bluuebunny/crossref_metadata_2025 huggingface dataset:
The Comparative Survey of Coordinated Regulation of Steroidogenic Pathway in Japanese Flounder (Paralichthys olivaceus) and Chinese Tongue Sole (Cynoglossus semilaevis)
Authors: Yang Fan , Wang Yapeng , Lu Wei , Zong Wenyu , Zhu Qing , Cheng Jie
Published: May 2022

Steroidogenesis controls the conversion of cholesterol into steroid hormones through the complex cascade reaction of various enzymes, which play essential roles in sexual differentiation and gonadal development in vertebrates, including teleosts. Japanese flounder (Paralichthys olivaceus) and Chinese tongue sole (Cynoglossus semilaevis) are important marine cultured fishes in China and have remarkable sexual dimorphism with bigger females and sex reversal scenarios from female to neo-male. Several steroidogenic genes have been analyzed individually in the two species, but there is a lack of information on the coordinated interaction of steroidogenic gene regulation. Therefore, in this study, through genomic and transcriptomic analysis, 39 and 42 steroidogenic genes were systematically characterized in P. olivaceus and C. semilaevis genomes, respectively. Phylogenetic and synteny analysis suggested a teleost specific genome duplication origin for cyp19a1a/cyp19a1b, hsd17b12a/hsd17b12b, ara/arb and esr2a/esr2b but not for star/star2 and cyp17a1/cyp17a2. Comparative transcriptome analysis revealed conserved expression patterns for steroidogenic genes in P. olivaceus and C. smilaevis gonads; star/star2, cyp11a/cyp11c, cyp17a1/cyp17a2, cyp21a, hsd3b1, hsd11b and hsd20b were strongly expressed in testis, while cyp19a1a and hsd17b genes were highly expressed in ovaries. Only a few genes were differentially expressed between male and neo-male testis of both P. olivaceus and C. semilaevis, and even fewer genes were differentially regulated in the brains of both species. Network analysis indicated that cyp11c, cyp17a1 and hsd3b1 actively interacted with other steroidogenic genes in P. olivaceus and C. semilaevis, and may play a more sophisticated role in the steroid hormone biosynthesis cascade. The coordinated interaction of steroidogenic genes provided comprehensive insights into steroidogenic pathway regulation with a global biological impact, as well as sexual development in teleost species.
Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes
Authors: Biondi Giuseppina , Marrano Nicola , Borrelli Anna , Rella Martina , Palma Giuseppe , Calderoni Isabella , Siciliano Edoardo , Lops Pasquale , Giorgino Francesco , Natalicchio Annalisa
Published: May 2022

The dysregulation of the β-cell functional mass, which is a reduction in the number of β-cells and their ability to secure adequate insulin secretion, represents a key mechanistic factor leading to the onset of type 2 diabetes (T2D). Obesity is recognised as a leading cause of β-cell loss and dysfunction and a risk factor for T2D. The natural history of β-cell failure in obesity-induced T2D can be divided into three steps: (1) β-cell compensatory hyperplasia and insulin hypersecretion, (2) insulin secretory dysfunction, and (3) loss of β-cell mass. Adipose tissue (AT) secretes many hormones/cytokines (adipokines) and fatty acids that can directly influence β-cell function and viability. As this secretory pattern is altered in obese and diabetic patients, it is expected that the cross-talk between AT and pancreatic β-cells could drive the maintenance of the β-cell integrity under physiological conditions and contribute to the reduction in the β-cell functional mass in a dysmetabolic state. In the current review, we summarise the evidence of the ability of the AT secretome to influence each step of β-cell failure, and attempt to draw a timeline of the alterations in the adipokine secretion pattern in the transition from obesity to T2D that reflects the progressive deterioration of the β-cell functional mass.
Therapeutic Strategies of Biologics in Chronic Rhinosinusitis: Current Options and Future Targets
Authors: Tai Junhu , Han Munsoo , Kim Tae Hoon
Published: May 2022

Chronic rhinosinusitis is a chronic inflammatory disease of the upper airways, for which treatment options include medical or surgical therapy. However, there are limitations to conservative treatment strategies, such as the relapse of nasal polyps. In this review, we discuss the rising role of biomolecular mechanisms associated with various biologics that have been approved or are undergoing clinical trials to treat chronic rhinosinusitis. We also highlight the potential molecular therapeutic targets for managing and treating chronic rhinosinusitis.
Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
Authors: Sepúlveda-Quiñenao Claudia , Rodriguez Juan M. , Díaz-Castro Francisco , del Campo Andrea , Bravo-Sagua Roberto , Troncoso Rodrigo
Published: May 2022

