bluuebunny/crossref_metadata_2025 huggingface dataset:
Microvascular Imaging as a Novel Tool for the Assessment of Blood Flow Velocity in Patients with Systemic Sclerosis: A Single-Center Feasibility Study
Authors: Rademacher Jan-Gerd , Buschfort Rosa Marie , Asendorf Thomas , Korendovych Viktor , Tampe Björn , Korsten Peter
Published: February 2022

Systemic sclerosis is an autoimmune disease characterized by organ fibrosis and vasculopathy. Almost all patients suffer from Raynaud’s phenomenon. Nailfold video capillaroscopy is the most widely imaging technique available, but flow quantification is impossible. Therefore, novel imaging techniques are of interest. We performed a single-center feasibility study using Microvascular Imaging (MVI) for flow quantification of small fingertip vessels. We compared 20 healthy controls (HCs) with 20 systemic sclerosis (SSc) patients. In HCs, measurements were, on average, statistically significantly higher when combined for all fingers (median 10.68 vs. 6 cm/s, Δ = 4.68 cm/s, p < 0.0001) and for individual fingers. An optimal cut-off value of peak systolic (PS) velocity of <6.13 cm/s and end-diastolic (ED) velocity of <2.13 cm/s discriminated HCs from SSc. Test characteristics for PS showed excellent sensitivity (0.90, 95% CI 0.70–0.98) and specificity (0.85, 95% CI 0.64–0.95; LR + 6.0). For ED velocity, sensitivity was 0.85 (95% CI 0.64–0.95) and specificity was 0.80 (95% CI 0.58–0.92, LR + 4.25). Here, we present the first study on the use of MVI to assess blood flow in the fingertips with high sensitivity and specificity in SSc. Future studies are needed to investigate correlations with the risk of organ complications, such as digital ulcers or pulmonary arterial hypertension.
Modelling Automated Planning Problems for Teams of Mobile Manipulators in a Generic Industrial Scenario
Authors: Bezrucav Stefan-Octavian , Corves Burkhard
Published: February 2022

Flexible control strategies are required in industrial scenarios to coordinate the actions of mobile manipulators (e.g., robots and humans). Temporal planning approaches can be used as such control strategies because they can generate those actions for the agents that must be executed to reach the goals, from any given state of the world. To deploy such approaches, planning models must be formulated. Although available in the literature, these models are not generic enough such that they can be easily transferred to new use cases. In this work, a generic industrial scenario is derived from real scenarios. For this scenario, a generic planning problem is developed. To demonstrate their generality, the two constructs are configured for a new scenario, where custom grippers are assembled. Lastly, a validation methodology is developed for the generic planning problem. The results show that the generic industrial scenario and the generic planning problem can be easily instantiated for new use cases, without any new modelling. Further, the proposed validation methodology guarantees that these planning problems are complete enough to be used in industrial use cases. The generic scenario, the planning problems, and the validation methodology are proposed as standards for use when deploying temporal planning in industrial scenarios with mobile manipulators.
Investigation of a Solar-Driven Organic Rankine Cycle with Reheating
Authors: Bellos Evangelos , Lykas Panagiotis , Tzivanidis Christos
Published: February 2022

The purpose of this simulation study is the examination of a solar-driven power cycle that is driven by collectors with evacuated tubes. The power cycle is an organic Rankine cycle (ORC) that works with cyclopentane. The novelty of the cycle is the use of reheating in order to enhance its thermodynamic efficiency, while the cycle also has a recuperator. Moreover, the cycle is compared with the conventional ORC in order to determine the performance enhancement with the examined idea. The analysis is done with a developed program in Engineering Equation Solver and both in steady-state and transient conditions for a typical year. The analysis was conducted in terms of energy and economic performance. According to an optimization procedure for maximizing the net present values of the investment, it is found that the novel design leads to a net present value of 68 k€, a simple payback of 10 years, and a yearly energy efficiency of 7.0%, while the respective values for the conventional ORC are 44 k€, 10.8 years, and 5.1% for its optimal design according to the net present values maximization. Thus, it is obvious that the suggested design increases both energy and financial performance, compared to the usual design.
Recent Progress in Radon Metrology at IFIN-HH, Romania
Authors: Luca Aurelian , Rădulescu Ileana , Ioan Mihail-Răzvan , Fugaru Viorel , Teodorescu Constantin , Barna Cătălina , Tuță Cătălin Stelian , Tugulan Cornel Liviu , Antohe Andrei , Lalău Ioana , Cîmpeanu Cătălina , Postolache Cristian
Published: February 2022

