bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Impact of 18F-FDG PET/CT in the Diagnostic Workup of Pancreatic Ductal Adenocarcinoma: A Systematic Review
Authors: Arnone Annachiara , Laudicella Riccardo , Caobelli Federico , Guglielmo Priscilla , Spallino Marianna , Abenavoli Elisabetta , Martini Anna , Filice Rossella , Comis Alessio , Cuzzocrea Marco , Linguanti Flavia , Evangelista Laura , Alongi Pierpaolo
Published: December 2020

In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 patients and index test (i.e., “FDG” or “18F-FDG” AND “pancreatic adenocarcinoma” or “pancreas cancer” AND “PET” or “positron emission tomography”). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients’ characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC.
Feasibility and Reproducibility of Left Atrium Measurements Using Different Three-Dimensional Echocardiographic Modalities
Authors: Motoc Andreea , Roosens Bram , Scheirlynck Esther , Tanaka Kaoru , Luchian Maria Luiza , Magne Julien , Mandoli Giulia Elena , Hinojar Rocio , Cameli Matteo , Zamorano Jose Luis , Droogmans Steven , Cosyns Bernard
Published: December 2020

Left atrium (LA) volume is a biomarker of cardiovascular outcomes. Three-dimensional echocardiography (3DE) provides an accurate LA evaluation, but data regarding the optimal 3DE method is scarce. We assessed the feasibility and reproducibility of LA measurements using different 3DE methods. One hundred and ninety-four patients were prospectively analyzed. Conventional 3DE and two semi-automatic 3DE algorithms (Tomtec™ and Dynamic Heart Model (DHM)) were used in 110 patients. Intra- and interobserver reproducibility and intervendor comparison were performed in additional patients’ subsets. Forty patients underwent cardiac magnetic resonance (CMR). Feasibility was 100% for Tomtec, 98.2% for DHM, and 72.8% for conventional 3DE. Tomtec volumes were higher than 3DE and DHM (p < 0.001). Reproducibility was better for DHM (intraobserver LA maximum volume (LAmax) ICC 0.99 (95% CI 1.0–0.99), LA minimum volume (LAmin) 0.98 (95% CI 0.95–0.99), LApreA 0.96 (95% CI 0.91–0.98); interobserver LAmax ICC 0.98 (95% CI 0.96–0.99), LAmin 0.99 (95% CI 0.99–1.00), and LApreA 0.97 (95% CI 0.94–0.99)). Intervendor comparison showed differences between left ventricle (LV) software adapted for LA (p < 0.001). Tomtec underestimated the least LA volumes compared to CMR. These findings emphasize that dedicated software should be used for LA assessment, for consistent clinical longitudinal follow-up and research.
Fine-Grained Recognition of Surface Targets with Limited Data
Authors: Guo Runze , Sun Bei , Qiu Xiaotian , Su Shaojing , Zuo Zhen , Wu Peng
Published: December 2020

Recognition of surface targets has a vital influence on the development of military and civilian applications such as maritime rescue patrols, illegal-vessel screening, and maritime operation monitoring. However, owing to the interference of visual similarity and environmental variations and the lack of high-quality datasets, accurate recognition of surface targets has always been a challenging task. In this paper, we introduce a multi-attention residual model based on deep learning methods, in which channel and spatial attention modules are applied for feature fusion. In addition, we use transfer learning to improve the feature expression capabilities of the model under conditions of limited data. A function based on metric learning is adopted to increase the distance between different classes. Finally, a dataset with eight types of surface targets is established. Comparative experiments on our self-built dataset show that the proposed method focuses more on discriminative regions, avoiding problems like gradient disappearance, and achieves better classification results than B-CNN, RA-CNN, MAMC, and MA-CNN, DFL-CNN.
Reduced-Complexity Multiple-Symbol Detection of O-QPSK Signals in Smart Metering Utility Networks
Authors: Shi Congyu , Zhang Gaoyuan , Li Haiqiong , Han Congzheng , Tang Jie , Wen Hong , Wang Longye , Wang Dan
Published: December 2020