Glucocorticoids (GC) are steroids hormones that drive circulating glucose availability through gluconeogenesis in the liver. However, alternative splicing of the GR mRNA produces two isoforms, termed GRα and GRβ. GRα is the classic receptor that binds to GCs and mediates the most described actions of GCs. GRβ does not bind GCs and acts as a dominant-negative inhibitor of GRα. Moreover, GRβ has intrinsic and GRα-independent transcriptional activity. To date, it remains unknown if GRβ modulates glucose handling in hepatocytes. Therefore, the study aims to characterize the impact of GRβ overexpression on glucose uptake and storage using an in vitro hepatocyte model. Here we show that GRβ overexpression inhibits the induction of gluconeogenic genes by dexamethasone. Moreover, GRβ activates the Akt pathway, increases glucose transports mRNA, increasing glucose uptake and glycogen storage as an insulin-mimetic. Our results suggest that GRβ has agonist-independent insulin-mimetic actions in HepG2 cells.
Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington’s Disease and Human Blood Plasma
Authors: Ananbeh Hanadi , Novak Jaromir , Juhas Stefan , Juhasova Jana , Klempir Jiri , Doleckova Kristyna , Rysankova Irena , Turnovcova Karolina , Hanus Jaroslav , Hansikova Hana , Vodicka Petr , Kupcova Skalnikova Helena
Published: May 2022

(1) Background: Huntington’s disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients’ plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.
Isolation and Functional Analysis of EPHEMERAL1-LIKE (EPH1L) Genes Involved in Flower Senescence in Cultivated Japanese Gentians
Authors: Takahashi Shigekazu , Yoshida Chiharu , Takahashi Hideyuki , Nishihara Masahiro
Published: May 2022

The elongation of flower longevity increases the commercial value of ornamental plants, and various genes have been identified as influencing flower senescence. Recently, EPHEMERAL1 (EPH1), encoding a NAC-type transcription factor, was identified in Japanese morning glory as a gene that promotes flower senescence. Here we attempted to identify an EPH1 homolog gene from cultivated Japanese gentians and characterized the same with regard to its flower senescence. Two EPH1-LIKE genes (EPH1La and EPH1Lb), considered as alleles, were isolated from a gentian cultivar (Gentiana scabra × G. triflora). Phylogenetic analyses revealed that EPH1L belongs to the NAM subfamily. The transcript levels of EPH1L increased along with its senescence in the field-grown flowers. Under dark-induced senescence conditions, the gentian-detached flowers showed the peak transcription level of EPH1L earlier than that of SAG12, a senescence marker gene, suggesting the involvement of EPH1L in flower senescence. To reveal the EPH1L function, we produced eph1l-knockout mutant lines using the CRISPR/Cas9 system. When the flower longevity was evaluated using the detached flowers as described above, improved longevity was recorded in all genome-edited lines, with delayed induction of SAG12 transcription. The degradation analysis of genomic DNA matched the elongation of flower longevity, cumulatively indicating the involvement of EPH1L in the regulation of flower senescence in gentians.
Collection of End User Requirements and Use Cases during a Pandemic—Towards a Framework for Applied Research Projects
Authors: Scheuer Sabrina , Ferner Pia , Prinzellner Yvonne , Aumayr Georg
Published: May 2022

Research projects in the security domain often aim to develop innovative technology-based solutions for end users (e.g., situational awareness tools, crisis management tools). The pandemic crisis hit hard and without warning, not only influencing our everyday life but also the scientific community. To continue applied research projects during a pandemic, work structures needed to be adapted (e.g., user requirements collection, use case development), as face-to-face events were impossible but crucial to collect high quality requirements with a variety of different stakeholders. To ensure continued multi-stakeholder engagement we developed an overarching framework for collecting user requirements and use cases in an online setting and applied the framework within two research projects. The framework consists of four steps with the aim to assure high quality user requirements and use case collection (first analysis, stakeholder consultation, evaluation and prioritization, technical evaluation). The two projects presented in this paper provide insight on the potential of the framework. The framework offers a structured approach that fits for many different security research projects in terms of the easy application and its transferability. The main advantages (e.g., easily adaptable, reduced workshop time, no need to travel, suitability for different contexts and project types, etc.) and drawbacks (e.g., organization of online events, feedback collection time, etc.) of the framework are presented and discussed in this paper to offer increased stakeholder engagement. Empirical testing of the framework is proposed.
Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF)
Authors: Kaps Leonard , Schleicher Eva Maria , Medina Montano Carolina , Bros Matthias , Gairing Simon Johannes , Ahlbrand Constantin Johannes , Michel Maurice , Klimpke Pascal , Kremer Wolfgang Maximilian , Holtz Stefan , Boedecker-Lips Simone Cosima , Galle Peter Robert , Kraus Daniel , Schattenberg Jörn M. , Labenz Christian , Weinmann-Menke Julia
Published: May 2022

