fired heaters , *TREE growth , *FLUID flow , *DOPING agents (Chemistry) , *COMPUTER simulation - Abstract
• CFD modeling of Cz-Si growth was used to generate training data. • Data were generated over a wide range of conditions. • Classification trees assessed growth/furnace parameters for W-shaped interfaces and undercooled Si melts. • Symbolic regression predicted minimal temperature in undercooled Si melts. In Cz-Si growth, concave and W-shaped solid–liquid interfaces and undercooled melts are primary contributors to the degradation of crystal quality, particularly structure loss, defect generation, non-uniform dopant distribution, and crystal twisting, making their avoidance crucial. We employed a classification tree machine learning approach to investigate the importance of 15 process and furnace design parameters and their critical ranges for the formation of various types of W-shaped interfaces and undercooled melts at different scales, both in dimensional and dimensionless forms, and across a wide range of process conditions. Moreover, symbolic regression was used to predict minimal melt temperature based on the aforementioned inputs. Training data were obtained by CFD modeling. The classification tree for combined output identified the Grashof, Reynolds for crystal, and Stefan numbers, along with the percentage of silicon solidified, as the most decisive inputs. Symbolic regression for the temperature of undercooled melt highlighted crucible diameter, pulling rate, and the power of the bottom heater as key parameters. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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20. Smart Dimmable LED Lighting Systems †.
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Petkovic, Milica, Bajovic, Dragana, Vukobratovic, Dejan, Machaj, Juraj, Brida, Peter, McCutcheon, Graeme, Stankovic, Lina, and Stankovic, Vladimir
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DAYLIGHT , *LED lamps , *LIGHT emitting diodes , *LUMINOUS flux , *ENERGY consumption , *WINDOW shades - Abstract
This paper proposes energy-efficient solutions for the smart light-emitting diode (LED) lighting system, which provides minimal energy consumption while simultaneously satisfying illuminance requirements of the users in a typical office space. In addition to artificial light from dimmable LED lamps, natural daylight coming from external sources, such as windows, is considered as a source of illumination in an indoor environment. In order to reduce total energy consumption, the smart LED system has the possibility to dim LED lamps, resulting in reduced LED output power. Additionally, various LED lamps' functionality, such as semi-angle of the half illuminance and LED tilting, are introduced as an additional parameter to be optimized to achieve greater energy saving of the designed system. In order to properly exploit external lighting, the idea to reduce overall daylight intensity at a users' location is realized by the option to dim the windows with a shading factor. Based on the users' requirements for a minimal and desired level of illumination, the proposed optimization problems can be solved by implementing different optimization algorithms. The obtained solutions are able to give instructions to a smart LED system to manage and control system parameters (LEDs dimming levels, semi-angles of the half illuminance, orientation of LEDs, the shading factor) in order to design total illumination, which ensures minimal energy consumption and users' satisfaction related to illuminance requirements. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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21. Accuracy Assessment of Simplified Computation of Active and Passive Magnetic Shielding for Optically Pumped Magnetometers.
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Petkovic, Bojana, Ziolkowski, Marek, Kutschka, Hermann, Toepfer, Hannes, and Haueisen, Jens
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MAGNETIC flux density , *MAGNETOMETERS , *FINITE element method , *MAGNETIC field measurements , *MAGNETIC fields - Abstract
A low residual environmental magnetic field is required for the proper operation of most optically pumped magnetometers (OPMs). This is achieved using a combination of passive and active magnetic shielding. Passive magnetic shielding often uses multiple layers of highly permeable materials. A realistic two-layer magnetically shielded room (MSR) for biomagnetic measurements is numerically studied using the finite element method. A measured B-H characteristic of Mumetal is used, which is linearly extrapolated from the Rayleigh region (RR) into the low magnetic field range. This extension of the magnetization curve yields no significant differences compared to using a constant permeability value for the low magnetic field range. Furthermore, we model the MSR with only one shield and apply a simple analytical method of images (MOI). The MOI yields on average a 100-fold reduction in computation time. The relative difference of the magnetic flux density computed with MOI and finite element method (FEM) is smaller than < 1% at the center of a spherical region of interest (ROI) with a radius of 0.3 m desired from the point of magnetoencephalography (MEG) using OPMs. The achieved accuracy of the MOI makes it suitable for the optimization of active shielding coils. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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22. An insight on the post-processing procedure of the Direct Stability Assessment within SGISC.
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Petacco, Nicola, Petkovic, Goran, and Gualeni, Paola
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STABILITY criterion , *FAILURE mode & effects analysis , *FAILURE analysis , *SENSITIVITY analysis - Abstract
In the recent years, the intact stability rule framework witnessed progressive but certain shift towards probabilistic analysis, as already happened in with the damaged stability framework thanks to SOLAS. This paradigm shift is emphasized by introduction of Second Generation Intact Stability criteria (SGISC). This paper implements and renders operational techniques, procedures and indications presented in Direct Stability Assessment (DSA) within SGISC, with a particular focus on pre-process of input data for the assessment, post-process of output data using direct counting method and results presentation. The parametric resonance in following and heading irregular sea stability failure mode has been studied using analysis of probability of failure direct counting procedure for the C11 containership. Besides, a sensitivity analysis on relevant design parameters has been undertaken. The post-processing outcomes have been presented and comments about the expected future role of the DSA are given. • The Direct Stability Assessment in the framework of Second Generation Intact Stability criteria is addressed. • An insight into the available procedure to post-process the results of a direct simulation is given. • The validation procedure of the post-processing method is implemented. • An application case to the C11 containership, considering the parametric rolling stability failure, is presented. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Dual Role of the Arylating Agent in a Highly C(2)-Selective Pd-Catalysed Functionalisation of Pyrrole Derivatives.