In this work, an implementation-friendly multiple-symbol detection (MSD) scheme is proposed for the IEEE 802.15.4g offset quadrature phase shift keying (O-QPSK) receivers over the slow fading channel. The full MSD scheme presents better detection performance than the symbol-by-symbol detection (SBSD) scheme, yet its complexity increases exponentially as the observation window length increases. We introduce a simplified MSD scheme based on two powerful strategies. We first seek the optimal and suboptimal decisions in each symbol position with the standard SBSD procedure. Then, the aforementioned optimal and suboptimal decisions instead of all candidates are jointly searched with the standard MSD procedure. That is, only the most and second most reliable candidates in each symbol position are selected to participate in the final detection. The simulation results demonstrate that the new MSD scheme can achieve more encouraging energy gain than the SBSD scheme, while the high complexity of full MSD is also effectively reduced. A more legitimate compromise between detection performance and complexity is thus accomplished, which enables smart metering utility networks (SUN) nodes to achieve energy saving and maximum service life.
Reply to Comment by Alison A. Monaghan, David A.C. Manning, and Zoe K. Shipton on ‘Repurposing Hydrocarbon Wells for Geothermal Use in the UK: The Onshore Fields with the Greatest Potential, by Watson et al. (2020)’
Authors: Watson Sean , Falcone Gioia , Westaway Rob
Published: December 2020

Monaghan, Manning, and Shipton [...]
Analysis of Thermal Parameters of Hemp Fiber Insulation
Authors: Gaujena Baiba , Agapovs Vladislavs , Borodinecs Anatolijs , Strelets Ksenia
Published: December 2020

Nowadays, sustainable construction is a key factor for reaching net-zero emissions of carbon dioxide all over the world. This goal is impossible to achieve by merely reducing the energy consumption of end-users. A more holistic approach should be taken, adopting sustainable industrial practices that use environmentally friendly materials on a large scale. This paper presents the analysis of the hydrothermal properties of hemp thermal insulation plates. We carried out extensive measurements and the analysis of the thermal conductivity coefficient, drying-out dynamics, and water absorption. The study was performed with experimental insulation samples based on the fiber obtained from hemp stems, prepared using different adhesive powders. The dimensions of the analyzed samples were 300 × 300 mm. The proposed samples are not yet available in mass production. Hemp does not flower in the Baltic region and was traditionally used for soil regeneration. Thus, using this raw material increases the added value of agricultural residues. Three series of hemp fiber samples with different substances and pressing modes were evaluated in the study. Each set of samples consisted of four plates with varying thicknesses and two different densities: 200 kg/m3 and 300 kg/m3. All samples exhibited a significant increase in moisture absorption and a strong correlation with the increase in thermal conductivity. The average thermal conductivity of the test samples ranged from 0.0544 to 0.0594 W/mK. The impact of the adhesive powder on the thermal conductivity was found to be extremely small. However, the values obtained were much higher than those for traditional thermal insulation materials, allowing to utilize the local agriculture residues and providing material for the construction of eco-friendly buildings.
Stimulation of Lipid Extraction Efficiency from Sewage Sludge for Biodiesel Production through Hydrothermal Pretreatment
Authors: Lee Jongkeun , Choi Oh Kyung , Oh Dooyoung , Lee Kawnyong , Park Ki Young , Kim Daegi
Published: December 2020

In this study, two types of sewage sludge (primary sludge and waste activated sludge) were hydrothermally treated at 125–250 °C to enhance the lipid extraction efficiency and obtain a higher biodiesel yield. The enhanced efficiency of the lipid extraction method was compared with the efficiency of the organic solvent extraction method. The results confirmed that a hydrothermal reaction could be an appropriate option for disrupting sludge cell walls and increasing the lipid extraction from sewage sludge. The highest lipid recovery efficiency was observed at 200 °C, and the lipid recovery efficiency of primary sludge and waste activated sludge increased from 7.56% and 5.35% to 14.01% and 11.55% by weight, respectively. Furthermore, transesterified lipids, such as biodiesel from sewage sludge, mostly consist of C16 and C18 methyl esters, and have features similar to those of jatropha oil-based biodiesel. During the hydrothermal treatment, the carbon content in the sludge decreased as the carbon transformed into lipids and the lipids were extracted. The volatile matter and fixed carbon content in the solid residue decreased and increased, respectively, through chemical dehydration and decarboxylation reactions under hydrothermal reaction conditions.
Quantitative Limit State Assessment of a 3-Inch Carbon Steel Pipe Tee in a Nuclear Power Plant Using a Damage Index
Authors: Kim Sung-Wan , Yun Da-Woon , Chang Sung-Jin , Park Dong-Uk , Jeon Bub-Gyu
Published: December 2020

