bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them
Authors: Santos-Aberturas Javier , Vior Natalia
Published: February 2022

Bacterial secondary metabolites represent an invaluable source of bioactive molecules for the pharmaceutical and agrochemical industries. Although screening campaigns for the discovery of new compounds have traditionally been strongly biased towards the study of soil-dwelling Actinobacteria, the current antibiotic resistance and discovery crisis has brought a considerable amount of attention to the study of previously neglected bacterial sources of secondary metabolites. The development and application of new screening, sequencing, genetic manipulation, cultivation and bioinformatic techniques have revealed several other groups of bacteria as producers of striking chemical novelty. Biosynthetic machineries evolved from independent taxonomic origins and under completely different ecological requirements and selective pressures are responsible for these structural innovations. In this review, we summarize the most important discoveries related to secondary metabolites from alternative bacterial sources, trying to provide the reader with a broad perspective on how technical novelties have facilitated the access to the bacterial metabolic dark matter.
Hypertension Prediction in Adolescents Using Anthropometric Measurements: Do Machine Learning Models Perform Equally Well?
Authors: Chai Soo See , Goh Kok Luong , Cheah Whye Lian , Chang Yee Hui Robin , Ng Giap Weng
Published: February 2022

The use of anthropometric measurements in machine learning algorithms for hypertension prediction enables the development of simple, non-invasive prediction models. However, different machine learning algorithms were utilized in conjunction with various anthropometric data, either alone or in combination with other biophysical and lifestyle variables. It is essential to assess the impacts of the chosen machine learning models using simple anthropometric measurements. We developed and tested 13 machine learning methods of neural network, ensemble, and classical categories to predict hypertension in adolescents using only simple anthropometric measurements. The imbalanced dataset of 2461 samples with 30.1% hypertension subjects was first partitioned into 90% for training and 10% for validation. The training dataset was reduced to eight simple anthropometric measurements: age, C index, ethnicity, gender, height, location, parental hypertension, and waist circumference using correlation coefficient. The Synthetic Minority Oversampling Technique (SMOTE) combined with random under-sampling was used to balance the dataset. The models with optimal hyperparameters were assessed using accuracy, precision, sensitivity, specificity, F1-score, misclassification rate, and AUC on the testing dataset. Across all seven performance measures, no model consistently outperformed the others. LightGBM was the best model for all six performance metrics, except sensitivity, whereas Decision Tree was the worst. We proposed using Bayes’ Theorem to assess the models’ applicability in the Sarawak adolescent population, resulting in the top four models being LightGBM, Random Forest, XGBoost, and CatBoost, and the bottom four models being Logistic Regression, LogitBoost, SVM, and Decision Tree. This study demonstrates that the choice of machine learning models has an effect on the prediction outcomes.
Verification of 3D AE Source Location Technique in Triaxial Compression Tests Using Pencil Lead Break Sources on a Cylindrical Metal Specimen
Authors: Li Xianfeng , Naqi Ali , Maqsood Zain , Koseki Junichi
Published: February 2022

Recently, the acoustic emission (AE) technique has been widely applied in the field of geotechnical engineering. One of the main applications of this technique is to locate damage sources, which is known as the AE source location technique. In this research, the 3D AE source location technique based on the time difference of arrival is verified by conducting pencil lead break (PLB) tests on a cylindrical metal specimen. From the results of this study, the existing method is proven to have the least error in terms of distance from the coordinate origin, but with some errors along x, y, and z axes. When the PLB sources originate in the middle part of the specimen, the calculated result has a higher accuracy, as compared to other positions. It seems that the calculated AE sources tend to be concentrated on the central part with some errors. Moreover, outside noises induced by a hammer hit have virtually no effect on this AE source location technique.
How Can a Clinical Data Modelling Tool Be Used to Represent Data Items of Relevance to Paediatric Clinical Trials? Learning from the Conect4children (c4c) Consortium
Authors: Amadi Chima , Leary Rebecca , Palmeri Avril , Hedley Victoria , Sen Anando , Siddiqui Rahil Qamar , Kalra Dipak , Straub Volker
Published: February 2022

Data dictionaries for clinical trials are often created manually, with data structures and controlled vocabularies specific for a trial or family of trials within a sponsor’s portfolio. Microsoft Excel is commonly used to capture the representation of data dictionary items but has limited functionality for this purpose. The conect4children (c4c) network is piloting the Direcht clinical data modelling tool to model their Cross Cutting Paediatric Data Dictionary (CCPDD) in a more formalised way. The first pilot had the key objective of testing whether a clinical data modelling tool could be used to represent data items from the CCPDD. The key objective of the second pilot is to establish whether a small team with little or no experience of clinical data modelling can use Direcht to expand the CCPDD. Clinical modelling is the process of structuring clinical data so it can be understood by computer systems and humans. The model contains all of the elements that are needed to define the data item. Results from the pilots show that Direcht creates a structured environment to build data items into models that fit into the larger CCPDD. Models can be represented as an HTML document, mind map, or exported in various formats for import into a computer system. Challenges identified over the course of both pilots are being addressed with c4c partners and external stakeholders.
Dual-ISM: Duality-Based Image Sequence Matching for Similar Image Search
Authors: Lee Hye-Jin , Kwon Yongjin , Ihm Sun-Young
Published: February 2022