Background: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF. Aim: Our aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward. Methods and results: In this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®. Conclusion: Concentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.
Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes
Authors: Hung Chi-Chih , Yu Pei-Hua , Niu Sheng-Wen , Kuo I-Ching , Lee Jia-Jung , Shen Feng-Ching , Chang Jer-Ming , Hwang Shang-Jyh
Published: May 2022

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes—this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1–5 divided into six groups according to their BMI (between 15 and 35 kg/m2). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5–35 kg/m2) was associated with renal outcomes at CKD stages 1–3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD.
Psychometric Properties of the Wong and Law Emotional Intelligence Scale in a Colombian Manager Sample
Authors: Acosta-Prado Julio César , Zárate-Torres Rodrigo Arturo , Tafur-Mendoza Arnold Alejandro
Published: May 2022

Within the organizational field, emotional intelligence is linked to socially competent behaviors, which allow the development of labor and organizational abilities necessary for professional development. Thus, in workers, emotional intelligence is related to a wide range of organizational variables. The purpose of the present study was to evaluate the psychometric properties of the Wong and Law Emotional Intelligence Scale (WLEIS) in the Colombian context, specifically, in a population of managers. The study was instrumental. The sample consists of 489 Colombian managers, obtained through non-probability sampling (a purposive sample), who work in companies located in Bogota. The results indicated that the four-factor oblique model presents favorable fit indices, as well as the higher-order model, the latter having additional theoretical support. These results indicate that it is possible to consider partial scores for each of the four factors of the WLEIS, as well as an overall emotional-intelligence score. Also, the WLEIS scores have validity evidence based on relations to other variables (convergent and discriminant evidence) and are reliable. These first findings for Colombian managers contribute to the accumulation of international evidence of emotional intelligence measured with the WLEIS.
Ship Path Planning Based on Buoy Offset Historical Trajectory Data
Authors: Zhou Shibo , Wu Zhizheng , Ren Lüzhen
Published: May 2022

In the existing research on the intelligent navigation of ships, navigation route planning often regards light buoys as fixed obstructions. However, due to factors such as water ripples, the position of the buoys keeps periodically changing. If the buoys are set to a fixed range of avoidance areas in the process of ship navigation, it is easy to allow a collision between the ship and the light buoys. Therefore, based on historical motion trajectory data of the buoys, a SARIMA-based time-series prediction model is proposed to estimate the offset position of a given buoy in a specified time. Furthermore, the collision-free path planning approach is presented to dynamically recommend an accurate sailing path. The results of the simulation experiment show that this method can effectively deal with collisions of ships caused by the offset position of the light buoys during the navigation of the large and low-speed autonomous ships.
An Atypical Etiology of Fungal Keratitis Caused by Roussoella neopustulans
Authors: Voidaleski Morgana F. , Queiroz-Telles Flavio , Itikawa Hugo T. , Müller Guilherme G. , Lima Bruna J. F. S. , Trevisoli Lucas E. , Cognialli Regielly C. R. , Crispim Roberta C. L. , Vicente Vania A.
Published: May 2022

Fungal keratitis is caused by a wide spectrum of fungal genera, including molds and yeasts. We report a 42-year-old patient with mycotic keratitis after a direct trauma by a wood fragment. The fungal isolate was identified as Roussoella neopustulans by molecular methods. The treatment with topic natamycin showed progressive improvement of the visual manifestations, and following three months of therapy, the patient regained sight. We report the first case of keratitis associated with R. neopustulans.
Characteristics of the Properties of Absodan Plus Sorbent and Its Ability to Remove Phosphates and Chromates from Aqueous Solutions
Authors: Sočo Eleonora , Domoń Andżelika , Papciak Dorota , Michel Magdalena M. , Cieniek Bogumił , Pająk Dariusz
Published: May 2022

The aim of the research was to characterize the parameters of the diatomite sorbent Absodan Plus as well as to assess its suitability for the adsorption of chromates and phosphates from acidic aqueous solutions simulating the conditions occurring in some types of industrial wastewater. The scope of the research includes XRD, SEM, BET, and PZC analyses, and 3D observation of commercial diatomite granules and batch tests to determine the constants of kinetics and the equilibrium of chromates and phosphates adsorption. Absodan Plus is a diatomite commercial material containing an amorphous phase (33%) and is also the crystalline phase of quartz, hematite, and grossite. The material is macro- and mesoporous and its specific surface area is about 30 m2/g. Its PZC is around pH = 5.5–6.0 and in an acidic environment is able to adsorb the anions. The saturation of the adsorbent surface with molecules of the adsorbed substance occurs after 2 h for chromates and 2.5 h for phosphates. The maximum adsorption capacity of Absodan Plus in terms of phosphorus and chromium amounts to 9.46 mg P/g and 39.1 mg Cr/g, respectively. As shown by XRD analysis, Absodan Plus contains an admixture of hematite, which can support the removal of chromium and phosphorus.
Applications of Subordination Chains and Fractional Integral in Fuzzy Differential Subordinations
Authors: Oros Georgia Irina , Dzitac Simona
Published: May 2022