Seismic motions are likely to cause large displacements in nuclear power plants because the main mode of their piping systems is dominated by the low-frequency region. Additionally, large relative displacement may occur in the piping systems because their supports are installed in several places, and each support is subjected to different seismic motions. Therefore, to assess the seismic performance of a piping system, the relative displacement repeated by seismic motions must be considered. In this study, in-plane cyclic loading tests were conducted under various constant amplitudes using test specimens composed of SCH 40 3-inch pipes and a tee in the piping system of a nuclear power plant. Additionally, an attempt was made to quantitatively express the failure criteria using a damage index based on the dissipated energy that used the force–displacement and moment–deformation angle relationships. The failure mode was defined as the leakage caused by a through-wall crack, and the failure criteria were compared and analyzed using the damage index of Park and Ang and that of Banon. Additionally, the method of defining the yield point required to calculate the damage index was examined. It was confirmed that the failure criteria of the SCH 40 3-inch carbon steel pipe tee can be effectively expressed using the damage index.
Second Life Batteries Used in Energy Storage for Frequency Containment Reserve Service
Authors: Janota Lukáš , Králík Tomáš , Knápek Jaroslav
Published: December 2020

The new Li-ion battery systems used in electric vehicles have an average capacity of 50 kWh and are expected to be discarded when they reach approximately 80% of their initial capacity, because they are considered to no longer be sufficient for traction purposes. Based on the official national future development scenarios and subsequent mathematical modeling of the number of electric vehicles (EVs), up to 400 GWh of storage capacity in discharged batteries will be available on the EU market by 2035. Therefore, since the batteries still have a considerable capacity after the end of their first life, they could be used in many stationary applications during their second life, such as support for renewables, flexibility, energy arbitrage, peak shaving, etc. Due to the high output power achieved in a short time, one of the most promising applications of these batteries are ancillary services. The study assesses the economic efficiency of the used batteries and presents several main scenarios depending on the likely future development of the interconnected EU regulatory energy market. The final results indicate that the best results of second-life batteries utilization lie in the provision of Frequency Containment Reserve Service, both from a technical and economic point of view. The internal rate of return fluctuates from 8% to 21% in the realistic scenario, and it supports the idea that such systems might be able to be in operation without any direct financial subsidies.
Study on Asymmetry Concentration of Mixed Oil in Products Pipeline
Authors: Wang Yi , Wang Baoying , Liu Yang , Liang Yongtu
Published: December 2020

Long-distance pipelines transporting multiple product oils such as gasoline, diesel and jet fuel, are important facilities for transporting fossil energy. One major concern in operation is the energy consumption of the pipeline. Energy consumption should be made optimized tracking batches of oils and cutting mixed oil, which requires an accurate prediction of concentration curve. In engineering, the concentration curve is usually assumed to be symmetric, but it is actually asymmetric, which may lead to estimation errors. Thus, the asymmetric concentration of mixed oil should be studied. The formation mechanism of the asymmetry of concentration curve has not been clearly clarified. A new method is proposed to measure the asymmetry of the concentration curve. Quantitative analysis is carried out for each factor on the asymmetry distribution of concentration curve. Based on the convection–diffusion equation, a modified oil-mixing model considering near wall adsorption effect is established. The model shows a good agreement with the Jablonski empirical formula. The error, compared with the experimental results, is less than 5%. The main findings are: (1) deviation volume has a negative correlation with pipe diameter and mean velocity; (2) adsorption coefficient has a greater impact on the length ratio of front and tail oil than diffusion coefficient; (3) the influence of all factors considered on the total length of mixed oil, front oil, tail oil and trail oil are basically the same; (4) if the limit of adsorption concentration in adsorption layer is 1, the reasonable value of adsorption coefficient a and b should be around 0.4. The results reveal the mechanism of asymmetric concentration of product oils and can provide practical suggestions to deal with the mixed oil.
A Data-Driven Approach to Extend Failure Analysis: A Framework Development and a Case Study on a Hydroelectric Power Plant
Authors: Antomarioni Sara , Bellinello Marjorie Maria , Bevilacqua Maurizio , Ciarapica Filippo Emanuele , da Silva Renan Favarão , de Souza Gilberto Francisco Martha
Published: December 2020

Power plants are required to supply the electric demand efficiently, and appropriate failure analysis is necessary for ensuring their reliability. This paper proposes a framework to extend the failure analysis: indeed, the outcomes traditionally carried out through techniques such as the Failure Mode and Effects Analysis (FMEA) are elaborated through data-driven methods. In detail, the Association Rule Mining (ARM) is applied in order to define the relationships among failure modes and related characteristics that are likely to occur concurrently. The Social Network Analysis (SNA) is then used to represent and analyze these relationships. The main novelty of this work is represented by support in the maintenance management process based not only on the traditional failure analysis but also on a data-driven approach. Moreover, the visual representation of the results provides valuable support in terms of comprehension of the context to implement appropriate actions. The proposed approach is applied to the case study of a hydroelectric power plant, using real-life data.
Following the Roman Army between the Southern Foothills of the Cantabrian Mountains and the Northern Plains of Castile and León (North of Spain): Archaeological Applications of Remote Sensing and Geospatial Tools
Authors: Menéndez Blanco Andrés , García Sánchez Jesús , Costa-García José Manuel , Fonte João , González-Álvarez David , Vicente García Víctor
Published: December 2020