In this paper, we propose the duality-based image sequence matching method, which is called Dual-ISM, a subsequence matching method for searching for similar images. We first extract feature points from the given image data and configure the feature vectors as one data sequence. Next, the feature vectors are configured in the form of a disjoint window, and a low-dimensional transformation is carried out. Subsequently, the query image that is entered to construct the candidate set is similarly subjected to a low-dimensional transformation, and the low-dimensional transformed window of the data sequence and window that are less than the allowable value, ε, is regarded as the candidate set using a distance calculation. Finally, similar images are searched in the candidate set using the distance calculation that are based on the original feature vector.
Sgraffito as a Method of Wall Decoration in the Renaissance and Mannerist Silesia
Authors: Jagiełło Marzanna
Published: February 2022

During the Renaissance and Mannerist periods, in most European countries the fashion for decorating walls with sgraffiti covered a large part of continent, from Portugal to Romania, and from Central Italy to the German countries and Poland. Its popularity in the middle part of Europe peaked in the 16th and 17th centuries. In many regions, sgraffito was the dominant method of decorating buildings. Sgraffito styles were differentiated by design, artistic level, local conditions and investor preferences. In many regions north of the Alps, sgraffito decorations were, on the one hand, a frequently used method of modernizing medieval buildings, and, on the other, a form of expressing views, often religious ones. Everywhere, however, they expressed supranational belonging to the world of a post-medieval, revival community. It was no different in Silesia, where the sgraffiti madness arrived, thanks to artists who came from the northern regions of Italy around 1540 and settled down until the middle of the next century. The research carried out by the author has proven that, for Silesia, sgraffito was an iconic sign of the architecture of that period. In this region, then belonging to the Habsburg Monarchy, sgraffito decorations covered a wide variety of architectural objects, from barns, walls, and gates to tenement houses, manors, castles, and churches. In the case of the latter, research has shown that temples in Gothic style are heavily decorated with sgraffiti, which should be considered a distinctive feature when compared to other regions. At the same time, it was found that the vast majority of them appeared in forms and themes known to us from other countries covered by the sgraffito fashion. The frame composition made in this technique and, most probably modeled directly on the template by S. Serlia (Tutte L’opere d’Architettura et Prospettiva) from 1619, should be considered as the Silesian contribution to the sgraffito heritage as well as oval bossages. While studying Silesian sgraffito, some local technological differences were also noticed. With the advent of the Baroque period, a large part of the sgraffito decoration was covered (and thus preserved) with a new, baroque decorative costume. We still discover them in the present while carrying out conservation works (sometimes multiple) on historic buildings. Many others, those constantly on display, have been restored to preserve their original shape, or have been reconstructed. Various and simultaneously modernized methods are used to implement these works. Their correct selection depends on in-depth knowledge of sgraffito (historical, artistic, technological and technical) and their regional specificity. It also depends on the constant exchange of experiences between all those dealing with sgraffito heritage.
Performance Assessment and Modeling of Routing Protocol in Vehicular Ad Hoc Networks Using Statistical Design of Experiments Methodology: A Comprehensive Study
Authors: Ajjaj Souad , El Houssaini Souad , Hain Mustapha , El Houssaini Mohammed-Alamine
Published: February 2022

The performance assessment of routing protocols in vehicular ad hoc networks (VANETs) plays a critical role in testing the efficiency of the routing algorithms before deployment in real conditions. This research introduces the statistical design of experiments (DOE) methodology as an innovative alternative to the one factor at a time (OFAT) approach for the assessment and the modeling of VANET routing protocol performance. In this paper, three design of experiments methods are applied, namely the two-level full factorial method, the Plackett–Burman method and the Taguchi method, and their outcomes are comprehensively compared. The present work considers a case study involving four factors namely: node density, number of connections, black hole and worm hole attacks. Their effects on four measured outputs called responses are simultaneously evaluated: throughput, packet loss ratio, average end-to-end delay and routing overhead of the AODV routing protocol. Further, regression models using the least squares method are generated. First, we compare the main effects of factors resulted from the three DOE methods. Second, we perform analysis of variance (ANOVA) to explore the statistical significance and compare the percentage contributions of each factor. Third, the goodness of fit of regression models is assessed using the adjusted R-squared measure and the fitting plots of measured versus predicted responses. VANET simulations are implemented using the network simulator (NS-3) and the simulator of urban mobility (SUMO). The findings reveal that the design of experiments methodology offers powerful mathematical, graphical and statistical techniques for analyzing and modeling the performance of VANET routing protocols with high accuracy and low costs. The three methods give equivalent results in terms of the main effect and ANOVA analysis. Nonetheless, the Taguchi models show higher predictive accuracy.
Low-Cost Devices for Three-Dimensional Cell Aggregation, Real-Time Monitoring Microscopy, Microfluidic Immunostaining, and Deconvolution Analysis
Authors: Struber Andreas , Auer Georg , Fischlechner Martin , Wickstrom Cody , Reiter Lisa , Lutsch Eric , Simon-Nobbe Birgit , Marozin Sabrina , Lepperdinger Günter
Published: February 2022