The practical implementation of the European Council Directive no. 2013/59/EURATOM in Romania requires reliable indoor measurements of the radon (222Rn) activity concentration in air. In Romania, several Testing Laboratories were designated for radon activity and/or radon activity concentration in air measurements by the Romanian National Commission for Nuclear Activities Control (CNCAN). The calibration of the instruments used for indoor radon activity concentration measurements is very important. IFIN-HH, through its Ionizing Radiation Metrology Laboratory (LMRI), performed advanced research in the field of radon metrology, using radon standard sources prepared by LMRI, its radon chamber facility and a new reference radon monitor. The most recent results are described in this article. The radon chamber facility from IFIN-HH was technically improved, and new equipment and methods were set up and tested in order to provide new calibration services for customers. Additionally, calibration of the radon monitors was performed, as well as of the systems with solid-state nuclear track detectors, used for radon in air activity concentration measurements. IFIN-HH/LMRI obtained the CNCAN designation as Calibration Laboratory for installations measuring the radon activity concentration in air.
Evaluating Probability Distribution Functions for the Standardized Precipitation Evapotranspiration Index over Ethiopia
Authors: Yimer Estifanos Addisu , Van Schaeybroeck Bert , Van de Vyver Hans , van Griensven Ann
Published: February 2022

Drought indices are used to identify and monitor drought events. The standardized precipitation evapotranspiration index (SPEI) is a widely used index based on accumulated water balance. There is, however, no broad consensus on which probability distribution is the most appropriate for water balances. This issue is investigated for Ethiopia using 125 meteorological stations spread across the country. Based on long-term series, a selection was made among the generalized extreme value, Pearson type 3, and generalized logistics (Genlog) distributions. Additionally, the effect of using actual, instead of potential, evapotranspiration and a limited amount of data (10, 15, 20, and 25 years) is explored. Genlog is found to be the best distribution for all accumulation periods. Furthermore, there is a considerable difference amongst the SPEI values estimated from the three distributions on the identification of extreme wet or extreme dry periods. Next, there are significant differences between standardized precipitation actual evapotranspiration index (SPAEI) and SPEI, signifying the importance of drought index selection for proper drought monitoring. Finally, time series of 20 or 25 years of data lead to almost similar SPEI values to those estimated using more than 30 years of data, so could potentially be used to assess drought in Ethiopia.
Variation and Driving Factor of Aerosol Optical Depth over the South China Sea from 1980 to 2020
Authors: Sun Enwei , Fu Chuanbo , Yu Wei , Xie Ying , Lu Yiwen , Lu Chunsong
Published: February 2022

Spatial and temporal variation of aerosol optical depth (AOD) and optical depth of different aerosol types derived from the second Modern-Era Retrospective analysis for Research and Applications (MERRA-2) over the South China Sea (SCS) between 1980 and 2020 were studied. AOD distribution showed different characteristics throughout the entire SCS. Sulfate Aerosol Optical Depth (SO4AOD) and Sea Salt Aerosol Optical Depth (SSAOD) mainly contributed to the spatial and temporal variation of AOD over the SCS. A significant increasing trend followed by a decreasing trend of AOD could be observed in the north of the SCS from 1980 to 2020. Mean MERRA-2 AOD between 1980 and 2020 showed that AOD was high in the north and low in the south and that AOD gradually decreased from north to south over the SCS. AOD after 2000 was obviously higher than that of the 1980s and 1990s. Higher AOD appeared in the spring and winter, and low AOD appeared in the summer. The spatial distribution of scattering aerosol optical depth (SAOD) was similar to AOD distribution over the SCS. SO4AOD and SSAOD were obviously higher than black carbon aerosol optical depth (BCAOD), organic carbon aerosol optical depth (OCAOD), and dust aerosol optical depth (DUAOD) over the SCS. SO4AOD accounted for over 50% of total AOD (TAOD) over the north of the SCS, while BCAOD and DUAOD accounted for less than 10% of TAOD over the entire SCS. An obvious annual mean TAOD increase between 1980 and 2007 could be observed over the northern part of the SCS (NSCS), while a TAOD decrease happened from 2008 to 2020 in this region. The correlation coefficient between TAOD and SO4AOD over NSCS from 1980 to 2020 was about 0.93, indicating SO4AOD was the driving factor of TAOD variation in this area. Different AOD variation trends over the different areas of the SCS could be observed during the two periods including 1980–2007 and 2008–2020. AOD increase appeared over most of the SCS during the period from 1980 to 2007, while AOD decrease could be observed over most of the SCS from 2008 to 2020.
Generalized Beta Prime Distribution Applied to Finite Element Error Approximation
Authors: Chaskalovic Joël , Assous Franck
Published: February 2022