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Petkovic, Milos, Jovanovic, Milos, Jovanovic, Predrag, Simic, Milena, Tasic, Gordana, and Savic, Vladimir
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PYRROLE derivatives , *AROMATIC amines , *ALIPHATIC amines , *HETEROCYCLIC compounds , *ARYLATION , *NUCLEOPHILIC reactions - Abstract
Pyrrole derivatives with C(2)-aryl substituents are an important and widespread class of heterocyclic compounds. Their synthesis can be accomplished using several strategic variants which usually entail either protection of the N–H functionality followed by the arylation, or a direct arylation. Although direct arylation is a preferable process due to a reduced number of synthetic steps, it often requires vigorous conditions or challenging reagents. To this synthetic repertoire, we add a novel method that is based on the dual role of the arylating agent. It serves as the nitrogen protecting group while also being involved in the arylation step. Deprotection as a final stage is carried out simultaneously utilising amines as reacting components. This approach ensures relatively mild conditions and exclusive C(2) selectivity yielding 2-arylpyrroles with the amide functionality. While aromatic amines are not suitable partners under studied conditions, most likely due to lower nucleophilicity, aliphatic amines, either primary or secondary, afford products in good yields. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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24. Deep learning for spatio‐temporal supply and demand forecasting in natural gas transmission networks.
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Petkovic, Milena, Koch, Thorsten, and Zittel, Janina
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DEMAND forecasting , *DEEP learning , *CONVOLUTIONAL neural networks , *NATURAL gas pipelines , *GAS flow , *NATURAL gas , *POWER resources - Abstract
Germany is the largest market for natural gas in the European Union, with an annual consumption of approx. 95 billion cubic meters. The German high‐pressure gas pipeline network's length is roughly 40 000 km, which enables highly fluctuating quantities of gas to be transported safely over long distances. Considering that similar amounts of gas are also transshipped through Germany to other EU states, it is clear that Germany's gas transport system is essential to the European energy supply. Since the average velocity of gas in a pipeline is only 25 km/h, an adequate high‐precision, high‐frequency forecasting of supply and demand is crucial for efficient control and operation of such a transmission network. We propose a deep learning model based on spatio‐temporal convolutional neural networks (DLST) to tackle the problem of gas flow forecasting in a complex high‐pressure transmission network. Experiments show that our model effectively captures comprehensive spatio‐temporal correlations through modeling gas networks and consistently outperforms state‐of‐the‐art benchmarks on real‐world data sets by at least 15%. The results demonstrate that the proposed model can deal with complex nonlinear gas network flow forecasting with high accuracy and effectiveness. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. Osteoporosis management and falls prevention in patients with haemophilia: Review of haemophilia guidelines.
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Petkovic, Madison J., Tran, Huyen A, Ebeling, Peter R., and Zengin, Ayse
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ACCIDENTAL fall prevention , *HEMOPHILIA , *BONE health , *BONE density , *OSTEOPOROSIS , *BONE fractures - Abstract
Introduction: Patients with haemophilia (PWH) have a high prevalence of osteoporosis, falls and fractures at all ages. The role of haemophilia itself may contribute to low bone mineral density (BMD) due to coagulation factor deficiency. Guidelines for the management of osteoporosis, fracture and fall risk may help to reduce fracture and fall risk, and delay osteoporosis onset. Aim: We aim to review current haemophilia guidelines regarding osteoporosis prevention, screening, diagnosis and management, and fall prevention. Method: A database search (Ovid MEDLINE) revealed two haemophilia guidelines (World and British) published within the last ten years. Local Australian haemophilia guidelines were identified through a manual search. Results: All haemophilia guidelines were found to contain inadequate recommendations for osteoporosis management and fall prevention due to a lack of evidence in the literature. Conclusion: Further studies are required to assess the trajectory of bone health in PWH, the mechanism of bone loss in PWH, and the effectiveness of weight‐bearing exercises, interventions for fall prevention, screening programmes, and use of anti‐osteoporosis medications in PWH across the lifecourse. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. Increased risk for thromboembolic events from combination of a gynecologic malignancy with severe acute respiratory syndrome coronavirus 2 infection: a case report.
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Stefan, Alexandra, Petkovic, Marija, König, Alexander, Koch, Julian, Hagemann, Friederike, Wuerstlein, Rachel, Harbeck, Nadia, Mahner, Sven, and Kaltofen, Till
- Abstract
Purpose: During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature.Case Report: A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later.Methods: We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles.Results: We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor.Conclusion: Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required. [ABSTRACT FROM AUTHOR]- Published
- 2022
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27. JOHN B. GREEN, SUBMARINE DIVER, AND EARLY SALVAGE DIVING IN LAKE ERIE .
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Petkovic, Erik A.