The wide use of 3D-organotypic cell models is imperative for advancing our understanding of basic cell biological mechanisms. For this purpose, easy-to-use enabling technology is required, which should optimally link standardized assessment methods to those used for the formation, cultivation, and evaluation of cell aggregates or primordial tissue. We thus conceived, manufactured, and tested devices which provide the means for cell aggregation and online monitoring within a hanging drop. We then established a workflow for spheroid manipulation and immune phenotyping. This described workflow conserves media and reagent, facilitates the uninterrupted tracking of spheroid formation under various conditions, and enables 3D-marker analysis by means of 3D epifluorescence deconvolution microscopy. We provide a full description of the low-cost manufacturing process for the fluidic devices and microscopic assessment tools, and the detailed blueprints and building instructions are disclosed. Conclusively, the presented compilation of methods and techniques promotes a quick and barrier-free entry into 3D cell biology.
Recent Advances in Plant Metabolomics: From Metabolic Pathways to Health Impact
Authors: Figueiredo Andreia , Hugueney Philippe , Durazzo Alessandra
Published: February 2022

In the past decade, technological development allowed a rapid advance on several OMIC approaches, metabolomics was no exception [...]
Cycloastragenol Inhibits Experimental Abdominal Aortic Aneurysm Progression
Authors: Melin Leander Gaarde , Dall Julie Husted , Lindholt Jes S. , Steffensen Lasse B. , Beck Hans Christian , Elkrog Sophie L. , Clausen Pernille D. , Rasmussen Lars Melholt , Stubbe Jane
Published: February 2022

The pathogenesis of abdominal aortic aneurysm involves vascular inflammation and elastin degradation. Astragalusradix contains cycloastragenol, which is known to be anti-inflammatory and to protect against elastin degradation. We hypothesized that cycloastragenol supplementation inhibits abdominal aortic aneurysm progression. Abdominal aortic aneurysm was induced in male rats by intraluminal elastase infusion in the infrarenal aorta and treated daily with cycloastragenol (125 mg/kg/day). Aortic expansion was followed weekly by ultrasound for 28 days. Changes in aneurysmal wall composition were analyzed by mRNA levels, histology, zymography and explorative proteomic analyses. At day 28, mean aneurysm diameter was 37% lower in the cycloastragenol group (p < 0.0001). In aneurysm cross sections, elastin content was insignificantly higher in the cycloastragenol group (10.5% ± 5.9% vs. 19.9% ± 16.8%, p = 0.20), with more preserved elastin lamellae structures (p = 0.0003) and without microcalcifications. Aneurysmal matrix metalloprotease-2 activity was reduced by the treatment (p = 0.022). Messenger RNA levels of inflammatory- and anti-oxidative markers did not differ between groups. Explorative proteomic analysis showed no difference in protein levels when adjusting for multiple testing. Among proteins displaying nominal regulation were fibulin-5 (p = 0.02), aquaporin-1 (p = 0.02) and prostacyclin synthase (p = 0.007). Cycloastragenol inhibits experimental abdominal aortic aneurysm progression. The suggested underlying mechanisms involve decreased matrix metalloprotease-2 activity and preservation of elastin and reduced calcification, thus, cycloastragenol could be considered for trial in abdominal aortic aneurysm patients.
Integrative Identification of Genetic Loci Jointly Influencing Diabetes-Related Traits and Sleep Traits of Insomnia, Sleep Duration, and Chronotypes
Authors: Ma Yujia , Zhou Zechen , Li Xiaoyi , Yan Zeyu , Ding Kexin , Xiao Han , Wu Yiqun , Wu Tao , Chen Dafang
Published: February 2022

Accumulating evidence suggests a relationship between type 2 diabetes mellitus and sleep problems. A comprehensive study is needed to decipher whether shared polygenic risk variants exist between diabetic traits and sleep traits. Methods: We integrated summary statistics from different genome-wide association studies and investigated overlap in single-nucleotide polymorphisms (SNPs) associated with diabetes-related traits (type 2 diabetes, fasting glucose, fasting insulin, and glycated hemoglobin) and sleep traits (insomnia symptoms, sleep duration, and chronotype) using a conditional/conjunctional false discovery rate approach. Pleiotropic genes were further evaluated for differential expression analysis, and we assessed their expression pattern effects on type 2 diabetes by Mendelian randomization (MR) analysis. Results: We observed extensive polygenic pleiotropy between diabetic traits and sleep traits. Fifty-eight independent genetic loci jointly influenced the risk of type 2 diabetes and the sleep traits of insomnia, sleep duration, and chronotype. The strongest shared locus between type 2 diabetes and sleep straits was FTO (lead SNP rs8047587). Type 2 diabetes (z score, 16.19; P = 6.29 × 10−59) and two sleep traits, sleep duration (z score, −6.66; P = 2.66 × 10−11) and chronotype (z score, 7.42; P = 1.19 × 10−13), were shared. Two of the pleiotropic genes, ENSA and PMPCA, were validated to be differentially expressed in type 2 diabetes, and PMPCA showed a slight protective effect on type 2 diabetes in MR analysis. Conclusions: Our study provided evidence for the polygenic overlap between diabetic traits and sleep traits, of which the expression of PMPCA may play a crucial role and provide support of the hazardous effect of being an “evening” person on diabetes risk.
Ion-Imprinted Polymer-on-a-Sensor for Copper Detection
Authors: Gerdan Zeynep , Saylan Yeşeren , Uğur Mukden , Denizli Adil
Published: February 2022