Fuzzy differential subordination theory represents a generalization of the classical concept of differential subordination which emerged in the recent years as a result of embedding the concept of fuzzy set into geometric function theory. The fractional integral of Gaussian hypergeometric function is defined in this paper and using properties of the subordination chains, new fuzzy differential subordinations are obtained. Dominants of the fuzzy differential subordinations are given and using particular functions as such dominants, interesting geometric properties interpreted as inclusion relations of certain subsets of the complex plane are presented in the corollaries of the original theorems stated. An example is constructed as an application of the newly proved results.
Humic Substances as Microalgal Biostimulants—Implications for Microalgal Biotechnology
Authors: Popa Daria Gabriela , Lupu Carmen , Constantinescu-Aruxandei Diana , Oancea Florin
Published: May 2022

Humic substances (HS) act as biostimulants for terrestrial photosynthetic organisms. Their effects on plants are related to specific HS features: pH and redox buffering activities, (pseudo)emulsifying and surfactant characteristics, capacity to bind metallic ions and to encapsulate labile hydrophobic molecules, ability to adsorb to the wall structures of cells. The specific properties of HS result from the complexity of their supramolecular structure. This structure is more dynamic in aqueous solutions/suspensions than in soil, which enhances the specific characteristics of HS. Therefore, HS effects on microalgae are more pronounced than on terrestrial plants. The reported HS effects on microalgae include increased ionic nutrient availability, improved protection against abiotic stress, including against various chemical pollutants and ionic species of potentially toxic elements, higher accumulation of value-added ingredients, and enhanced bio-flocculation. These HS effects are similar to those on terrestrial plants and could be considered microalgal biostimulant effects. Such biostimulant effects are underutilized in current microalgal biotechnology. This review presents knowledge related to interactions between microalgae and humic substances and analyzes the potential of HS to enhance the productivity and profitability of microalgal biotechnology.
Relationship of the Difficulty of Helicobacter pylori Eradication with Drinking Habits and Allergic Disease
Authors: Ozeki Kayoko , Furuta Takahisa , Hada Kazuhiro , Wakiya Yoshifumi , Ojima Toshiyuki
Published: May 2022

Eradication of Helicobacter pylori (H. pylori) is crucial to reduce the risk of developing gastric ulcers and gastric cancer. Although immunoglobulin E (IgE) levels and alcohol consumption have been shown to influence the failure of H. pylori eradication, the relationship between these factors and the mechanism of failure has not been clarified. Because high IgE levels are associated with eradication failure, the purpose of this study was to clarify the factors leading to high IgE levels. Completed questionnaires and blood test data were collected from patients who visited a university hospital for H. pylori eradication. Logistic regression analysis was per-formed to examine the relationship between high IgE levels and allergic diseases. We also examined the relationship between alcohol intake and high IgE levels. Linear regression analysis was performed on the relationship between the amount of alcohol consumed and IgE measurements. The results showed that patients with allergic diseases and those with high alcohol intake had significantly higher IgE levels. High IgE levels are a risk factor for failure of H. pylori eradication that is associated with drinking habits and alcohol consumption, and our results suggest that daily alcohol consumption should be avoided even in non-allergic patients.
Physiological Importance of Molybdate Transporter Family 1 in Feeding the Molybdenum Cofactor Biosynthesis Pathway in Arabidopsis thaliana
Authors: Minner-Meinen Rieke , Weber Jan-Niklas , Kistner Sarah , Meyfarth Paul , Saudhof Merve , van den Hout Lena , Schulze Jutta , Mendel Ralf-Rainer , Hänsch Robert , Kaufholdt David
Published: May 2022