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DIVING , *FOOT , *SAILBOATS , *NAVAL architecture , *LAKES , *OCEANOGRAPHIC submersibles - Published
- 2022
28. Rate of Force Development and Stretch-Shortening Cycle in Different Jumps in the Elite Volleyball Players.
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Goranovic, Kosta, Petkovic, Jovica, Hadzic, Rasid, and Joksimovic, Marko
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VOLLEYBALL players , *KNEE , *ANKLE , *ANKLE injuries , *OVERUSE injuries , *GROUND reaction forces (Biomechanics) , *IMPACT loads - Abstract
As it is currently played, volleyball is a game in which success depends in large measure on the athleticism of the participants. The aim of this research was to point out the importance of the cycle of stretching and shortening in different jumps for elite volleyball players. Thus, it is common for volleyball athletes to place considerable emphasis on jump training. Not surprisingly, overload injuries of the knee and ankle joints, both acute and chronic, occur frequently among volleyball players and are related to the volume of jump training and skill repetition. Understanding the biomechanics of jumping is therefore a prerequisite for designing effective training programs which minimize the risk of overuse injuries that may result from excessive jumping, and the repetitive mechanical loading of muscles and joints that are involved in jump training Muscles acting about a joint function naturally through a combination of eccentric (lengthening) and concentric (shortening) activations. In the lower limb, the stretch-shortening cycle is a reflex arc in which the tendomuscular system acting about the knee or ankle is eccentrically preloaded (stretched) in the loading or impact phase of the jump before concentrically shortening in the push-off or take-off phase. [ABSTRACT FROM AUTHOR]
- Published
- 2022
29. Circular versus linear RNA topology: different modes of RNA–RNA interactions in vitro and in human cells.
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Petkovic, Sonja, Graff, Sarah, Feller, Nina, Berghaus, Julia, Ruppert, Vanessa-Patricia, Dülfer, Jasmin, and Sczakiel, Georg
- Published
- 2021
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30. Impact of the bronchopulmonary sequestration on endobronchial tuberculosis: the case report and the review of literature.
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Adzic-Vukicevic, Tatjana, Petkovic, Ana, Menkovic, Nemanja, Stosic, Maja, Bracanovic, Milos, Korica, Stefan, and Barac, Aleksandra
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COUGH , *COMPUTED tomography , *MEDICAL personnel , *VENA cava inferior , *ATELECTASIS , *TUBERCULOSIS , *LUNGS - Abstract
Introduction: We describe the rare case of endobronchial tuberculosis (EBTB) and chronic pulmonary atelectasis with mediastinal distortion. Finding of the concomitant venous anomaly of inferior vena cava revealed the diagnosis of bronchopulmonary sequestration. Case Report: A 22-year-old Caucasian woman presented with a history of chronic cough, initially treated as bronchial asthma for a year. Chest X-ray showed fibrocaseous cavernous tuberculosis on the right lung. Acid Fast Bacilli (AFB) were found in sputum samples. Patient was treated for 6 months with usual antituberculous regiment. Control chest X-ray showed subatelectasis of the upper right lobe. Six months later the first thorax computed tomography (CT) showed complete atelectasis of the right lung. Patient was admitted to the hospital again after 6 years due to the persistent fever and cough. Endoscopic finding and histopathological analysis confirmed EBTB. Thoracic CT scan revealed duplication of inferior vena cava which led to profound vascular analysis and aberrant arterial vascularization of aortic origin that contributed to the diagnosis of bronchopulmonary sequestrations. Antituberculous treatment was initiated (streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide) and lasted for 8 months. After 8 months a follow-up fiberoptic bronchoscopy showed the progression of endoscopic finding with 60-70% tracheal stenosis. Histopathological finding of the mid-trachea showed non-specific granulations. During 7 years of follow-up repeated bronchoscopy and thoracic CT scans were unchanged and patient was well-shaped. Conclusions: The clinician should consider bronchopulmonary sequestration in the cases of recurrent EBTB. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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31. Phytochemical and Pharmacological Properties of Some Species of the Genus Galium L. (Galium verum and mollugo).
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Bradic, Jovana, Petkovic, Anica, and Tomovic, Marina
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ESSENTIAL oils , *SPECIES , *HERBACEOUS plants , *PHENOLS , *BIOACTIVE compounds , *MARINE natural products - Abstract
Galium verum L. and Galium mollugo L. are perennial herbaceous plants, belonging to the Rubiaceae family. Several classes of bioactive compounds, such as iridoid glycosides, phenolic compounds, anthraquinones and triterpenes, as well as small amounts of tannins, saponins, essential oils have been isolated from Galium species so far. Plants belonging to this genus have a long history of use in a traditional medicine for the treatment of many diseases and conditions. The main application of G. verum is as diuretic, choleretic and as the treatment for gout and epilepsy. On the other hand, G. mollugo has been used to treat hysteria, epilepsy, as vulnerary. Over the past decades, numerous papers have been published referring to the chemical constituents presented in G. verum and G. mollugo extracts. Additionally, chemical composition and pharmacological effects of G. verum have been investigated, however data related to the effects of G. mollugo is limited. In this review, we summarized the current knowledge on the phytochemical and pharmacological properties of G. verum and G. mollugo. Finally, we proposed directions for future research in this field, which can improve our understanding of the potential health benefits of Galium species. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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32. Genotype–Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review.