The accumulation of metal ions in the body is caused by human activities and industrial uses. Among these metal ions, copper is the third most abundant ion found in the human body and is indispensable for health because it works as a catalyst in the iron absorption processes. However, high doses of copper ions have been reported to generate various diseases. Different types of sensors are used to detect metal ions for several applications. To design selective and specific recognition sites on the sensor surfaces, molecular imprinting is one of the most used alteration methods to detect targets by mimicking natural recognition molecules. In this study, an ion-imprinted polymer-integrated plasmonic sensor was prepared to selectively detect copper (Cu(II)) ions in real-time. Following different characterization experiments, the Cu(II)-imprinted plasmonic sensor was employed for kinetic, selectivity, and reusability studies. According to the results, it was observed that this sensor can measure with 96% accuracy in the Cu(II) concentration range of 0.04–5 μM in buffer solution. The limit of detection and limit of quantification values were computed as 0.027 µM and 0.089 µM. The results also showed that this plasmonic sensor works successfully not only in a buffer solution but also in complex media such as plasma and urine.
Cathemeral Behavior of Piping Plovers (Charadrius melodus) Breeding along Michigan’s Lake Superior Shoreline
Authors: Waterman Riley , Garvon Jason
Published: February 2022

Shorebirds commonly exhibit cathemeral activity and commonly forage throughout a 24 h period. Conservation of endangered shorebirds should then extend to protection at night, yet little data exists on overall time budgets of such species at night. The Great Lakes population of piping plovers (Charadrius melodus) is the smallest and most endangered, making each breeding pair an essential part of recovery. Intense monitoring of breeding individuals occurs during the daytime, yet we have little understanding of the time budgets of plovers at night. To gain better insight into the cathemeral behavior of plovers we recorded behaviors of 12 plovers from along Michigan’s Lake Superior shoreline during both day and night in 2018 with the use of a night-vision-capable camera, and compared time budgets of plovers between daytime and nighttime. Overall, piping plovers spent more time and a greater proportion of their time foraging at night and more time devoted to being alert during the day. These differences were especially evident during the chick rearing phase. Limited observations suggest that copulatory activity may also be more common at night. Likely, the threat of avian predation on this population drives the increase in nighttime foraging, despite decreased efficiency. Recognizing the importance of decreasing potential for disturbance during the night should be considered in future management strategies regarding the recovery of this endangered species.
Life Cycle Assessment Meeting Energy Standard Performance: An Office Building Case Study
Authors: Pushkar Svetlana , Yezioro Abraham
Published: February 2022

Transitioning from fossil to renewable energies, particularly photovoltaic (PV) energy, could influence building design in terms of environmental evaluation. The aim of this study was to rate a typical office building that complies with the Israeli Standard SI5282, Energy Rating of Buildings, and to evaluate it by life cycle assessment (LCA). An office building in Tel Aviv with four exterior wall construction technologies was modeled as follows: (1) a concrete-block-based wall with minimal windows; (2) a concrete-block-based wall with maximal windows; (3) an autoclaved aerated-block-based wall with minimal windows; and (4) an autoclaved aerated-block-based wall with maximal windows. The electricity sources used to support the building’s operational energy were: (i) 31% coal, 56% natural gas, and 13% PV (adopted in 2020); (ii) 8% coal, 57% natural gas, and 35% PV (planned for 2025); and (iii) 100% PV (planned for the future). A two-stage nested mixed analysis of variance was used to simultaneously evaluate the results of six ReCiPe2016 methodologies. The results show that as fossil fuels are replaced by PV energy production, there is a greater need to use LCA methodology in building design in conjunction with energy standards. The energy rating is recommended to be carried out with an environmental assessment of the production stage of construction. Ignoring the LCA results could lead to the misinterpretation of a building’s sustainability.
Estimation of Floor Response Spectra for Self-Centering Structural Systems with Flag-Shaped Hysteretic Behavior
Authors: Shrestha Binod Kumar , Wijeyewickrema Anil C. , Miyashita Hiroki , Malla Niraj
Published: February 2022