In this paper, we propose a new family of probability laws based on the Generalized Beta Prime distribution to evaluate the relative accuracy between two Lagrange finite elements Pk1 and Pk2,(k1<k2). Usually, the relative finite element accuracy is based on the comparison of the asymptotic speed of convergence, when the mesh size h goes to zero. The new probability laws we propose here highlight that there exists, depending on h, cases where the Pk1 finite element is more likely accurate than the Pk2 element. To confirm this assertion, we highlight, using numerical examples, the quality of the fit between the statistical frequencies and the corresponding probabilities, as determined by the probability law. This illustrates that, when h goes away from zero, a finite element Pk1 may produce more precise results than a finite element Pk2, since the probability of the event “Pk1is more accurate thanPk2” becomes greater than 0.5. In these cases, finite element Pk2 is more likely overqualified.
Gold-Modified Molecularly Imprinted N-Methacryloyl-(l)-phenylalanine-containing Electrodes for Electrochemical Detection of Dopamine
Authors: Abu Shama Nemah , Aşır Süleyman , Ozsoz Mehmet , Göktürk Ilgım , Türkmen Deniz , Yılmaz Fatma , Denizli Adil
Published: February 2022

A molecularly imprinted polymer-based pencil graphite electrode (MIP PGE) sensor, modified with gold nanoparticles, was utilized for the detection of dopamine in the presence of other biochemical compounds using cyclic voltammetry (CV) and differential pulse voltammetry (DPV), depending on its strong electroactivity function. The pulse voltammetry methods recorded the highest response. In addition to the high oxidation rate of DA and the other biomolecule interferences available in the sample matrix used, which cause overlapping voltammograms, we aimed to differentiate them in a highly sensitive limit of detection range. The calibration curves for DA were obtained using the CV and DPV over the concentration range of 0.395–3.96 nM in 0.1 M phosphate buffer solution (PBS) at pH 7.4 with a correlation coefficient of 0.996 and a detection limit of 0.193 nM. The electrochemical technique was employed to detect DA molecules quantitatively in human blood plasma selected as real samples without applying any pre-treatment processes. MIP electrodes proved their ability to detect DA with high selectivity, even with epinephrine and norepinephrine competitor molecules and interferences, such as ascorbic acid (AA). The high level of recognition achieved by molecularly imprinted polymers (MIPs) is essential for many biological and pharmaceutical studies.
Machine Learning for Shape Memory Graphene Nanoribbons and Applications in Biomedical Engineering
Authors: León Carlos , Melnik Roderick
Published: February 2022

Shape memory materials have been playing an important role in a wide range of bioengineering applications. At the same time, recent developments of graphene-based nanostructures, such as nanoribbons, have demonstrated that, due to the unique properties of graphene, they can manifest superior electronic, thermal, mechanical, and optical characteristics ideally suited for their potential usage for the next generation of diagnostic devices, drug delivery systems, and other biomedical applications. One of the most intriguing parts of these new developments lies in the fact that certain types of such graphene nanoribbons can exhibit shape memory effects. In this paper, we apply machine learning tools to build an interatomic potential from DFT calculations for highly ordered graphene oxide nanoribbons, a material that had demonstrated shape memory effects with a recovery strain up to 14.5% for 2D layers. The graphene oxide layer can shrink to a metastable phase with lower constant lattice through the application of an electric field, and returns to the initial phase through an external mechanical force. The deformation leads to an electronic rearrangement and induces magnetization around the oxygen atoms. DFT calculations show no magnetization for sufficiently narrow nanoribbons, while the machine learning model can predict the suppression of the metastable phase for the same narrower nanoribbons. We can improve the prediction accuracy by analyzing only the evolution of the metastable phase, where no magnetization is found according to DFT calculations. The model developed here allows also us to study the evolution of the phases for wider nanoribbons, that would be computationally inaccessible through a pure DFT approach. Moreover, we extend our analysis to realistic systems that include vacancies and boron or nitrogen impurities at the oxygen atomic positions. Finally, we provide a brief overview of the current and potential applications of the materials exhibiting shape memory effects in bioengineering and biomedical fields, focusing on data-driven approaches with machine learning interatomic potentials.
Rhizosphere Tripartite Interactions and PGPR-Mediated Metabolic Reprogramming towards ISR and Plant Priming: A Metabolomics Review
Authors: Mashabela Manamele D. , Piater Lizelle A. , Dubery Ian A. , Tugizimana Fidele , Mhlongo Msizi I.
Published: February 2022

Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms colonising the rhizosphere. PGPR are involved in plant growth promotion and plant priming against biotic and abiotic stresses. Plant–microbe interactions occur through chemical communications in the rhizosphere and a tripartite interaction mechanism between plants, pathogenic microbes and plant-beneficial microbes has been defined. However, comprehensive information on the rhizosphere communications between plants and microbes, the tripartite interactions and the biochemical implications of these interactions on the plant metabolome is minimal and not yet widely available nor well understood. Furthermore, the mechanistic nature of PGPR effects on induced systemic resistance (ISR) and priming in plants at the molecular and metabolic levels is yet to be fully elucidated. As such, research investigating chemical communication in the rhizosphere is currently underway. Over the past decades, metabolomics approaches have been extensively used in describing the detailed metabolome of organisms and have allowed the understanding of metabolic reprogramming in plants due to tripartite interactions. Here, we review communication systems between plants and microorganisms in the rhizosphere that lead to plant growth stimulation and priming/induced resistance and the applications of metabolomics in understanding these complex tripartite interactions.
Responses of Fine Roots at Different Soil Depths to Different Thinning Intensities in a Secondary Forest in the Qinling Mountains, China
Authors: Pang Yue , Tian Jing , Yang Hang , Zhang Kai , Wang Dexiang
Published: February 2022