Sixty-six new archaeological sites have been discovered thanks to the combined use of different remote sensing techniques and open access geospatial datasets (mainly aerial photography, satellite imagery, and airborne LiDAR). These sites enhance the footprint of the Roman military presence in the northern fringe of the River Duero basin (León, Palencia, Burgos and Cantabria provinces, Spain). This paper provides a detailed morphological description of 66 Roman military camps in northwestern Iberia that date to the late Republic or early Imperial eras. We discuss the different spatial datasets and GIS tools used for different geographic contexts of varied terrain and vegetation. Finally, it stresses out the relevance of these novel data to delve into the rationale behind the Roman army movements between the northern Duero valley and the southern foothills of the Cantabrian Mountains. We conclude that methodological approaches stimulated by open-access geospatial datasets and enriched by geoscientific techniques are fundamental to understand the expansion of the Roman state in northwestern Iberia during the 1st c. BC properly. This renewed context set up a challenging scenario to overcome traditional archaeological perspectives still influenced by the cultural-historical paradigm and the pre-eminence of classical written sources.
Serum Gamma Glutamyltransferase Is Associated with 25-Hydroxyvitamin D Status in Elderly Patients with Stable Coronary Artery Disease
Authors: Danikiewicz Aleksander , Hudzik Bartosz , Nowak Justyna , Kowalska Joanna , Zieleń-Zynek Iwona , Szkodzinski Janusz , Naung Tun Han , Zubelewicz-Szkodzinska Barbara
Published: December 2020

Background: No previous study has investigated the association between gamma glutamyltransferase (GGT) and vitamin D in patients with stable coronary artery disease (CAD). We investigated the cross-sectional associations between vitamin D status as assessed by serum 25(OH)D and GGT. Methods: 169 patients were enrolled. Study population was divided into three groups: 1: 25(OH)D < 10 ng/mL (n = 59); 2: 25(OH)D 10–20 ng/mL (n = 82), and 3: 25(OH)D > 20 ng/mL (n = 28). Based on a cut-off GGT value identified in ROC analysis, we also divided the study population to compare the following groups: GGT ≤19 (n = 66) and GGT >19 (n = 103). Results: GGT activity was the highest in vitamin D severely deficient patients and the lowest in vitamin D insufficient patients. GGT was inversely correlated with 25(OH)D concentrations (R = −0.23; p = 0.002). The receiver operating characteristics curve identified the discrimination threshold of GGT of >19 U/L in predicting vitamin D deficiency. Higher leukocyte and neutrophil counts and lower 25(OH)D concentration were found in patients with GGT > 19 U/L. Conclusions: We identified an interaction between declining 25(OH)D levels and rising GGT levels with increasing age, which resulted in an unfavorable 25(OH)D-to-GGT ratio in stable CAD patients. These results suggest that these changes might further contribute to a high cardiovascular risk in the elderly.
The Effect of Balance and Sand Training on Postural Control in Elite Beach Volleyball Players
Authors: Sebastia-Amat Sergio , Ardigò Luca Paolo , Jimenez-Olmedo Jose Manuel , Pueo Basilio , Penichet-Tomas Alfonso
Published: December 2020

The aim of this work was to evaluate the effectiveness of a 12-week-long balance training program on the postural control of elite male beach volleyball players and the effect on balance when swapping to specific sports training in the sand in the following 12 weeks. Six elite players were tested before and after the balance training program and also 12 weeks after the balance training had finished. To this aim, a pressure platform was used to collect the following center of pressure parameters: path length, speed, mean position, and root-mean-square amplitude in the medial-lateral and anteroposterior planes. Romberg quotients for the center of pressure parameters were also calculated. The results of the present study showed better static postural control after specific balance training: smaller path length and speed under open eyes condition in dominant (p = 0.015; p = 0.009, respectively) and non-dominant monopedal stances (p = 0.005; p = 0.004, respectively). Contrastingly, 12 weeks after the balance training program, the path length and speed values under open eyes condition in bipedal stance increased significantly (p = 0.045; p = 0.004, respectively) for sand training. According to our results, balance training is effective to achieve positive balance test scores. It is speculated, and yet to be proven, that sand training could be effective to improve dynamic and open eyes postural control during beach volleyball practice. In beach volleyball players, a balance training program is effective to develop static balance but the effect of ecological sand training on dynamic performance deserves specific investigation.
Relationship between Land Use/Land-Use Change and Human Health in Australia: A Scoping Study
Authors: Davey Tamzyn M , Selvey Linda A
Published: December 2020