- Author
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Wittke, Christina, Petkovic, Sonja, Dobricic, Valerija, Schaake, Susen, Arzberger, Thomas, Compta, Yaroslau, Englund, Elisabet, Ferguson, Leslie W., Gelpi, Ellen, Roeber, Sigrun, Giese, Armin, Grossman, Murray, Irwin, David J., Meissner, Wassilios G., Nilsson, Christer, Pantelyat, Alexander, Rajput, Alex, Swieten, John C., Troakes, Claire, and Respondek, Gesine
- Abstract
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap‐aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%–86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ‐1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10−12) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57–70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. DEATH OF A U-BOAT.
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Petkovic, Erik A. Sr.
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WORLD War II , *DEPTH charges , *NAZIS ,GERMAN submarines - Abstract
The article discusses the sinking of German Submarine U-352, in World War II. Topics including World War II U-boat design was rooted in the successes of earlier models from the Great War, when Germans had perfected methods of submarine warfare that were a substantial threat to Great Britain; U.S. Coast Guard Thetis-class cutter Icarus was ordered from Staten Island, New York, to Key West, Florida, to escort ships along the Eastern Sea Frontier.
- Published
- 2022
34. Experts prioritize osteoarthritis non-surgical interventions from Cochrane systematic reviews for translation into "Evidence4Equity" summaries.
- Author
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Houlding-Braunberger, Elizabeth, Petkovic, Jennifer, Lebel, Nicholas, and Tugwell, Peter
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OSTEOARTHRITIS treatment , *MEDICAL databases , *INFORMATION storage & retrieval systems , *HEALTH services accessibility , *SYSTEMATIC reviews , *EVIDENCE-based medicine , *HEALTH status indicators , *SOCIOECONOMIC factors , *PHYSICAL activity , *HEALTH literacy , *EXERCISE , *TRANSLATIONAL research , *THEMATIC analysis - Abstract
Objective: Osteoarthritis generates substantial health and socioeconomic burden, which is particularly marked in marginalized groups. It is imperative that practitioners have ready access to summaries of evidence-based interventions for osteoarthritis that incorporate equity considerations. Summaries of systematic reviews can provide this. The present study surveyed experts to prioritize a selection ofinterventions, from which equity focused summaries will be generated. Specifically, the prioritized interventions will be developed into Cochrane Evidence4Equity (E4E) summaries. Methods: Twenty-seven systematic reviews of OA interventions were found. From these, twenty-nine non-surgical treatments for osteoarthritis were identified, based on statistically significant findings for desired outcome variables or adverse events. Key findings from these studies were summarised and provided to 9 experts in the field of osteoarthritis.. Expert participants were asked to rate interventions based on feasibility, health system effects, universality, impact on inequities, and priority for translation into equity based E4E summaries. Expert participants were also encouraged to make comments to provide context for each rating. Free text responses were coded inductively and grouped into subthemes and themes. Results: Expert participants rated the intervention home land-based exercise for knee OA highest for priority for translation into an E4E summaries, followed by the interventions individual land-based exercise for knee OA, class land-based exercise for knee OA, exercise for hand OA and land-based exercise for hip OA. Upon qualitative analysis of the expert participants' comments, fifteen subthemes were identified and grouped into three overall themes: (1) this intervention or an aspect of this intervention is unnecessary or unsafe; (2) this intervention or an aspect of this intervention may increase health inequities; and (3) experts noted difficulties completing rating exercise. Conclusion: The list of priority interventions and corresponding expert commentary generated information that will be used to direct and support knowledge translation efforts. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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35. Polycyclic Compounds from Allenes via Palladium-Mediated Intramolecular Carbopalladation/Nucleophilic Substitution Cascade Processes.
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Jovanovic, Milos D., Petkovic, Milos R., and Savic, Vladimir M.
- Subjects
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POLYCYCLIC compounds , *ALLENE , *ORGANIC synthesis , *TRANSITION metals , *PALLADIUM , *NATURAL products - Abstract
In recent decades transition metals have made a substantial contribution to the development of novel synthetic processes, with palladium catalysis being, arguably, at the forefront of this research. The efficiency of Pd-promoted C–C or C–X bond formation along with a variety of other transformations renders this metal an indispensable tool in synthetic organic chemistry. Of particular interest are Pd-catalysed multicomponent cascade reactions as they often allow the creation of complex structures from relatively simple starting materials, mimicking in this sense biochemical processes. Allenes as partners in Pd-promoted cascades involving carbopalladation/nucleophilic substitutions have been extensively studied in recent years. Many tactical variants have been explored showing a high level of efficiency and chemoselectivity with predictable outcomes. This short review is focused on intramolecular processes of this type because they provide access to relatively complex polycyclic products, possessing structural features often found in natural products and related compounds. Various approaches are discussed with the intention to demonstrate their applicability and synthetic potential. 1 Introduction 2 Intramolecular Palladium-Promoted Cascades of Allenes 3 Class I Cyclisations 4 Class II Cyclisations 5 Class III Cyclisations 6 Class IV Cyclisations 7 Conclusion [ABSTRACT FROM AUTHOR]
- Published
- 2021
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36. Improving Oxidative Stability of Cosmetic Emulsions with Plant Extracts: Current Status and Potential.