Fine roots make critical contributions to carbon stocks and terrestrial productivity, and fine roots with different diameters exhibit functional heterogeneity. However, the changed characteristics of fine roots with different diameters at different soil depths following thinning disturbances are poorly understood. We investigated the biomass, production, mortality and turnover rate of <0.5 mm, 0.5–1 mm, and 1–2 mm fine roots at 0–20 cm, 20–40 cm, and 40–60 cm soil depths under five thinning intensities (0%, 15%, 30%, 45%, and 60%) in a secondary forest in the Qinling Mountains. The biomass, production and turnover rate of <0.5 mm fine roots fluctuated with increasing thinning intensities, while the 0.5–1 mm and 1–2 mm fine-root biomass significantly decreased. The thinning intensities had no effects on the fine-root necromass or mortality. The change in the fine-root characteristics in deeper soils was more sensitive to the thinning intensities. The principal component analysis results showed that increased <0.5 mm fine-root biomass and production resulted from increased shrub and herb diversity and biomass and decreased soil nutrient availability, stand volume, and litter biomass, whereas the 0.5–1 mm and 1–2 mm fine-root biomass showed the opposite trends and changes. Our results suggest that different thinning intensities exhibit varied influential mechanisms on the changed characteristics of fine roots with different diameters.
Cytochromes P450 of Caenorhabditis elegans: Implication in Biological Functions and Metabolism of Xenobiotics
Authors: Larigot Lucie , Mansuy Daniel , Borowski Ilona , Coumoul Xavier , Dairou Julien
Published: February 2022

Caenorhabditis elegans is an important model used for many aspects of biological research. Its genome contains 76 genes coding for cytochromes P450 (P450s), and few data about the biochemical properties of those P450s have been published so far. However, an increasing number of articles have appeared on their involvement in the metabolism of xenobiotics and endobiotics such as fatty acid derivatives and steroids. Moreover, the implication of some P450s in various biological functions of C. elegans, such as survival, dauer formation, life span, fat content, or lipid metabolism, without mention of the precise reaction catalyzed by those P450s, has been reported in several articles. This review presents the state of our knowledge about C. elegans P450s.
The Role of Anti-Viral Effector Molecules in Mollusc Hemolymph
Authors: Watson Angus , Agius Jacinta , Ackerly Danielle , Beddoe Travis , Helbig Karla
Published: February 2022

Molluscs are major contributors to the international and Australian aquaculture industries, however, their immune systems remain poorly understood due to limited access to draft genomes and evidence of divergences from model organisms. As invertebrates, molluscs lack adaptive immune systems or ‘memory’, and rely solely on innate immunity for antimicrobial defence. Hemolymph, the circulatory fluid of invertebrates, contains hemocytes which secrete effector molecules with immune regulatory functions. Interactions between mollusc effector molecules and bacterial and fungal pathogens have been well documented, however, there is limited knowledge of their roles against viruses, which cause high mortality and significant production losses in these species. Of the major effector molecules, only the direct acting protein dicer-2 and the antimicrobial peptides (AMPs) hemocyanin and myticin-C have shown antiviral activity. A better understanding of these effector molecules may allow for the manipulation of mollusc proteomes to enhance antiviral and overall antimicrobial defence to prevent future outbreaks and minimize economic outbreaks. Moreover, effector molecule research may yield the description and production of novel antimicrobial treatments for a broad host range of animal species.
Utility of the Specialized Pro-Resolving Mediators as Diagnostic and Prognostic Biomarkers in Disease
Authors: Dalli Jesmond , Gomez Esteban Alberto , Jouvene Charlotte Camille
Published: February 2022