Molybdate uptake and molybdenum cofactor (Moco) biosynthesis were investigated in detail in the last few decades. The present study critically reviews our present knowledge about eukaryotic molybdate transporters (MOT) and focuses on the model plant Arabidopsis thaliana, complementing it with new experiments, filling missing gaps, and clarifying contradictory results in the literature. Two molybdate transporters, MOT1.1 and MOT1.2, are known in Arabidopsis, but their importance for sufficient molybdate supply to Moco biosynthesis remains unclear. For a better understanding of their physiological functions in molybdate homeostasis, we studied the impact of mot1.1 and mot1.2 knock-out mutants, including a double knock-out on molybdate uptake and Moco-dependent enzyme activity, MOT localisation, and protein–protein interactions. The outcome illustrates different physiological roles for Moco biosynthesis: MOT1.1 is plasma membrane located and its function lies in the efficient absorption of molybdate from soil and its distribution throughout the plant. However, MOT1.1 is not involved in leaf cell imports of molybdate and has no interaction with proteins of the Moco biosynthesis complex. In contrast, the tonoplast-localised transporter MOT1.2 exports molybdate stored in the vacuole and makes it available for re-localisation during senescence. It also supplies the Moco biosynthesis complex with molybdate by direct interaction with molybdenum insertase Cnx1 for controlled and safe sequestering.
Oxidative Stress, Genomic Integrity, and Liver Diseases
Authors: Sadasivam Nanthini , Kim Yu-Ji , Radhakrishnan Kamalakannan , Kim Don-Kyu
Published: May 2022

Excess reactive oxygen species production and free radical formation can lead to oxidative stress that can damage cells, tissues, and organs. Cellular oxidative stress is defined as the imbalance between ROS production and antioxidants. This imbalance can lead to malfunction or structure modification of major cellular molecules such as lipids, proteins, and DNAs. During oxidative stress conditions, DNA and protein structure modifications can lead to various diseases. Various antioxidant-specific gene expression and signal transduction pathways are activated during oxidative stress to maintain homeostasis and to protect organs from oxidative injury and damage. The liver is more vulnerable to oxidative conditions than other organs. Antioxidants, antioxidant-specific enzymes, and the regulation of the antioxidant responsive element (ARE) genes can act against chronic oxidative stress in the liver. ARE-mediated genes can act as the target site for averting/preventing liver diseases caused by oxidative stress. Identification of these ARE genes as markers will enable the early detection of liver diseases caused by oxidative conditions and help develop new therapeutic interventions. This literature review is focused on antioxidant-specific gene expression upon oxidative stress, the factors responsible for hepatic oxidative stress, liver response to redox signaling, oxidative stress and redox signaling in various liver diseases, and future aspects.
Evaluation of Zn2+- and Cu2+-Binding Affinities of Native Cu,Zn-SOD1 and Its G93A Mutant by LC-ICP MS
Authors: Smirnova Julia , Gavrilova Julia , Noormägi Andra , Valmsen Karin , Pupart Hegne , Luo Jinghui , Tõugu Vello , Palumaa Peep
Published: May 2022

The tight binding of Cu and Zn ions to superoxide dismutase 1 (SOD1) maintains the protein stability, associated with amyotrophic lateral sclerosis (ALS). Yet, the quantitative studies remain to be explored for the metal-binding affinity of wild-type SOD1 and its mutants. We have investigated the demetallation of Cu,Zn-SOD1 and its ALS-related G93A mutant in the presence of different standard metal ion chelators at varying temperatures by using an LC-ICP MS-based approach and fast size-exclusion chromatography. Our results showed that from the slow first-order kinetics both metal ions Zn2+ and Cu2+ were released simultaneously from the protein at elevated temperatures. The rate of the release depends on the concentration of chelating ligands but is almost independent of their metal-binding affinities. Similar studies with the G93A mutant of Cu,Zn-SOD1 revealed slightly faster metal-release. The demetallation of Cu,Zn-SOD1 comes always to completion, which hindered the calculation of the KD values. From the Arrhenius plots of the demetallation in the absence of chelators ΔH‡ = 173 kJ/mol for wt and 191 kJ/mol for G93A mutant Cu,Zn-SOD1 was estimated. Obtained high ΔH values are indicative of the occurrence of protein conformational changes before demetallation and we concluded that Cu,Zn-SOD1 complex is in native conditions kinetically inert. The fibrillization of both forms of SOD1 was similar.
Current Hydration Habits: The Disregarded Factor for the Development of Renal and Cardiometabolic Diseases
Authors: Johnson Richard J. , García-Arroyo Fernando E. , Gonzaga-Sánchez Guillermo , Vélez-Orozco Kevin A. , Álvarez-Álvarez Yamnia Quetzal , Aparicio-Trejo Omar Emiliano , Tapia Edilia , Osorio-Alonso Horacio , Andrés-Hernando Ana , Nakagawa Takahiko , Kuwabara Masanari , Kanbay Mehmet , Lanaspa Miguel A. , Sánchez-Lozada Laura Gabriela
Published: May 2022