We undertook a scoping study to map the relevant evidence, summarise the findings, and to help identify gaps in the knowledge base on the relationship between land use/land-use change and human health in Australia. Our systematic search of the scientific literature for relevant articles up to August 2020 identified 37 articles. All 37 articles meeting our inclusion criteria were published after 2003. Zoonotic or vector-borne disease constituted the most common health outcome type studied. Agriculture/grazing was the land use/land-use change type most frequently represented in the literature, followed by coal seam gas extraction and open cut coal mining. The relationship between land use/land use change and human health in Australia, is not conclusive from the existing evidence. This is because of (1) a lack of comprehensive coverage of the topic, (2) a lack of coverage of the geography, (3) a lack of coverage of study types, and (4) conflicting results in the research already undertaken. If we are to protect human health and the ecosystems which support life, more high-quality, specific, end-user driven research is needed to support land management decisions in Australia. Until the health effects of further land use change are better known and understood, caution ought to be practiced in land management and land conversion.
Self-Declared Roma Ethnicity and Health Insurance Expenditures: A Nationwide Cross-Sectional Investigation at the General Medical Practice Level in Hungary
Authors: Kasabji Feras , Alrajo Alaa , Vincze Ferenc , Kőrösi László , Ádány Róza , Sándor János
Published: December 2020

The inevitable rising costs of health care and the accompanying risk of increasing inequalities raise concerns. In order to make tailored policies and interventions that can reduce this risk, it is necessary to investigate whether vulnerable groups (such as Roma, the largest ethnic minority in Europe) are being left out of access to medical advances. Objectives: The study aimed to describe the association between general medical practice (GMP) level of average per capita expenditure of the National Health Insurance Fund (NHIF), and the proportion of Roma people receiving GMP in Hungary, controlled for other socioeconomic and structural factors. Methods: A cross-sectional study that included all GMPs providing care for adults in Hungary (N = 4818) was conducted for the period 2012–2016. GMP specific data on health expenditures and structural indicators (GMP list size, providing care for adults only or children also, type and geographical location of settlement, age of GP, vacancy) for secondary analysis were obtained from the NHIF. Data for the socioeconomic variables were from the last census. Age and sex standardized specific socioeconomic status indicators (standardized relative education, srEDU; standardized relative employment, srEMP; relative housing density, rHD; relative Roma proportion based on self-reported data, rRP) and average per capita health expenditure (standardized relative health expenditure, srEXP) were computed. Multivariate linear regression model was applied to evaluate the relationship of socioeconomic and structural indicators with srEXP. Results: The srEDU had significant positive (b = 0.199, 95% CI: 0.128; 0.271) and the srEMP had significant negative (b = −0.282, 95% CI: −0.359; −0.204) effect on srEXP. GP age > 65 (b = −0.026, 95% CI: −0.036; −0.016), list size <800 (b = −0.043, 95% CI: −0.066; −0.020) and 800–1200 (b = −0.018, 95% CI: −0.031; −0.004]), had significant negative association with srEXP, and GMP providing adults only (b = 0.016, 95% CI: 0.001;0.032) had a positive effect. There was also significant expenditure variability across counties. However, rRP proved not to be a significant influencing factor (b = 0.002, 95% CI: −0.001; 0.005). Conclusion: As was expected, lower education, employment, and small practice size were associated with lower NHIF expenditures in Hungary, while the share of self-reported Roma did not significantly affect health expenditures according to our GMP level study. These findings do not suggest the necessity for Roma specific indicators elaborating health policy to control for the risk of widening inequalities imposed by rising health expenses.
The Academic Collaborative Center Older Adults: A Description of Co-Creation between Science, Care Practice and Education with the Aim to Contribute to Person-Centered Care for Older Adults
Authors: Luijkx Katrien , van Boekel Leonieke , Janssen Meriam , Verbiest Marjolein , Stoop Annerieke
Published: December 2020