Spectral floor-acceleration demands are necessary for the seismic design of acceleration-sensitive non-structural components (NSCs). Existing studies to estimate floor response spectra (FRS) using empirical equations are based on elasto-plastic and stiffness degrading hysteretic behavior of the primary structure. In the present study, the FRS for self-centering (SC) structural systems with flag-shaped hysteretic behavior under far-fault ground motions are investigated. The FRS and dynamic amplification factor (DAF) are obtained from nonlinear response history analysis (NLRHA) of SC structural systems with flag-shaped hysteretic behavior. An equation to estimate the FRS is proposed and verified by carrying out NLRHA using a different set of far-fault ground motions. The equation to estimate FRS is shown to predict floor acceleration demands with very good accuracy.
The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions
Authors: Robak Tadeusz , Witkowska Magda , Smolewski Piotr
Published: February 2022

The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKis are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib was the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies have evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in early-phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, and drug–drug interactions associated with the treatment of CLL with BTK inhibitors and examines their further implications.
Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe
Authors: Carbó-Bagué Anna , Rubió-Casadevall Jordi , Puigdemont Montserrat , Sanvisens Arantza , Oliveras Glòria , Coll Mònica , del Olmo Bernat , Perez-Bueno Ferran , Marcos-Gragera Rafael
Published: February 2022

Background: Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma’s mutational profile can help to develop target therapies in advanced disease or adjuvant settings. Methods: We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994–2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel. Results: Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found. Conclusion: Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials.
The Roles of Platelet-Activating Factor and Magnesium in Pathophysiology of Hypertension, Atherogenesis, Cardiovascular Disease, Stroke and Aging
Authors: Shah Nilank , Sethi Roshni , Shah Sachin , Jafri Komail , Duran Jonah , Chang Yong , Soni Chirag , Wollocko Hanna
Published: February 2022

Hypertension and atherosclerosis are debilitating diseases that affect millions each year. Long-term consequences include but are not limited to stroke, myocardial infarction, and kidney failure. Platelet-activating factor (PAF) is a proinflammatory mediator synthesized from a subclass of phosphatidylcholines that increases platelet activation, leukocyte adhesion, infiltration of macrophages, and intracellular lipid accumulation, thereby contributing to atherosclerosis. Magnesium, a key micronutrient and free radical scavenger, is a water-soluble mineral that regulates peripheral vasodilation and calcium, phosphate, and hydroxyapatite homeostasis. Magnesium’s antihypertensive ability stems from its role as a natural calcium antagonist and promoter of vasodilatory mediators, such as nitric oxide. Platelet-activating factor and magnesium share an inverse relationship, and elevated magnesium levels have been shown to have protective effects against plaque formation as well as antihypertensive and antiarrhythmic effects, all of which allow for healthier aging. The purpose of this literature review is to investigate the role of platelet-activating factor and magnesium in the pathophysiology of hypertension, atherosclerosis, cardiovascular disease, stroke, and aging. Since the pathophysiology of the platelet-activating factor biomolecule is underexplored, further research studies are warranted in order to navigate the putative signaling pathways involved in the cardioprotective effects of dietary magnesium as a natural anti-PAF agent.
Heterogeneous Activation of Persulfate by LaMO3 (M=Co, Fe, Cu, Mn, Ni) Perovskite Catalysts for the Degradation of Organic Compounds
Authors: Manos Donatos , Papadopoulou Foteini , Margellou Antigoni , Petrakis Dimitrios , Konstantinou Ioannis
Published: February 2022

Sulfate radical-based advanced oxidation processes (SR-AOPs) are lately applied for the degradation of various pollutants through the formation of reactive oxidant species (ROS) from activation of oxidants, such as persulfate (PS) or peroxymonosulfate (PMS). In this study, LaMO3 (M=Co, Fe, Cu, Mn, Ni) perovskite catalysts were synthesized, characterized by several techniques, and tested for the activation of persulfate towards the degradation of phenolic pollutants. The effect of substitution of position B of La-based perovskites as well as calcination temperature was studied. Overall, the results showed that the decisive role in the catalytic activity was the presence of structures that enhance the transfer of electrons between perovskite and oxidant. LaNiO3 followed by LaCoO3 were found as the most active catalysts. Finally, the stability of the catalysts was studied, showing that B-metal leaching is significant for both catalysts, with LaCoO3 being the most stable one.
Leukocyte Telomere Length Correlates with Extended Female Fertility
Authors: Michaeli Jennia , Smoom Riham , Serruya Noa , El Ayoubi Hosniyah , Rotshenker-Olshinka Keren , Srebnik Naama , Michaeli Ofir , Eldar-Geva Talia , Tzfati Yehuda
Published: February 2022