Improper hydration habits are commonly disregarded as a risk factor for the development of chronic diseases. Consuming an intake of water below recommendations (underhydration) in addition to the substitution of sugar-sweetened beverages (SSB) for water are habits deeply ingrained in several countries. This behavior is due to voluntary and involuntary dehydration; and because young children are exposed to SSB, the preference for a sweet taste is profoundly implanted in the brain. Underhydration and SSB intake lead to mild hyperosmolarity, which stimulates biologic processes, such as the stimulation of vasopressin and the polyol-fructose pathway, which restore osmolarity to normal but at the expense of the continued activation of these biological systems. Unfortunately, chronic activation of the vasopressin and polyol-fructose pathways has been shown to mediate many diseases, such as obesity, diabetes, metabolic syndrome, chronic kidney disease, and cardiovascular disease. It is therefore urgent that we encourage educational and promotional campaigns that promote the evaluation of personal hydration status, a greater intake of potable water, and a reduction or complete halting of the drinking of SSB.
Multimedication in Family Doctor Practices: The German Evidence-Based Guidelines on Multimedication
Authors: Schubert Ingrid , Fessler Joachim , Harder Sebastian , Dinh Truc Sophia , Brueckle Maria-Sophie , Muth Christiane ,   on behalf of the EVITA Study Group
Published: May 2022

Patients with multimorbidity and multimedication require special attention from their treating physicians, as the risks of drug interactions and negative effects on adherence increase with the number of drugs. Most guidelines aim for the treatment of a single disease and do not take potential problems due to multimedication into account. In 2021, updates and evidence-based upgrades of the first version (2012) of the German Guidelines on Multimedication were issued. The aim of the article is to introduce the framework of these evidence-based guidelines, which follows the medication process in six steps: (1) inventory and medication assessment; (2) coordination with the patient; (3) prescription proposal and communication; (4) dispensing of medicines; (5) medication application and self-management; and (6) monitoring. For each step, recommendations and practice tips are presented. The central feature is a structured medication review. The target group is patients with multimorbidity and the concurrent use of five or more drugs. The Medication Appropriateness Index has been modified, and the guiding questions are recommended as guidance for the structured medication review. Overuse and undertreatment are taken into account. The guidelines were consented to in a formal process with 15 medical societies, a patient representative, and experts, as well as piloted in general practices.
IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery
Authors: Jalilian Amir R. , Ocampo-García Blanca , Pasanphan Wanvimol , Sakr Tamer M. , Melendez-Alafort Laura , Grasselli Mariano , Lugao Ademar B. , Yousefnia Hassan , Dispenza Clelia , Janib Siti Mohd , Khan Irfan U. , Maurin Michał , Ulański Piotr , Loo Say Chye Joachim , Safrany Agnes , Osso Joao A. , Duatti Adriano , Katti Kattesh V.
Published: May 2022

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications—all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.
Influence of In Situ Calcium Pectinate Coating on Metoprolol Tartrate Pellets for Controlled Release and Colon-Specific Drug Delivery
Authors: Wanasawas Pimphaka , Mitrevej Ampol , Sinchaipanid Nuttanan
Published: May 2022

In situ calcium pectinate-coated pellets were proposed by applying an alternate coating method to drug-layered pellets to achieve colon-specific drug delivery. Solution layering of metroprolol tartrate, a water-soluble model drug, on inert core pellets was achieved using a centrifugal granulator followed by successive alternate coating with pectin and calcium chloride layers using a fluidized bed bottom spray coater. The effect of the coating sequence on the drug release was studied in phosphate buffer pH 7.4 and 6.0. These test conditions were used to mimic the physiological environments in the distal small intestine and proximal colon, respectively. The results showed that the in situ calcium pectinate layer was successfully generated from the alternate coating of pectin and calcium layers after hydration to form gelation, which was able to control the drug release. The coating sequence played an important role in the drug release. The outermost pectin layer tended to retard the drug release whilst the outermost calcium layer accelerated the release regardless of the number of coating layers. These findings indicate that the release behavior followed the Higuchi model, with the drug release from the coated pellets described by a diffusion control mechanism. It is concluded that the success of the in situ calcium pectinate-coated pellets in controlling the drug release is due to the coating of the outermost layer with pectin and the maintenance of the optimum ratio of calcium to pectin upon hydration.
Microgels Formed by Spontaneous Click Chemistries Utilizing Microfluidic Flow Focusing for Cargo Release in Response to Endogenous or Exogenous Stimuli
Authors: LeValley Paige J. , Parsons Amanda L. , Sutherland Bryan P. , Kiick Kristi L. , Oakey John S. , Kloxin April M.
Published: May 2022

Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local controlled delivery. To address this challenge, degradable hydrogel microparticles, or microgels, loaded with model biocargoes were created with tunable release profiles or triggered burst release using chemistries responsive to endogenous or exogeneous stimuli, respectively. Specifically, microfluidic flow-focusing was utilized to form homogenous microgels with different spontaneous click chemistries that afforded degradation either in response to redox environments for sustained cargo release or light for on-demand cargo release. The resulting microgels were an appropriate size to remain localized within tissues upon injection and were easily passed through a needle relevant for injection, providing means for localized delivery. Release of a model biopolymer was observed over the course of several weeks for redox-responsive formulations or triggered for immediate release from the light-responsive formulation. Overall, we demonstrate the ability of microgels to be formulated with different materials chemistries to achieve various therapeutic release modalities, providing new tools for creation of more complex protein release profiles to improve therapeutic regimens.
Synthesis and Design of Purpurin-18-Loaded Solid Lipid Nanoparticles for Improved Anticancer Efficiency of Photodynamic Therapy
Authors: Yeo Sooho , Song Hyeon Ho , Kim Min Je , Hong Seokhyeon , Yoon Il , Lee Woo Kyoung
Published: May 2022

Purpurin-18 (P18) is one of the essential photosensitizers used in photodynamic therapy (PDT), but its hydrophobicity causes easy coalescence and poor bioavailability. This study aimed to synthesize P18 and design P18-loaded solid lipid nanoparticles (SLNs) to improve its bioavailability. The characteristics of the synthesized P18 and SLNs were evaluated by particle characteristics and release studies. The effects of P18 were evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay as a nonbiological assay and a phototoxicity assay against HeLa and A549 cell lines as a biological assay. The mean particle size and zeta potential of the SLNs were 164.70–762.53 nm and −16.77–25.54 mV, respectively. These results indicate that P18-loaded SLNs are suitable for an enhanced permeability and retention effect as a passive targeting anti-cancer strategy. The formulations exhibited a burst and sustained release based on their stability. The DPBF assay indicated that the PDT effect of P18 improved when it was entrapped in the SLNs. The photocytotoxicity assay indicated that P18-loaded SLNs possessed light cytotoxicity but no dark cytotoxicity. In addition, the PDT activity of the formulations was cell type- and size-dependent. These results suggest that the designed P18-loaded SLNs are a promising tool for anticancer treatment using PDT.
Human–Robot Interaction in Industrial Settings: Perception of Multiple Participants at a Crossroad Intersection Scenario with Different Courtesy Cues
Authors: Alves Carla , Cardoso André , Colim Ana , Bicho Estela , Braga Ana Cristina , Cunha João , Faria Carlos , Rocha Luís A.
Published: May 2022

In environments shared with humans, Autonomous Mobile Robots (AMRs) should be designed with human-aware motion-planning skills. Even when AMRs can effectively avoid humans, only a handful of studies have evaluated the human perception of mobile robots. To establish appropriate non-verbal communication, robot movement should be legible and should consider the human element. In this paper, a study that evaluates humans’ perceptions of different AMR courtesy behaviors at industrial facilities, particularly at crossing areas, is presented. To evaluate the proposed kinesic courtesy cues, we proposed five tests (four proposed cues—stop, deceleration, retreating, and retreating and moving aside—and one control test) with a set of participants taken two by two. We assessed three different metrics, namely, the participants’ self-reported trust in AMR behavior, the legibility of the courtesy cues in the participants’ opinions, and the behavioral analysis of the participants related to each courtesy cue tested. The retreating courtesy cue, regarding the legibility of the AMR behavior, and the decelerate courtesy cue, regarding the behavioral analysis of the participants’ signs of hesitation, are better perceived from the forward view. The results obtained regarding the participants’ self-reported trust showed no significant differences in the two participant perspectives.
Teleoperation Control of an Underactuated Bionic Hand: Comparison between Wearable and Vision-Tracking-Based Methods
Authors: Fu Junling , Poletti Massimiliano , Liu Qingsheng , Iovene Elisa , Su Hang , Ferrigno Giancarlo , De Momi Elena
Published: May 2022

Bionic hands have been employed in a wide range of applications, including prosthetics, robotic grasping, and human–robot interaction. However, considering the underactuated and nonlinear characteristics, as well as the mechanical structure’s backlash, achieving natural and intuitive teleoperation control of an underactuated bionic hand remains a critical issue. In this paper, the teleoperation control of an underactuated bionic hand using wearable and vision-tracking system-based methods is investigated. Firstly, the nonlinear behaviour of the bionic hand is observed and the kinematics model is formulated. Then, the wearable-glove-based and the vision-tracking-based teleoperation control frameworks are implemented, respectively. Furthermore, experiments are conducted to demonstrate the feasibility and performance of these two methods in terms of accuracy in both static and dynamic scenarios. Finally, a user study and demonstration experiments are conducted to verify the performance of these two approaches in grasp tasks. Both developed systems proved to be exploitable in both powered and precise grasp tasks using the underactuated bionic hand, with a success rate of 98.6% and 96.5%, respectively. The glove-based method turned out to be more accurate and better performing than the vision-based one, but also less comfortable, requiring greater effort by the user. By further incorporating a robot manipulator, the system can be utilised to perform grasp, delivery, or handover tasks in daily, risky, and infectious scenarios.
Evaluation of FY-4A Temperature Profile Products and Application to Winter Precipitation Type Diagnosis in Southern China
Authors: Gao Yang , Mao Dongyan , Wang Xin , Qin Danyu
Published: May 2022