A precision medicine approach is widely acknowledged to yield more effective therapeutic strategies in the treatment of patients with chronic inflammatory conditions than the prescriptive paradigm currently utilized in the management and treatment of these patients. This is because such an approach will take into consideration relevant factors including the likelihood that a patient will respond to given therapeutics based on their disease phenotype. Unfortunately, the application of this precision medicine paradigm in the daily treatment of patients has been greatly hampered by the lack of robust biomarkers, in particular biomarkers for determining early treatment responsiveness. Lipid mediators are central in the regulation of host immune responses during both the initiation and resolution of inflammation. Amongst lipid mediators, the specialized pro-resolving mediators (SPM) govern immune cells to promote the resolution of inflammation. These autacoids are produced via the stereoselective conversion of essential fatty acids to yield molecules that are dynamically regulated during inflammation and exert potent immunoregulatory activities. Furthermore, there is an increasing appreciation for the role that these mediators play in conveying the biological actions of several anti-inflammatory therapeutics, including statins and aspirin. Identification and quantitation of these mediators has traditionally been achieved using hyphenated mass spectrometric techniques, primarily liquid-chromatography tandem mass spectrometry. Recent advances in the field of chromatography and mass spectrometry have increased both the robustness and the sensitivity of this approach and its potential deployment for routine clinical diagnostics. In the present review, we explore the evidence supporting a role for specific SPM as potential biomarkers for patient stratification in distinct disease settings together with methodologies employed in the identification and quantitation of these autacoids.
Correlation of Serum Acylcarnitines with Clinical Presentation and Severity of Coronary Artery Disease
Authors: Deda Olga , Panteris Eleftherios , Meikopoulos Thomas , Begou Olga , Mouskeftara Thomai , Karagiannidis Efstratios , Papazoglou Andreas S. , Sianos Georgios , Theodoridis Georgios , Gika Helen
Published: February 2022

Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and <0.001, respectively). Among CAD subgroups, median C5 levels were significantly decreased in unstable angina compared to STEMI (p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p < 0.001, respectively). Moreover, median C2, C3, C4 and C8 levels were significantly elevated in patients with diabetes mellitus (p < 0.001, <0.001, 0.029 and 0.011, respectively). Moreover, short-chain acylcarnitine C2, C4, C5 and C6 levels were elevated in patients with heavier calcification and lower left ventricular ejection fraction (LVEF) % (all p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.
The Class I HDAC Inhibitor Valproic Acid Strongly Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Immune System Activation
Authors: Blaauboer Amber , van Koetsveld Peter M. , Mustafa Dana A. M. , Dumas Jasper , Dogan Fadime , van Zwienen Suzanne , van Eijck Casper H. J. , Hofland Leo J.
Published: February 2022

Background: Gemcitabine efficacy in pancreatic cancer is often impaired due to limited intracellular uptake and metabolic activation. Epi-drugs target gene expression patterns and represent a promising approach to reverse chemoresistance. In this study, we investigate the chemosensitizing effect of different epi-drugs when combined with gemcitabine in pancreatic cancer. Methods: Mouse KPC3 cells were used for all experiments. Five different epi-drugs were selected for combination therapy: 5-aza-2′-deoxycytidine, hydralazine, mocetinostat, panobinostat, and valproic acid (VPA). Treatment effects were determined by cell proliferation and colony forming assays. Expression of genes were assessed by real-time quantitative PCR. The most promising epi-drug for combination therapy was studied in immune competent mice. Intratumor changes were defined using NanoString PanCancer panel IO360. Results: All epi-drugs, except hydralazine, potentiated the gemcitabine response in KPC3 cells (range decrease IC50 value 1.7–2-fold; p < 0.001). On colony formation, the cytotoxic effect of 0.5 ng/mL gemcitabine was 1.4 to 6.3 times stronger (p < 0.01). Two out of three drug-transporter genes were strongly upregulated following epi-drug treatment (a range fold increase of 17–124 and 9–60 for Slc28a1 and Slc28a3, respectively; all p < 0.001). VPA combined with gemcitabine significantly reduced tumor size with 74% compared to vehicle-treated mice and upregulated expression of immune-related pathways (range pathway score 0.86–1.3). Conclusions: These results provide a strong rationale for combining gemcitabine with VPA treatment. For the first time, we present intratumor changes and show activation of the immune system. Clinical trials are warranted to assess efficacy and safety of this novel combination in pancreatic cancer patients.
The Role of Gut–Liver Axis in Gut Microbiome Dysbiosis Associated NAFLD and NAFLD-HCC
Authors: Song Qian , Zhang Xiang
Published: February 2022

Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most prevalent chronic liver diseases worldwide due to the rapidly rising prevalence of obesity and metabolic syndrome. As a hepatic manifestation of metabolic disease, NAFLD begins with hepatic fat accumulation and progresses to hepatic inflammation, termed as non-alcoholic steatohepatitis (NASH), hepatic fibrosis/cirrhosis, and finally leading to NAFLD-related hepatocellular carcinoma (NAFLD-HCC). Accumulating evidence showed that the gut microbiome plays a vital role in the initiation and progression of NAFLD through the gut–liver axis. The gut–liver axis is the mutual communication between gut and liver comprising the portal circulation, bile duct, and systematic circulation. The gut microbiome dysbiosis contributes to NAFLD development by dysregulating the gut–liver axis, leading to increased intestinal permeability and unrestrained transfer of microbial metabolites into the liver. In this review, we systematically summarized the up-to-date information of gut microbiome dysbiosis and metabolomic changes along the stages of steatosis, NASH, fibrosis, and NAFLD-HCC. The components and functions of the gut–liver axis and its association with NAFLD were then discussed. In addition, we highlighted current knowledge of gut microbiome-based treatment strategies targeting the gut–liver axis for preventing NAFLD and its associated HCC.
Fibrin, Bone Marrow Cells and Macrophages Interactively Modulate Cardiomyoblast Fate
Authors: Borrego Inês , Frobert Aurélien , Ajalbert Guillaume , Valentin Jérémy , Kaltenrieder Cyrielle , Fellay Benoît , Stumpe Michael , Cook Stéphane , Dengjel Joern , Giraud Marie-Noëlle
Published: February 2022