Long-term care for older adults is in transition. Organizations offering long-term care for older adults are expected to provide person-centered care (PCC) in a complex context, with older adults aging in place and participating in society for as long as possible, staff shortages and the slow adoption of technological solutions. To address these challenges, these organizations increasingly use scientific knowledge to evaluate and innovate long-term care. This paper describes how co-creation, in the sense of close, intensive, and equivalent collaboration between science, care practice, and education, is a key factor in the success of improving long-term care for older adults. Such co-creation is central in the Academic Collaborative Center (ACC) Older Adults of Tilburg University. In this ACC, Tilburg University has joined forces with ten organizations that provide care for older adults and CZ zorgkantoor to create both scientific knowledge and societal impact in order to improve the quality of person-centered care for older adults. In the Netherlands, a “zorgkantoor” arranges long-term (residential) care on behalf of the national government. A zorgkantoor makes agreements on cost and quality with care providers and helps people that are in need of care to decide what the best possible option in their situation is. The CZ zorgkantoor arranges the long-term (residential) care in the south and southwest of the Netherlands. This paper describes how we create scientific knowledge to contribute to the knowledge base of PCC for older adults by conducting social scientific research in which the perspectives of older adults are central. Subsequently, we show how we create societal impact by facilitating and stimulating the use of our scientific knowledge in daily care practice. In the closing section, our ambitions for the future are discussed.
The Association of Different Types of Leisure Time Physical Activities with Cardiometabolic Outcomes in Singapore—Findings from the Multi-Ethnic Cohort Study
Authors: Müller-Riemenschneider Falk , Hong Yueheng , Tan Kristin Hui Xian , van Dam Rob M. , Uijtdewilligen Léonie
Published: December 2020

The study aimed to investigate the association between leisure time physical activity (LTPA) subtypes and cardiometabolic outcomes in the Singapore Multi-Ethnic Cohort (MEC). Self-reported data on socio-demographics, lifestyle factors, LTPA subtypes, and health screening data on body-mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP), triglycerides (TG), and HDL-and LDL cholesterol were collected. Multivariable linear regression analyses were used adjusting for confounders. The mean age of 9768 participants was 45.2 ± 12.5 years (57.3% female, 47.3% Chinese, 26.0% Malay, and 26.8% Indians). Overall, 65.8% engaged in LTPA, and walking, strength/fitness and running were most common. Higher total LTPA was associated with lower WC, DBP, TG, a trend towards lower BMI, and higher SBP and HDL. Running was beneficially associated with all outcomes except for SBP and LDL. Balance exercises (BMI, SBP and DBP), cycling (BMI, WC and HDL), and strength/fitness (BMI, WC, TG and HDL) were also favorably associated with a number of outcomes, whereas ball games (DBP and TG), dancing (HDL) and other LTPA (DBP) were only favorably associated with selected outcomes. Unfavorable associations were found for total LTPA (SBP), strength/fitness (SBP), golf (DBP) and swimming (BMI and WC). Further research is warranted to inform future health promotion efforts.
The Palladium(II) Complex of Aβ4−16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids
Authors: Mital Mariusz , Szutkowski Kosma , Bossak-Ahmad Karolina , Skrobecki Piotr , Drew Simon C. , Poznański Jarosław , Zhukov Igor , Frączyk Tomasz , Bal Wojciech
Published: December 2020

The Aβ4−42 peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer’s Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in Aβ4−16 and Aβ4−9 model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage. Structural characterization of Cu(II)Aβ4−x complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-Aβ4−16 complex as a model. To avoid a kinetic trapping of Pd(II) in an inappropriate transient structure, we designed an appropriate pH-dependent synthetic procedure for ATCUN Pd(II)Aβ4−16, controlled by CD, fluorescence and ESI-MS. Its assignments and structure at pH 6.5 were obtained by TOCSY, NOESY, ROESY, 1H-13C HSQC and 1H-15N HSQC NMR experiments, for natural abundance 13C and 15N isotopes, aided by corresponding experiments for Pd(II)-Phe-Arg-His. The square-planar Pd(II)-ATCUN coordination was confirmed, with the rest of the peptide mostly unstructured. The diffusion rates of Aβ4−16, Pd(II)-Aβ4−16 and their mixture determined using PGSE-NMR experiment suggested that the Pd(II) complex forms a supramolecular assembly with the apopeptide. These results confirm that Pd(II) substitution enables NMR studies of structural aspects of Cu(II)-Aβ complexes.
Cleaning Teeth Reduces the Inflammatory Response of Macrophages to Acid Dentine Lysate
Authors: Nasirzade Jila , Kargarpour Zahra , Panahipour Layla , Schwarz Frank , Gruber Reinhard
Published: December 2020