FY-4A GIIRS temperature profile products have provided unprecedented information for studying the atmospheric characteristics of thermal structures since 2020. The main objective of this paper is to evaluate GIIRS temperature profile products by using radiosonde observations and then apply them to the diagnosis of winter precipitation types in southern China. GIIRS temperature profile products for four types (clear sky perfect quality, cloudy sky perfect quality, cloudy sky good quality and cloudy sky bad quality) show different performances. Relatively, the cloud can affect the quality and quantity of GIIRS products. At different pressure levels, the perfect flagged data under the clear or cloudy sky show the best agreement with radiosonde observations, yielding the highest Pearson correlation coefficient and lowest mean bias as well as root mean square error. The good flagged data have a slight deviation from the perfect data. The impact on the quantity of the GIIRS temperature data is greater than that on the quality with an increase in cloud top height. A case investigation was carried out to analyze the performance of GIIRS temperature profiles for the diagnosis of precipitation types in a winter storm of 2022. The GIIRS temperature profiles represent the reasonable atmospheric thermal structures in the rain and snow in Hubei and Hunan provinces. The GIIRS temperature below 700 hPa is an important indictor to precipitation type diagnosis. Furthermore, two critical thresholds for GIIRS temperatures, which are below −2 °C at 850 hPa and below 0 °C at 925 hPa, respectively, are proposed for the occurrence of snowfall in this winter storm. In addition, the distribution of GIIRS temperature at different pressure levels is consistent with radiosonde observations in a freezing rain event in Guiyang, all of which show the warm rain mechanism by combining the cloud top information.
Efficient Shallow Network for River Ice Segmentation
Authors: Sola Daniel , Scott K. Andrea
Published: May 2022

River ice segmentation, used for surface ice concentration estimation, is important for validating river processes and ice-formation models, predicting ice jam and flooding risks, and managing water supply and hydroelectric power generation. Furthermore, discriminating between anchor ice and frazil ice is an important factor in understanding sediment transport and release events. Modern deep learning techniques have proved to deliver promising results; however, they can show poor generalization ability and can be inefficient when hardware and computing power is limited. As river ice images are often collected in remote locations by unmanned aerial vehicles with limited computation power, we explore the performance-latency trade-offs for river ice segmentation. We propose a novel convolution block inspired by both depthwise separable convolutions and local binary convolutions giving additional efficiency and parameter savings. Our novel convolution block is used in a shallow architecture which has 99.9% fewer trainable parameters, 99% fewer multiply–add operations, and 69.8% less memory usage than a UNet, while achieving virtually the same segmentation performance. We find that the this network trains fast and is able to achieve high segmentation performance early in training due to an emphasis on both pixel intensity and texture. When compared to very efficient segmentation networks such as LR-ASPP with a MobileNetV3 backbone, we achieve good performance (mIoU of 64) 91% faster during training on a CPU and an overall mIoU that is 7.7% higher. We also find that our network is able to generalize better to new domains such as snowy environments.
Massive MIMO Indoor Transmissions at 38 and 65 GHz Applying Novel HBF Techniques for 5G
Authors: Sanchis-Borrás Concepción , Martinez-Ingles Maria-Teresa , Molina-Garcia-Pardo Jose-Maria
Published: May 2022

The 5G Infrastructure Public Private Partnership (5GPPP) has recently published a white paper about 5G service indoors, since up to now, it had mainly focused on the outdoors. In an indoor environment, the requirements are different since the propagation mechanism differs from other scenarios. Furthermore, previous works have shown that space frequency block code (SFBC) techniques applied to multiple antennas improve performance compared to single-input single-output (SISO) systems. This paper presents an experimental study in an indoor environment regarding the performance of a massive multiple-input multiple-output (mMIMO) millimeter-wave (mmWave) system based on the 5G New Radio (NR) standard in two frequency bands. In a first step, the 38 and 65 GHz bands are compared by applying a low-complexity hybrid beamforming (HBF) algorithm. In a second step, the throughput and the maximum achievable distance are studied using a new algorithm that combines the SFBC technique and HBF. Results show, at 38 GHz with HBF and aggregated bandwidths (4 × 100 MHz), a maximum throughput of 4.30 Gbit/s up to 4.1 m. At 65 GHz, the SFBC + HBF algorithm improves the communication distance by 1.34, 1.61, or 1.75 m for bandwidths of 100, 200, or 400 MHz, respectively.