- Author
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PETKOVIC, ANICA, JAKOVLJEVIC, VLADIMIR, TOMOVIC, MARINA, JEREMIC, JOVANA, RISTIC, GORDANA, and BRADIC, JOVANA
- Subjects
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EMULSIONS , *OXIDATION , *CHEMICAL stability , *PLANT extracts , *CHEMISTRY of cosmetics - Abstract
There are increasing demands for cosmetic emulsions with natural active components such as plant extracts because of their myriad benefits. Quality of cosmetic emulsions may be affected by distribution and storage processes, which can lead to peroxidation of lipid components. Lipid peroxidation results in undesirable alterations in efficacy, texture, and appearance of the cosmetic product, thus indicating a need to find a safe and potent compound to be added in products to postpone oxidation processes. In that sense, the current article gives an overview of parameters influencing oxidative stability of emulsions, as well as methods for assessing the oxidative stability. Emphasis is given to the usage of plant extracts rich in phenolics for improving oxidative stability of cosmetic emulsions. Application of plant extracts in cosmetic emulsion is promising because of their significant antioxidant properties which may delay lipid peroxidation during storage. Plant species are a valuable source of biologically active compounds that might be exploited in the cosmetic and pharmaceutical industry. [ABSTRACT FROM AUTHOR]
- Published
- 2021
37. Self-Generated Hypoxia Leads to Oxidative Stress and Massive Death in Ustilago maydis Populations under Extreme Starvation and Oxygen-Limited Conditions.
- Author
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Petkovic, Jelena, Kojic, Milorad, and Milisavljevic, Mira
- Subjects
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HYPOXEMIA , *OXIDATIVE stress , *USTILAGO maydis , *SACCHAROMYCES cerevisiae , *REACTIVE oxygen species - Abstract
Ustilago maydis and Saccharomyces cerevisiae differ considerably in their response to watertransfer treatments. When stationary phase cells were transferred to pure water and incubated under limited supply of oxygen, the U. maydis cells suffered a catastrophic loss of viability while the S. cerevisiae population was virtually unaffected by the treatment. The major factor underlying the death of the U. maydis cells under those conditions was an oxygen-consuming cellular activity that generated a hypoxic environment, thereby inducing oxidative stress and accumulation of reactive oxygen species, which resulted in lethality. Importantly, a small residue of U. maydis cells that did survive was able to resume growth and repopulate up to the initial culture density when sufficient aeration was restored. The regrowth was dependent on the cellular factors (Adr1, Did4, Kel1, and Tbp1), previously identified as required for repopulation, after killing with hydrogen peroxide. Surprisingly, the survivors were also able to resume growth under apparently hypoxic conditions, indicating that these remnant cells likely switched to a fermentative mode of growth. We discuss the findings in terms of their possible relevance to the eco-evolutionary adaptation of U. maydis to risky environments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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38. Sensitive quantification of α-glucans in mouse tissues, cell cultures, and human cerebrospinal fluid.
- Author
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Nitschke, Silvia, Petkovic, Sara, Ahonen, Saija, Minassian, Berge A., and Nitschke, Felix
- Subjects
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CEREBROSPINAL fluid , *CELL culture , *GLYCOGEN storage disease , *CEREBROSPINAL fluid examination , *ENZYME metabolism , *GLYCOGEN , *SKELETAL muscle - Abstract
The soluble α-polyglucan glycogen is a central metabolite enabling transient glucose storage to suit cellular energy needs. Glycogen storage diseases (GSDs) comprise over 15 entities caused by generalized or tissue-specific defects in enzymes of glycogen metabolism. In several, e.g. in Lafora disease caused by the absence of the glycogen phosphatase laforin or its interacting partner malin, degradation-resistant abnormally structured insoluble glycogen accumulates. Sensitive quantification methods for soluble and insoluble glycogen are critical to research, including therapeutic studies, in such diseases. This paper establishes methodological advancements relevant to glycogen metabolism investigations generally, and GSDs. Introducing a pre-extraction incubation method, we measure degradation-resistant glycogen in as little as 30 mg skeletal muscle or a single hippocampus from Lafora disease mouse models. The digestion-resistant glycogen correlates with the disease-pathogenic insoluble glycogen and can readily be detected in very young mice where glycogen accumulation has just begun. Secondly, we establish a high-sensitivity glucose assay with detection of ATP depletion, enabling 1) quantification of α-glucans in cell culture using a medium-throughput assay suitable for assessment of candidate glycogen synthesis inhibitors, and 2) discovery of α-glucan material in healthy human cerebrospinal fluid, establishing a novel methodological platform for biomarker analyses in Lafora disease and other GSDs. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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39. Reporting of health equity considerations in cluster and individually randomized trials.