Interactions between macrophages, cardiac cells and the extracellular matrix are crucial for cardiac repair following myocardial infarction (MI). We hypothesized that cell-based treatments might modulate these interactions. After validating that bone marrow cells (BMC) associated with fibrin lowered the infarct extent and improved cardiac function, we interrogated the influence of fibrin, as a biologically active scaffold, on the secretome of BMC and the impact of their association on macrophage fate and cardiomyoblast proliferation. In vitro, BMC were primed with fibrin (F-BMC). RT-PCR and proteomic analyses showed that fibrin profoundly influenced the gene expression and the secretome of BMCs. Consequently, the secretome of F-BMC increased the spreading of cardiomyoblasts and showed an alleviated immunomodulatory capacity. Indeed, the proliferation of anti-inflammatory macrophages was augmented, and the phenotype of pro-inflammatory switched as shown by downregulated Nos2, Il6 and IL1b and upregulated Arg1, CD163, Tgfb and IL10. Interestingly, the secretome of F-BMC educated-macrophages stimulated the incorporation of EdU in cardiomyoblasts. In conclusion, our study provides evidence that BMC/fibrin-based treatment improved cardiac structure and function following MI. In vitro proofs-of-concept reveal that the F-BMC secretome increases cardiac cell size and promotes an anti-inflammatory response. Thenceforward, the F-BMC educated macrophages sequentially stimulated cardiac cell proliferation.
In Vivo Metabolic Analysis of the Anticancer Effects of Plasma-Activated Saline in Three Tumor Animal Models
Authors: Qi Miao , Xu Dehui , Wang Shuai , Li Bing , Peng Sansan , Li Qiaosong , Zhang Hao , Fan Runze , Chen Hailan , Kong Michael G.
Published: February 2022

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.
Microsphere Peptide-Based Immunoassay for the Detection of Recombinant Bovine Somatotropin in Injection Preparations
Authors: Smits Nathalie G. E. , Bovee Toine F. H. , Pujari Sidharam P. , van Ginkel Leendert A. , Nielen Michel W. F. , Albada Bauke
Published: February 2022

The use of peptides in immunoassays can be favored over the use of the full protein when more cost effective or less toxic approaches are needed, or when access to the full protein is lacking. Due to restricted access to recombinant bovine somatotropin (rbST), a protein enhancing growth and lactating performances of livestock, which use has been banned in the EU, Canada and Australia (amongst others), we developed a peptide-based biorecognition assay on an imaging planar array analyzer. For this, we identified the rbST epitope that is responsible for binding to the rbST-targeting monoclonal antibody 4H12 (MAb 4H12) to be 115DLEEGILALMR125. This linear peptide was synthesized and coupled to microspheres, after which it was tested in a biorecognition competitive inhibition assay format. We observed IC50 values of approximately 0.11 μg mL−1, which are lower than observed for the full rbST protein (IC50 = 0.20 μg mL−1). Importantly, there was no binding with the scrambled peptide. Preliminary results of directly coupled peptides in a microsphere biorecognition assay for detection of rbST are presented. Real-life applicability for detection of somatotropins (STs) in injection preparations of bovine-, porcine- and equine ST are shown. This newly developed immunoassay strongly supports future developments of peptide-based immunoassays to circumvent the limited access to the full protein.
Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder in Comparison to the Treatment of Unipolar Depression in a Naturalistic Setting
Authors: Alhelali Abdullah , Almheiri Eisa , Abdelnaim Mohamed , Weber Franziska C. , Langguth Berthold , Schecklmann Martin , Hebel Tobias
Published: February 2022

Repetitive transcranial magnetic stimulation (rTMS) is effective in the treatment of depression. However, for the subset of patients with bipolar disorder, less data is available and overall strength of evidence is weaker than for its use in unipolar depression. A cohort of 505 patients (of which 46 had a diagnosis of bipolar disorder) with depression who were treated with rTMS were analyzed retrospectively with regards to their response to several weeks of treatment. Hamilton Depression Rating Scale (HDRS) was assessed as main outcome. Unipolar and bipolar patients with depression did not differ significantly in baseline demographic variables or severity of depression. Both groups did not differ significantly in their response to treatment as indicated by absolute and relative changes in the HDRS and response and remission rates. On HDRS subitem-analysis, bipolar patients showed superior amelioration of the symptom “paranoid symptoms” in a statistically significant manner. In conclusion, depressed patients with a diagnosis of bipolar disorder benefit from rTMS in a similar fashion as patients with unipolar depression in a naturalistic setting. rTMS might be more effective in reducing paranoia in bipolar than in unipolar patients.
Your Money or Your Sense of Smell? A Comparative Analysis of the Sensory and Psychological Value of Olfaction
Authors: Herz Rachel S. , Bajec Martha R.
Published: February 2022