Current social trends of delayed reproduction to the fourth and fifth decade of life call for a better understanding of reproductive aging. Demographic studies correlated late reproduction with general health and longevity. Telomeres, the protective ends of eukaryotic chromosomes, were implicated in various aging-associated pathologies and longevity. To examine whether telomeres are also associated with reproductive aging, we measured by Southern analysis the terminal restriction fragments (TRF) in leukocytes of women delivering a healthy infant following a spontaneous pregnancy at 43–48 years of age. We compared them to age-matched previously fertile women who failed to conceive above age 41. The average TRF length in the extended fertility group (9350 bp) was significantly longer than in the normal fertility group (8850 bp; p-value = 0.03). Strikingly, excluding women with nine or more children increased the difference between the groups to over 1000 bp (9920 and 8880 bp; p-value = 0.0009). Nevertheless, we observed no apparent effects of pregnancy, delivery, or parity on telomere length. We propose that longer leukocyte telomere length reflects higher oocyte quality, which can compensate for other limiting physiological and behavioral factors and enable successful reproduction. Leukocyte telomere length should be further explored as a novel biomarker of oocyte quality for assessing reproductive potential and integrating family planning with demanding women’s careers.
Mitochondria-Endoplasmic Reticulum Interplay Regulates Exo-Cytosis in Human Neuroblastoma Cells
Authors: Dentoni Giacomo , Naia Luana , Ankarcrona Maria
Published: February 2022

Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) have been emerging as a multifaceted subcellular region of the cell which affects several physiological and pathological mechanisms. A thus far underexplored aspect of MERCS is their contribution to exocytosis. Here, we set out to understand the role of these contacts in exocytosis and find potential mechanisms linking these structures to vesicle release in human neuroblastoma SH-SY5Y cells. We show that increased mitochondria to ER juxtaposition through Mitofusin 2 (Mfn2) knock-down resulted in a substantial upregulation of the number of MERCS, confirming the role of Mfn2 as a negative regulator of these structures. Furthermore, we report that both vesicle numbers and vesicle protein levels were decreased, while a considerable upregulation in exocytotic events upon cellular depolarization was detected. Interestingly, in Mfn2 knock-down cells, the inhibition of the inositol 1,4,5-trisphosphate receptor (IP3R) and the mitochondrial calcium (Ca2+) uniporter (MCU) restored vesicle protein content and attenuated exocytosis. We thus suggest that MERCS could be targeted to prevent increased exocytosis in conditions in which ER to mitochondria proximity is upregulated.
Neurodegenerative Disease-Associated TDP-43 Fragments Are Extracellularly Secreted with CASA Complex Proteins
Authors: Casarotto Elena , Sproviero Daisy , Corridori Eleonora , Gagliani Maria Cristina , Cozzi Marta , Chierichetti Marta , Cristofani Riccardo , Ferrari Veronica , Galbiati Mariarita , Mina Francesco , Piccolella Margherita , Rusmini Paola , Tedesco Barbara , Gagliardi Stella , Cortese Katia , Cereda Cristina , Poletti Angelo , Crippa Valeria
Published: February 2022

Extracellular vesicles (EVs) play a central role in neurodegenerative diseases (NDs) since they may either spread the pathology or contribute to the intracellular protein quality control (PQC) system for the cellular clearance of NDs-associated proteins. Here, we investigated the crosstalk between large (LVs) and small (SVs) EVs and PQC in the disposal of TDP-43 and its FTLD and ALS-associated C-terminal fragments (TDP-35 and TDP-25). By taking advantage of neuronal cells (NSC-34 cells), we demonstrated that both EVs types, but particularly LVs, contained TDP-43, TDP-35 and TDP-25. When the PQC system was inhibited, as it occurs in NDs, we found that TDP-35 and TDP-25 secretion via EVs increased. In line with this observation, we specifically detected TDP-35 in EVs derived from plasma of FTLD patients. Moreover, we demonstrated that both neuronal and plasma-derived EVs transported components of the chaperone-assisted selective autophagy (CASA) complex (HSP70, BAG3 and HSPB8). Neuronal EVs also contained the autophagy-related MAP1LC3B-II protein. Notably, we found that, under PQC inhibition, HSPB8, BAG3 and MAP1LC3B-II secretion paralleled that of TDP-43 species. Taken together, our data highlight the role of EVs, particularly of LVs, in the disposal of disease-associated TDP-43 species, and suggest a possible new role for the CASA complex in NDs.
Machinery and Developmental Role of Retinoic Acid Signaling in Echinoderms
Authors: Yamakawa Shumpei , Wada Hiroshi
Published: February 2022

Although a recent genomic survey revealed its ancient evolutionary origin in the animal kingdom, retinoic acid (RA) signaling was previously thought to be unique to chordates. Echinoderms are of critical interest in researching the evolutionary history of RA signaling, as they represent a basal group of deuterostomes. Furthermore, our previous works have suggested that echinoderms may possess the ancestral function of RA signaling for metamorphosis regulation. In this paper, to facilitate future studies of RA signaling in echinoderms, we provide an overview of RA machinery in echinoderms, identify its signaling components, and discuss its developmental role.
Distinct Actions of the Thyroid Hormone Transporters Mct8 and Oatp1c1 in Murine Adult Hippocampal Neurogenesis
Authors: Mayerl Steffen , Alcaide Martin Andrea , Bauer Reinhard , Schwaninger Markus , Heuer Heike , ffrench-Constant Charles
Published: February 2022