- Author
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Petkovic, Jennifer, Jull, Janet, Yoganathan, Manosila, Dewidar, Omar, Baird, Sarah, Grimshaw, Jeremy M., Johansson, Kjell Arne, Kristjansson, Elizabeth, McGowan, Jessie, Moher, David, Petticrew, Mark, Robberstad, Bjarne, Shea, Beverley, Tugwell, Peter, Volmink, Jimmy, Wells, George A., Whitehead, Margaret, Cuervo, Luis Gabriel, White, Howard, and Taljaard, Monica
- Subjects
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CLUSTER randomized controlled trials , *RACE , *POPULATION health , *RANDOMIZED controlled trials - Abstract
Background: The randomized controlled trial (RCT) is considered the gold standard study design to inform decisions about the effectiveness of interventions. However, a common limitation is inadequate reporting of the applicability of the intervention and trial results for people who are "socially disadvantaged" and this can affect policy-makers' decisions. We previously developed a framework for identifying health-equity-relevant trials, along with a reporting guideline for transparent reporting. In this study, we provide a descriptive assessment of health-equity considerations in 200 randomly sampled equity-relevant trials.Methods: We developed a search strategy to identify health-equity-relevant trials published between 2013 and 2015. We randomly sorted the 4316 records identified by the search and screened studies until 100 individually randomized (RCTs) and 100 cluster randomized controlled trials (CRTs) were identified. We developed and pilot-tested a data extraction form based on our initial work, to inform the development of our reporting guideline for equity-relevant randomized trials.Results: In total, 39 trials (20%) were conducted in a low- and middle-income country and 157 trials (79%) in a high-income country focused on socially disadvantaged populations (78% CRTs, 79% RCTs). Seventy-four trials (37%) reported a subgroup analysis across a population characteristic associated with disadvantage (25% CRT, 49% RCTs), with 19% of included studies reporting subgroup analyses across sex, 9% across race/ethnicity/culture, and 4% across socioeconomic status. No subgroup analyses were reported for place of residence, occupation, religion, education, or social capital. One hundred and forty-one trials (71%) discussed the applicability of their results to one or more socially disadvantaged populations (68% of CRT, 73% of RCT).Discussion: In this set of trials, selected for their relevance to health equity, data that were disaggregated for socially disadvantaged populations were rarely reported. We found that even when the data are available, opportunities to analyze health-equity considerations are frequently missed. The recently published equity extension of the Consolidated Reporting Standards for Randomized Trials (CONSORT-Equity) may help improve delineation of hypotheses related to socially disadvantaged populations, and transparency and completeness of reporting of health-equity considerations in RCTs. This study can serve as a baseline assessment of the reporting of equity considerations. [ABSTRACT FROM AUTHOR]- Published
- 2020
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40. Evaluation of V05 Precipitation Estimates from GPM Constellation Radiometers Using KuPR as the Reference.
- Author
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You, Yalei, Petkovic, Veljko, Tan, Jackson, Kroodsma, Rachael, Berg, Wesley, Kidd, Chris, and Peters-Lidard, Christa
- Subjects
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METEOROLOGICAL precipitation , *MICROWAVE radiometers , *RADIOMETERS , *ESTIMATES , *HUMIDITY , *REMOTE sensing - Abstract
This study assesses the level-2 precipitation estimates from 10 radiometers relative to Global Precipitation Measurement (GPM) Ku-band precipitation radar (KuPR) in two parts. First, nine sensors—four imagers [Advanced Microwave Scanning Radiometer 2 (AMSR2) and three Special Sensor Microwave Imager/Sounders (SSMISs)] and five sounders [Advanced Technology Microwave Sounder (ATMS) and four Microwave Humidity Sounders (MHSs)]—are evaluated over the 65°S–65°N region. Over ocean, imagers outperform sounders, primarily due to the usage of low-frequency channels. Furthermore, AMSR2 is clearly superior to SSMISs, likely due to the finer footprint size. Over land all sensors perform similarly except the noticeably worse performance from ATMS and SSMIS-F17. Second, we include the Sondeur Atmospherique du Profil d'Humidite Intertropicale par Radiometrie (SAPHIR) into the evaluation process, contrasting it against other sensors in the SAPHIR latitudes (30°S–30°N). SAPHIR has a slightly worse detection capability than other sounders over ocean but comparable detection performance to MHSs over land. The intensity estimates from SAPHIR show a larger normalized root-mean-square-error over both land and ocean, likely because only 183.3-GHz channels are available. Currently, imagers are preferred to sounders when level-2 estimates are incorporated into level-3 products. Our results suggest a sensor-specific priority order. Over ocean, this study indicates a priority order of AMSR2, SSMISs, MHSs and ATMS, and SAPHIR. Over land, SSMIS-F17, ATMS and SAPHIR should be given a lower priority than the other sensors. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
41. Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation.
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Petkovic, Jennifer, Riddle, Alison, Akl, Elie A., Khabsa, Joanne, Lytvyn, Lyubov, Atwere, Pearl, Campbell, Pauline, Chalkidou, Kalipso, Chang, Stephanie M., Crowe, Sally, Dans, Leonila, Jardali, Fadi El, Ghersi, Davina, Graham, Ian D., Grant, Sean, Greer-Smith, Regina, Guise, Jeanne-Marie, Hazlewood, Glen, Jull, Janet, and Katikireddi, S. Vittal
- Subjects
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STAKEHOLDER theory , *GUIDELINES , *META-analysis , *CONFLICT of interests , *COMPUTER surveys - Abstract
Background: Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. Methods: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. Discussion: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
42. Proline Derived Bicyclic Derivatives through Metal Catalysed Cyclisations of Allenes: Synthesis of Longamide B, Stylisine D and their Derivatives.
- Author
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Jovanovic, Milos, Petkovic, Milos, Jovanovic, Predrag, Simic, Milena, Tasic, Gordana, Eric, Slavica, and Savic, Vladimir
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PROLINE , *ALLENE , *METALS , *TRANSITION metals , *PALLADIUM - Abstract
Annulations of allene‐substituted proline derivatives promoted by transition metals have been investigated as a general way to access bicyclic structures with a bridgehead nitrogen. Two processes, Pd‐ and Ag‐catalysed cyclisations, have been employed complementary to control the substitution pattern of the product. The investigated methodologies afforded the bicyclic derivatives in comparable yields, while Ag‐catalysis showed higher level of diastereoselectivity. Both processes have been utilized in the synthesis of naturally occurring pyrroles longamide B, stylisine D and their derivatives. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
43. Three Component Cascade Processes Involving Palladium Catalyzed Transformations/Dipolar Cycloadditions for the Synthesis of Angular Heterotriquinane Derivatives.