In public discourse, the sense of smell is typically characterized as the least important of the five senses. However, there are very little empirical data on this topic. Recently, much more attention has been brought to the sense of smell since olfactory dysfunction is a primary and often long-term symptom of COVID-19 infection. It was therefore of interest to expand research on the perceived value of olfaction in the current cultural condition. We developed a survey that directly compared the value of the senses of smell, hearing, and vision with each other and in relation to nine common items representing digital, material, personal, and physical commodities of varying social and emotional meaningfulness (phone, $10,000, favorite social media, online shopping, favorite streaming service, dream vacation, pet, hair, little left toe). In total, four hundred and seven female and male respondents comprising two life-stage groups (college students, general public adults) participated in our online survey study during winter–spring of 2021. The results reveal that the sense of smell was perceived as vastly less important than vision and hearing and much less valuable than various common commodities. We also found that life-stage and gender mediated our findings. For example, one-quarter of the college student respondents would give up their sense of smell in order to keep their phone and nearly half of all women would give up their sense of smell to keep their hair. Our data further illustrate that the senses of vision and hearing are valued relatively similarly. A number of questions arise from the present data and suggestions for ways in which our survey can be expanded and altered to address further research are discussed.
Pain in Persons with Disorders of Consciousness
Authors: Zasler Nathan D. , Formisano Rita , Aloisi Marta
Published: February 2022

Pain and suffering in persons with disorders of consciousness (DoC) remain poorly understood, frequently unaddressed or inadequately addressed, and controversial on numerous levels. This narrative literature review will address a number of critical issues germane to pain and suffering in this challenging group of patients, providing an introductory overview of the topic, perspectives on current knowledge regarding pain pathoanatomy and pathophysiology, and a review of common pain generators and factors that can lead to the chronifcation of pain. Caveats on bedside pain assessment challenges, as well as electrophysiologic and neuroimaging findings in these patients, will also be explored. Pain management techniques, including non-pharmacological and pharmacological, will be reviewed. Ethical considerations in the context of pain and suffering in persons with disorders of consciousness will round out the review prior to our concluding comments.
Assessment of Strength Reduction Factor on Concrete Moment Frames According to the New Venezuelan Seismic Code
Authors: Mata-Lemus Ramón , Idrees-Rustom Ahmad , Sánchez-Rodríguez Javier , Torres-Moreno Ronald , Nuñez-Castellanos Eduardo , Bustamante-Laissle Guillermo
Published: February 2022

Nonlinear static analysis is a validated tool for the seismic evaluation of existing and new structures, specifically for reinforced concrete buildings. In order to assess the performance of reinforced concrete frames designed according to the new Venezuelan seismic code, configurations of low-, medium-, and high-rise concrete buildings are subjected to 20 different load patterns considering the nonlinear behavior according to FEMA P695. A total of 140 concrete frame models were analyzed using modal response spectrum analysis and nonlinear static pushover analysis. The parameters considered for analyzing the models were the response reduction factor (R), the overstrength factor (RΩ), and the ductility factor (Rµ). The results showed a performance controlled by ductile failure mechanisms in low-rise models unlike combined failure mechanisms with columns with plastic hinge in high-rise models. Reduction factor values between 4 and 14 were obtained. In addition, the pushover curves were affected by the load patterns; therefore, it was necessary to identify the representative patterns, refusing the rest of the patterns. A statistical adjustment was performed using a log-normal distribution. The strength reduction factor specified in the new Venezuelan code was higher than the values obtained for the 95% confidence levels according to the distribution assumed in the reinforced concrete frames models. Finally, the strength reduction factor more representative is R = 4.
Lateral Pressure Test of Vertical Joint Concrete and Formwork Optimization Design for Monolithic Precast Concrete Structure
Authors: Yang Yabin , Ding Xinxin , Liu Yungao , Deng Lianchao , Lv Feiyang , Zhao Shunbo
Published: February 2022