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) result in Allan-Herndon-Dudley Syndrome, a severe form of psychomotor retardation, while inactivating mutations in another TH transporter, organic anion transporting polypeptide 1c1 (OATP1C1), are linked to juvenile neurodegeneration. These diseases point to essential roles for TH transporters in CNS function. We recently defined the presence of Mct8 in adult hippocampal progenitors and mature granule cell neurons and unraveled cell-autonomous and indirect requirements for Mct8 in adult hippocampal neurogenesis. Here, we investigated whether Oatp1c1 is involved in the hippocampal neurogenic process in concert with Mct8. We detected Oatp1c1 gene expression activity and transcripts in subsets of progenitors, neurons and niche cells in the dentate gyrus. Absence of Oatp1c1 resulted in increased neuroblast and reduced immature neuron numbers in 6-month-old Oatp1c1ko and Mct8/Oatp1c1 double knockout (M/Odko) mice. Reduced EdU-label retention in Mct8ko and M/Odko mice confirmed the impact of Mct8 on neuron formation. In contrast, no significant effect of Oatp1c1 loss on granule cell neuron production and anxiety-like behavior in the open field arena were seen. Together, our results reinforce that distinct actions of each TH transporter are required at multiple stages to ensure proper adult hippocampal neurogenesis.
Hypertriglyceridemia Induced Acute Pancreatitis Caused by a Novel LIPC Gene Variant in a Pediatric Patient
Authors: Balanescu Laura , Cardoneanu Ancuta , Stanciu Gabriel , Balanescu Radu , Minulescu Cristian , Pacurar Daniela , Moga Andreea
Published: February 2022

Hypertriglyceridemia induced acute pancreatitis is a rare cause of pancreatitis in children. Hepatic lipase deficiency is an extremely rare cause of hypertriglyceridemia, reported in only a few families to date. Hepatic lipase is the enzyme involved in the hydrolysis of triglycerides and phospholipids in remnants of triglyceride-rich lipoproteins that have a role in the conversion of very low density lipoprotein remnants to low density lipoproteins. Hepatic lipase deficiency is inherited in an autosomal recessive pattern. Detection of heterozygous carriers of hepatic lipase mutations remains accidental at the population level, as affected persons with a heterozygous state of hepatic lipase mutation do not display specific lipoprotein abnormalities and also patients with complete hepatic lipase deficiency have inconstant phenotype. The proximal promoter of the LIPC gene consists of four polymorphic sites in complete linkage disequilibrium. Five missense mutations in encoding exons have been described and proved to be responsible for hepatic lipase deficiency to date: S267F, T383M, L334F, A174T, and R186H, affecting the activity and secretion of hepatic lipase. We identified a primary disorder of the lipid metabolism as the cause of the acute episode of pancreatitis in a four years old patient, consisting of hepatic lipase deficiency caused by a novel genetic variant of the LIPC gene, a gross deletion of the genomic region encompassing exon 1. This variant was not previously described in the literature in persons with LIPC-related disorders and its significance is currently uncertain, but in the presented clinical and paraclinical context, it has the characteristics of a pathological variant inducing a hepatic lipase deficiency phenotype.
Etiology, Risk Factors, and Diagnosis of Back Pain in Children and Adolescents: Evidence- and Consensus-Based Interdisciplinary Recommendations
Authors: Frosch Michael , Mauritz Maximilian D. , Bielack Stefan , Blödt Susanne , Dirksen Uta , Dobe Michael , Geiger Florian , Häfner Renate , Höfel Lea , Hübner-Möhler Bettina , von Kalle Thekla , Lawrenz Burkhard , Leutner Andreas , Mecher Frauke , Mladenov Kiril , Norda Heike , Stahlschmidt Lorin , Steinborn Marc , Stücker Ralf , Trauzeddel Ralf , Trollmann Regina , Wager Julia , Zernikow Boris
Published: February 2022

Using a structured approach and expert consensus, we developed an evidence-based guideline on the diagnosis of back pain and the treatment of non-specific back pain in children and adolescents. The first part comprises etiology, risk factors, and diagnosis. The second part, published in the same issue, includes treatment and prevention. A comprehensive and systematic literature search was conducted to identify relevant guidelines and studies. Based on the findings of this literature search, recommendations on risk factors and diagnosis were formulated and voted on by experts in a structured consensus-building process. Notable red flags for specific back pain and evidence-based risk factors for non-specific back pain in children and adolescents were identified. Only three evidence-based recommendations could be formulated for causes, red flags, and risk factors for back pain, while two recommendations are based on expert consensus. Regarding diagnostics, eight expert consensus recommendations and one evidence-based recommendation could be provided. Despite the importance of adequate diagnosis for the treatment of back pain in children and adolescents, results of this work confirm the deficit in research investment in this area.
A Survey to Understand Parent/Caregiver and Children’s Views on Devices Used for the Administration of Oral Pediatric Medicines in Japan
Authors: Saito Jumpei , Nakamura Hidefumi , Walsh Jennifer , Yamatani Akimasa , Salunke Smita
Published: February 2022