- Author
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Jovanovic, Predrag, Jovanovic, Milos, Petkovic, Milos, Simic, Milena, Tasic, Gordana, Rodic, Marko, Rakic, Srdjan, Vlahovic, Filip, and Savic, Vladimir
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RING formation (Chemistry) , *ALLENE , *PALLADIUM , *OXIMES , *CYCLOHEXANONES - Abstract
Combining chemical reactivities of allenes and oximes created a methodology for the preparation of heterocyclic triquinane‐type skeletons via a cascade process constructing four bonds in a single step. The initial reaction of allene moiety promoted by Pd‐catalysis, affording π‐allyl Pd‐species, was followed by two additional transformations ‐ nucleophilic displacement and dipolar cycloaddition ‐ to furnish the product highly stereoselectively in moderate to good yields. For the process to be efficient, it was necessary to use a dipolarophilic component as a solvent. Intriguingly, while the reaction with cyclopentanone derived oxime progressed through the whole cascade, with cyclohexanone analogue it stopped at the nitrone stage, requiring an additional step to yield similar type of products. Some aspects of the studied cascade were examined by DFT. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Successful pregnancies in a patient with Takayasu arteritis and antiphospholipid syndrome, maintained on infliximab corticosteroid-free regimen: case-based review.
- Author
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Jovicic, Zikica, Dragasevic, Sanja, Petkovic, Ana, Plesinac, Snezana, Sokic Milutinovic, Aleksandra, and Stojanovic, Maja
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ANTIPHOSPHOLIPID syndrome , *TAKAYASU arteritis , *CROHN'S disease , *PREGNANCY outcomes , *PHOSPHOLIPID antibodies , *LITERATURE reviews - Abstract
Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Lorentz Force Surface Integration Method: Calculation of Lorentz Force by Means of Surface Integrals.
- Author
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Petkovic, B., Dolker, E. M., Schmidt, R., Toepfer, H., and Haueisen, J.
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LORENTZ force , *SURFACE forces , *PERMANENT magnets , *MAGNETIC dipoles , *INTEGRALS - Abstract
We propose a novel way of calculating the Lorentz force acting on a permanent magnet when moved relative to a conducting specimen which we call the Lorentz force surface integration method. We derive surface integrals and solutions for these integrals for the Lorentz force computation, which are valid for any geometry of the conducting specimen, movement direction, position, and orientation of the magnet. We exemplify our approach on a parallelepipedical specimen and a magnetic dipole, where we obtain normalized root-mean-square errors below 0.6% with respect to a reference finite-element solution. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
46. Sex increases the probability of evolutionary rescue in the presence of a competitor.
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Petkovic, Nikola and Colegrave, Nick
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ABIOTIC environment , *ASEXUAL reproduction , *GENDER , *SPERM competition , *CHLAMYDOMONAS reinhardtii , *NATURAL selection , *COMPETITION (Biology) - Abstract
The explanation for the continued existence of sex, despite its many costs, remains one of the major challenges of evolutionary biology. Previous experimental studies have demonstrated that sex increases the rate of adaptation in novel environments relative to asexual reproduction. Whereas these studies have investigated the impact of sex on adaptation to stressful abiotic environments, the potential for biotic interactions to influence this advantage of sex has been largely ignored. Species rarely exist in isolation in natural conditions, so the impact of sex on adaptation to a stressful abiotic environment may be altered by the interactions between coexisting species. To investigate the interplay of sex and competition on adaptation to deteriorating conditions, we allowed populations of the unicellular alga (Chlamydomonas reinhardtii) to evolve in an environment to which they were initially poorly adapted. We manipulated both their mode of reproduction and the presence of a competitor, and monitored population size and proportion of evolutionary rescue events for each mode of reproduction. The results indicate that sex may be the beneficial strategy in the presence of the competitor. Sexual populations had highest probability of evolutionary rescue irrespective of the presence of the competitor. The overall advantage of sex was also manifested through higher level of adaptedness of survived sexual populations relative to asexual populations. Since competitive interactions are commonplace in nature, one of the explanations for the maintenance of sex by natural selection may be the increased rate of adaptation of sexual populations both in the presence and absence of competitors. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
47. Stereocontrolled Synthesis of Highly Substituted trans α,β‐Unsaturated Ketones with Potent Anticancer Properties from Glycals.
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Jovanovic, Predrag, Petkovic, Milos, Simic, Milena, Jovanovic, Milos, Tasic, Gordana, Crnogorac, Marija Djordjic, Zizak, Zeljko, and Savic, Vladimir
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KETONES , *GLYCALS - Abstract
A novel synthetic route for highly substituted conjugated ketones has been developed utilizing glycals as starting materials. The two‐step process combined the Heck reaction/Lewis acid promoted ring opening to afford the products in 33–80 % overall yields and with a high level of trans stereoselectivity. Since the products are essentially the aldols, this methodology may be employed in some cases as an alternative synthetic route to the typical aldol condensation. Densely substituted, selectively protected conjugated ketones are synthetically attractive structures which, in our case, proved to be biologically equally appealing. Namely, they showed activity against several cancer cell lines, such as HeLa, K562, MDA‐MB‐453, in some instances overperforming cisplatin used as a standard. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
48. Novel kinetics model for adsorption of pollutant from wastewaters onto zeolites. Kinetics of phenol adsorption on zeolite-type silicalite.