When the vertical joints of monolithic precast concrete structures are cast by self-compacting concrete, the design of the formwork under rational lateral pressure of self-compacting concrete becomes a key technical issue. In this paper, a prototype simulation test was conducted for the pouring of self-compacting concrete in the vertical joint of precast concrete walls. The self-compacting concrete was continuously poured from the top of vertical joints with a height of 2.8 m without any assistance such as a delivery tube. The formwork pressure of self-compacting concrete was measured at different heights with varying casting time. Results showed that the lateral pressure increased with the increase in slump-flow of fresh self-compacting concrete, reaching a peak value of about 70 kPa at a height of about 600 mm from the bottom of formwork. Compared to the concrete with a slump-flow of 550 mm, the self-compacting concrete with the slump-flow reached 655 mm and 755 mm, presenting an increase in the peak lateral pressure by 31.5% and 44.9%, respectively. A method for calculating the lateral pressure of self-compacting concrete on the joint formwork is proposed using the analysis of enveloped test curves. Under the condition with enough strength and limited deformation of the joint formwork, the optimal design of aluminum alloy formwork is determined using finite element analysis. This provides a sci-tech foundation of the optimal design to lighten the weight of joint formwork to improve the installation efficiency and reduce the manual power cost.
Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review
Authors: Kamran Sareh , Sinniah Ajantha , Abdulghani Mahfoudh A. M. , Alshawsh Mohammed Abdullah
Published: February 2022

Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents for cancer remains a priority to increase the range of effective treatments. Terpenoids, a large group of secondary metabolites, are derived from plant sources and are composed of several isoprene units. The high diversity of terpenoids has drawn attention to their potential anticancer and pharmacological activities. Some terpenoids exhibit an anticancer effect by triggering various stages of cancer progression, for example, suppressing the early stage of tumorigenesis via induction of cell cycle arrest, inhibiting cancer cell differentiation and activating apoptosis. At the late stage of cancer development, certain terpenoids are able to inhibit angiogenesis and metastasis via modulation of different intracellular signaling pathways. Significant progress in the identification of the mechanism of action and signaling pathways through which terpenoids exert their anticancer effects has been highlighted. Hence, in this review, the anticancer activities of twenty-five terpenoids are discussed in detail. In addition, this review provides insights on the current clinical trials and future directions towards the development of certain terpenoids as potential anticancer agents.
Overall Survival of Patients with Myxofibrosarcomas: An Epidemiological Study
Authors: van der Horst Chiel A. J. , Bongers Sabien L. M. , Versleijen-Jonkers Yvonne M. H. , Ho Vincent K. Y. , Braam Pètra M. , Flucke Uta E. , de Wilt Johannes H. W. , Desar Ingrid M. E.
Published: February 2022

Myxofibrosarcoma (MFS) is a rare mesenchymal soft tissue sarcoma type, with a high local recurrence (LR) rate. Robust epidemiological data on MFS are lacking. We, therefore, aimed to identify prognostic factors and describe real-life outcomes of a large cohort of 908 MFS patients obtained from the nationwide database of the Netherlands Cancer Registry and diagnosed between 2002 and 2019. Median Overall survival (OS) was 155 (range 0.1–215) months, with a five-year OS of 67.7%. No improvement of OS was found over time. Multivariable Cox regression survival analysis demonstrated known prognostic factors for OS, such as older age, tumour size, and histological grade with the addition of sex. Surgery at sarcoma expertise centres, instead of general hospitals, was associated with better OS outcomes. In a subcohort of 177 patients, 39% developed LR with a median time to recurrence of 20 months. From LR on, the median OS was 64.0 months (CI 95% 38.5–89.5). In 28%, distant metastases were diagnosed with a median OS of 34.3 months (CI 95% 28.8–39.8) after diagnosis of the primary tumour. In this largest nationwide cohort so far, survival outcomes and recurrence rates for MFS patients did not improve over time, emphasizing the need to improve treatment strategies and suggesting a role for sarcoma expertise centres.
Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway
Authors: Markowitsch Sascha D. , Vakhrusheva Olesya , Schupp Patricia , Akele Yasminn , Kitanovic Jovana , Slade Kimberly S. , Efferth Thomas , Thomas Anita , Tsaur Igor , Mager René , Haferkamp Axel , Juengel Eva
Published: February 2022

Therapy resistance remains a major challenge in treating advanced renal cell carcinoma (RCC), making more effective treatment strategies crucial. Shikonin (SHI) from traditional Chinese medicine has exhibited antitumor properties in several tumor entities. We, therefore, currently investigated SHI’s impact on progressive growth and metastatic behavior in therapy-sensitive (parental) and therapy-resistant Caki-1, 786-O, KTCTL-26, and A498 RCC cells. Tumor cell growth, proliferation, clonogenic capacity, cell cycle phase distribution, induction of cell death (apoptosis and necroptosis), and the expression and activity of regulating and signaling proteins were evaluated. Moreover, the adhesion and chemotactic activity of the RCC cells after exposure to SHI were investigated. SHI significantly inhibited the growth, proliferation, and clone formation in parental and sunitinib-resistant RCC cells by G2/M phase arrest through down-regulation of cell cycle activating proteins. Furthermore, SHI induced apoptosis and necroptosis by activating necrosome complex proteins. Concomitantly, SHI impaired the AKT/mTOR pathway. Adhesion and motility were cell line specifically affected by SHI. Thus, SHI may hold promise as an additive option in treating patients with advanced and therapy-resistant RCC.