Particulate autogenous tooth roots are used for alveolar bone augmentation surgery; however, dental plaque may provoke an inflammatory response that may counteract the desired graft consolidation process. Traditional mechanical cleaning of extracted teeth may be of support to lower a possible inflammatory response of the autograft. To test this assumption, extracted porcine teeth were left either uncleaned or underwent mechanical cleaning with a toothbrush and toothpaste before being fragmented and subjected to acid lysis, termed as unclean acid dentine lysate (ucADL) and clean acid dentine lysate (cADL), respectively. The inflammatory responses of murine macrophage RAW 264.7 cells being exposed to the respective acid dentine lysates were evaluated at the level of inflammatory gene expression and IL6 immunoassays. We report here that acid lysates obtained from uncleaned teeth provoked a robust increase in IL1β, IL6, and COX2 in RAW 264.7 cells. The mechanical removal of dental plaque significantly reduced the inflammatory response. Consistently, Limulus tests revealed that tooth cleaning lowers the presence of endotoxins in dentine lysates. To further prove the involvement of endotoxins, a toll-like receptor 4 (TLR4) inhibitor TAK242 was introduced. TAK242 abolished the inflammatory response provoked by acid lysates obtained from uncleaned teeth in RAW 264.7 cells. Moreover, nuclear translocation and phosphorylation of the TLR4 downstream NFκB-p65 were attenuated at the presence of cleaned versus uncleaned dentine lysates. Taken together, our data support the importance of dental plaque removal of teeth being extracted for alveolar bone augmentation surgery.
Transcriptomic Leaf Profiling Reveals Differential Responses of the Two Most Traded Coffee Species to Elevated [CO2]
Authors: Marques Isabel , Fernandes Isabel , David Pedro H.C. , Paulo Octávio S. , Goulao Luis F. , Fortunato Ana S. , Lidon Fernando C. , DaMatta Fábio M. , Ramalho José C. , Ribeiro-Barros Ana I.
Published: December 2020

As atmospheric [CO2] continues to rise to unprecedented levels, understanding its impact on plants is imperative to improve crop performance and sustainability under future climate conditions. In this context, transcriptional changes promoted by elevated CO2 (eCO2) were studied in genotypes from the two major traded coffee species: the allopolyploid Coffea arabica (Icatu) and its diploid parent, C. canephora (CL153). While Icatu expressed more genes than CL153, a higher number of differentially expressed genes were found in CL153 as a response to eCO2. Although many genes were found to be commonly expressed by the two genotypes under eCO2, unique genes and pathways differed between them, with CL153 showing more enriched GO terms and metabolic pathways than Icatu. Divergent functional categories and significantly enriched pathways were found in these genotypes, which altogether supports contrasting responses to eCO2. A considerable number of genes linked to coffee physiological and biochemical responses were found to be affected by eCO2 with the significant upregulation of photosynthetic, antioxidant, and lipidic genes. This supports the absence of photosynthesis down-regulation and, therefore, the maintenance of increased photosynthetic potential promoted by eCO2 in these coffee genotypes.
On the Single-Crystal Structure of Tenofovir Alafenamide Mono-Fumarate: A Metastable Phase Featuring a Mixture of Co-Crystal and Salt
Authors: Wang Jian-Wei , Liu Lu , Yu Ka-Xi , Bai Hong-Zhen , Zhou Jun , Zhang Wen-Hua , Hu Xiurong , Tang Guping
Published: December 2020

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya® for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy® for the treatment of chronic hepatitis B. Vemlidy® is also a monotherapeutic regimen formulated as TAF hemifumarate (1; TAF:fumarate = 2:1). In this work, we report for the first time the single-crystal structure of TAF fumarate hemihydrate (2, TAF:fumarate:H2O = 2:2:1). Compound 2 is initially documented as a salt in which one proton of the fumaric acid migrates to the amine group of the adenine moiety in TAF. It was recently proposed that ca. 20–30% proton is transferred to the N atom on the aromatic adenine backbone. We herein provide definitive single-crystal X-ray diffraction results to confirm that 2, though phase pure, is formed as a mixture of co-crystal (75%) and salt (25%). It features two pairs of TAF fumarates, wherein one of the four H atoms on the fumaric acid is transferred to the N atom of the adjacent adenine moiety while the other three carboxylates remain in their intrinsic acid form. Compound 2 is a metastable phase during the preparation of 1 and can be isolated by halting the reaction during the refluxing of TAF and fumaric acid in acetonitrile (MeCN). Our report complements the previous characterizations of TAF monofumarate, and its elusive structural patterns are finally deciphered.
Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension
Authors: Gerthoffer William
Published: December 2020

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.
Autonomous and Assisted Control for Synthetic Microbiology
Authors: Banderas Alvaro , Le Bec Matthias , Cordier Céline , Hersen Pascal
Published: December 2020