- Author
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Petkovic, Sandra, Adnadjevic, Borivoj, and Jovanovic, Jelena
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ADSORPTION kinetics , *POLLUTANTS , *ACTIVATION energy , *SILICALITE , *PHENOL , *CRYSTALLIZATION - Abstract
The kinetics of isothermal adsorption of phenol from an aqueous solution onto the zeolite-type silicalite was investigated. Zeolite-type silicalite was synthesized and its basic physico-chemical properties were determined. Isothermal adsorption kinetics curves of phenol on zeolite-type silicalite were measured at temperature range from 283 to 313 K. By applying Friedman's differential isoconversional method it was found that the adsorption of phenol on silicalite has one rate determining step. By using the 'model-fitting' method it was established that the kinetic of adsorption can be described with theoretical kinetic model of the two-dimensional phase-boundary controlled reaction (model R2). The kinetic parameters, activation energy ( E a = 45 kJ mol − 1 ) and preexponetial factor (lnA = 14.1 min−1) of phenol adsorption were calculated. The thermodynamic parameters, standard enthalpy (Δ H *), standard entropy (Δ S *) and standard free Gibbs energy of adsorption (Δ G *) were calculated and discussed. A novel model for the kinetics of pollutant adsorption from wastewaters onto zeolites based on the following: zeolite pores have cylindrical shape with average radius r 0, pores in zeolite are filled simultaneously by the model 'layer by layer', the rate of phenol adsorption is higher than the rate of the growth of the thickness of the adsorption layer was suggested. It has been found that the adsorption kinetics can be completely described by this kinetic model. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
49. Error rate and ergodic capacity of RF-FSO system with partial relay selection in the presence of pointing errors.
- Author
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Petkovic, Milica I., Ansari, Imran Shafique, Djordjevic, Goran T., and Qaraqe, Khalid A.
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RADIO frequency , *FREE-space optical technology , *RAYLEIGH fading channels , *ATMOSPHERIC turbulence , *SIGNAL-to-noise ratio , *MONTE Carlo method - Abstract
Abstract This paper presents an analysis of a multiple dual-hop relaying system, which is composed of km-class radio frequency (RF)-free-space optical (FSO) links. Partial relay selection based on outdated channel state information (CSI) is employed in order to select active relay for further transmission. Amplify-and-forward relaying protocol is utilized. The RF links are assumed to be subject to Rayleigh fading, and the FSO links are influenced by both Gamma–Gamma atmospheric turbulence and pointing errors. On the basis of our previously derived expression for cumulative distribution function of the equivalent signal-to-noise ratio of the whole system, we derive novel analytical expressions for the average bit-error rate (BER) and ergodic capacity that are presented in terms of the Meijer's G -function and extended generalized bivariate Meijer's G -function, respectively. The numerical results are confirmed by Monte Carlo simulations. Considering the effect of time-correlation between outdated CSI and actual CSI related to the RF channel at the time of transmission, the average BER and the ergodic capacity dependence on various system and channel parameters are observed and discussed. The results illustrate that the temporal correlation between outdated and actual CSI has strong effect on system performance, particularly on BER values, when FSO hop is influenced by favorable conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
50. Insulin Receptor and Glucose Transporters in the Mammalian Cochlea.
- Author
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Huerzeler, Nathan, Petkovic, Vesna, Sekulic-Jablanovic, Marijana, Kucharava, Krystsina, Wright, Matthew B., Bodmer, Daniel, and Wright, Matthew B
- Subjects
- *
INSULIN receptors , *GLUCOSE transporters , *CORTI'S organ , *COCHLEA , *HAIR cells , *BASILAR membrane - Abstract
Insulin receptors are expressed on nerve cells in the mammalian brain, but little is known about insulin signaling and the expression of the insulin receptor (IR) and glucose transporters in the cochlea. We performed immunohistochemistry and gene/protein expression analysis to characterize the expression pattern of the IR and glucose transporters in the mouse organ of Corti (OC). We also performed glucose uptake assays to explore the action of insulin and the effects of pioglitazone, an insulin sensitizer, on glucose transport in the OC. Western blots of protein extracts from OCs showed high expression of IR and glucose transporter 3 (GLUT3). Immunohistochemistry demonstrated that the IR is specifically expressed in the supporting cells of the OC. GLUT3 was found in outer and inner hair cells, in the basilar membrane (BM), the stria vascularis (SV), Reissner's membrane and spiral ganglion neurons (SGN). Glucose transporter 1 (GLUT1) was detected at low levels in the BM, SV and Reissner's membrane, and showed high expression in the SGN. Fluorescence glucose uptake assays revealed that hair cells take up glucose and that addition of insulin (10 nM or 1 µM) approximately doubled the rate of uptake. Pioglitazone conferred a small but nonsignificant potentiation of glucose uptake at the highest concentration of insulin. Gene expression analysis confirmed expression of IR, GLUT1 and GLUT3 mRNA in the OC. Pioglitazone significantly upregulated IR and GLUT1 mRNA expression, which was further increased by insulin. Together, these data show that insulin-stimulated glucose uptake occurs in the OC and may be associated with upregulation of both the IR and GLUT1. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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