Administration devices are crucial for the correct dosing of medicines to children. In countries outside Japan, oral droppers and syringes are reported to be preferred for the administration of oral liquid medicines to neonates and infants, whilst spoons and cups are more frequently used for older children. However, in Japan the majority of oral medicines are powders and the use of dosing devices in each pediatric age group is not well known. This study was performed as an observational anonymous questionnaire survey on devices for oral medicines in children aged 10 to less than 18 years and parents/caregivers on behalf of children aged from birth to less than 18 years. The results from 336 respondents showed that powders were most frequently prescribed in children aged less than 10 years old followed by liquids. Unlike previous reports, droppers were most frequently used in patients less than 12 months old, while household spoons were most frequently used in older children. Oral syringes were perceived as easy to use, which was in line with previous studies. Further cross-regional multi-countries study for establishment the guidelines on the choice of device will be needed.
Encapsulated EVOO Improves Food Safety and Shelf Life of Refrigerated Pre-Cooked Chicken Nuggets
Authors: Barón-Yusty Marta , Martínez-Hernández Ginés Benito , Ros-Chumillas María , Navarro-Segura Laura , López-Gómez Antonio
Published: February 2022

(1) Background: New clean technologies are needed to reduce the high frying oil waste in the food industry of fried breaded products, together with the obtention of healthier (less fat content) and safer (less microbial growth and acrylamide formation) breaded products; (2) Methods: This study proposes the new technology consisting of incorporation of encapsulated extra virgin olive oil (EVOO) (α-cyclodextrin: EVOO ratio, 1:2.6) in the breadcrumbs (corn breadcrumbs:encapsulated oil ratio, 2:1) for breading chicken nuggets combined with oil-free pre-cooking (baking 150 °C/5 min) and cooking (baking 180 °C/13 min). As controls, a conventional deep-fat frying (180 °C/30 s) and new technology but without encapsulated EVOO were used; (3) Results: Fat content of baked chicken nuggets with the new technology was reduced by 88%, while no sensory differences were scored compared with conventional deep-fat frying. Furthermore, acrylamide formation was reduced by >55% with the new technology. During storage (4 °C) of pre-cooked chicken nuggets of new technology, microbial growth was reduced by 1.4 log units lower compared with deep-fat frying method; (4) Conclusions: the proposed new technology, based on encapsulated EVOO+oil-free pre-cooking/cooking, allows to obtain chicken nuggets that are healthier, safer, and have a longer shelf-life, while frying oil waste is avoided.
Damage Identification for Shear-Type Structures Using the Change of Generalized Shear Energy
Authors: Sun Yun , Yang Qiuwei , Peng Xi
Published: February 2022

Structural damage identification has become an important topic in the field of civil engineering in recent years. The shear-type structure, such as shear frame structure, is a common type used in civil engineering. In this paper, a damage identification method based on the change of generalized shear energy is proposed for shear-type structures. The main steps of the proposed method are as follows. Firstly, the element stiffness matrix in the structural finite element model is decomposed to obtain the elementary shear force vector. Secondly, the elementary generalized shear energy is calculated by the dot product of the vibration mode shape vector and the elementary shear force vector. Thirdly, structural damage locations can be determined by the changes of elementary generalized shear energy. Finally, more accurate damage localization and quantification are achieved by solving the mode shape sensitivity equation. A 20-storey numerical example and a three-storey experimental model are used to demonstrate the proposed damage identification algorithm. From the numerical and experimental results, it was found that the proposed approach can accurately identify the location and extent of the damage in the shear structures even if the data contain noise. It has been shown that the presented algorithm may be useful in the damage identification of shear-type structures.
SiC- and Ag-SiC-Doped Hydroxyapatite Coatings Grown Using Magnetron Sputtering on Ti Alloy for Biomedical Application
Authors: Pana Iulian , Braic Viorel , Vladescu Alina , Ion Raluca , Parau Anca Constantina , Zoita Nicolae Catalin , Dinu Mihaela , Kiss Adrian Emil , Cimpean Anisoara , Braic Mariana
Published: February 2022

SiC- and Ag-SiC-doped hydroxyapatite (HA) coatings were deposited via magnetron sputtering aiming at increased corrosion protection of Ti-10Nb-10Zr-5Ta alloy in simulated body fluid environment and superior mechanical properties compared to plain hydroxyapatite. The coatings had a total thickness of about 350 nm. The X ray diffraction patterns indicate that HA coatings are polycrystalline with a hexagonal structure and the addition of SiC determined the coating amorphization. All coatings presented a lower roughness compared to the Ti alloy and were hydrophilic. Ag-SiC-HA coating presented the best corrosion resistance and tribological parameters. All coatings were biocompatible, as ascertained via indirect cytocompatibility studies conducted on Vero cells.