The control of microbes and microbial consortia to achieve specific functions requires synthetic circuits that can reliably cope with internal and external perturbations. Circuits that naturally evolved to regulate biological functions are frequently robust to alterations in their parameters. As the complexity of synthetic circuits increases, synthetic biologists need to implement such robust control “by design”. This is especially true for intercellular signaling circuits for synthetic consortia, where robustness is highly desirable, but its mechanisms remain unclear. Cybergenetics, the interface between synthetic biology and control theory, offers two approaches to this challenge: external (computer-aided) and internal (autonomous) control. Here, we review natural and synthetic microbial systems with robustness, and outline experimental approaches to implement such robust control in microbial consortia through population-level cybergenetics. We propose that harnessing natural intercellular circuit topologies with robust evolved functions can help to achieve similar robust control in synthetic intercellular circuits. A “hybrid biology” approach, where robust synthetic microbes interact with natural consortia and—additionally—with external computers, could become a useful tool for health and environmental applications.
Description of a Novel Mechanism Possibly Explaining the Antiproliferative Properties of Glucocorticoids in Duchenne Muscular Dystrophy Fibroblasts Based on Glucocorticoid Receptor GR and NFAT5
Authors: Herbelet Sandrine , De Paepe Boel , De Bleecker Jan L.
Published: December 2020

Glucocorticoids are drugs of choice in Duchenne muscular dystrophy (DMD), prolonging patients’ ambulation. Their mode of action at the protein level is not completely understood. In DMD, muscle tissue is replaced by fibrotic tissue produced by fibroblasts, reducing mobility. Nuclear factor of activated T-cells 5 (NFAT5) is involved in fibroblast proliferation. By treating one DMD fibroblast cell culture and one of unaffected skeletal muscle fibroblasts with methylprednisolone (MP) or hydrocortisone (HC) for 24 h or 12 d, the antiproliferative properties of glucocorticoids could be unraveled. NFAT5 localization and expression was explored by immunocytochemistry (ICC), Western blotting (WB) and RT-qPCR. NFAT5 and glucocorticoid receptor (GR) colocalization was measured by ImageJ. GR siRNA was used, evaluating GR’s influence on NFAT5 expression during MP and HC treatment. Cell proliferation was monitored by IncuCyte ZOOM. In DMD fibroblasts, treatment with MP for 24 h induced dots (ICC) positive for NFAT5 and colocalizing with GR. After 12 d of MP or HC in DMD fibroblasts, NFAT5 expression was decreased (RT-qPCR and WB) and growth arrest was observed (Incucyte ZOOM), whereas NFAT5 expression and cell growth remained unchanged in unaffected skeletal muscle fibroblasts. This study may help understand the antiproliferative properties of glucocorticoids in DMD fibroblasts.
Focus on DNA Glycosylases—A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets
Authors: Hans Fabienne , Senarisoy Muge , Bhaskar Naidu Chandini , Timmins Joanna
Published: December 2020

Cancer is the second leading cause of death with tens of millions of people diagnosed with cancer every year around the world. Most radio- and chemotherapies aim to eliminate cancer cells, notably by causing severe damage to the DNA. However, efficient repair of such damage represents a common mechanism of resistance to initially effective cytotoxic agents. Thus, development of new generation anticancer drugs that target DNA repair pathways, and more particularly the base excision repair (BER) pathway that is responsible for removal of damaged bases, is of growing interest. The BER pathway is initiated by a set of enzymes known as DNA glycosylases. Unlike several downstream BER enzymes, DNA glycosylases have so far received little attention and the development of specific inhibitors of these enzymes has been lagging. Yet, dysregulation of DNA glycosylases is also known to play a central role in numerous cancers and at different stages of the disease, and thus inhibiting DNA glycosylases is now considered a valid strategy to eliminate cancer cells. This review provides a detailed overview of the activities of DNA glycosylases in normal and cancer cells, their modes of regulation, and their potential as anticancer drug targets.
Endocrine-Disrupting Chemicals’ (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1
Authors: Buoso Erica , Masi Mirco , Racchi Marco , Corsini Emanuela
Published: December 2020

Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system. We provide an analysis of immunomodulatory and cancer-promoting effects of different EDCs in shaping tumour microenvironment, with a final focus on the scaffold protein RACK1 as a pivotal molecular player due to its dual role in immune and cancer contexts.
Glycosylation in Indolent, Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling
Authors: Gilgunn Sarah , Murphy Keefe , Stöckmann Henning , Conroy Paul J. , Murphy T. Brendan , Watson R. William , O’Kennedy Richard J. , Rudd Pauline M. , Saldova Radka
Published: December 2020

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.
Bacterial Metabolites of Human Gut Microbiota Correlating with Depression
Authors: Averina Olga V. , Zorkina Yana A. , Yunes Roman A. , Kovtun Alexey S. , Ushakova Valeriya M. , Morozova Anna Y. , Kostyuk George P. , Danilenko Valery N. , Chekhonin Vladimir P.
Published: December 2020

Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.