bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring dissolution profiles of single controlled-release drug pellets
Authors: Bhakta Heran C. , Lin Jessica M. , Grover William H. 
Published: November 2020

AbstractMany solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only “snapshots” of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry.
A birdstrike risk assessment model and its application at Ordos Airport, China
Authors: Hu Yuanyuan , Xing Pu , Yang Fan , Feng Gang , Yang Guisheng , Zhang Zhengwang 
Published: November 2020

AbstractBirdstrikes are an important threat to aviation safety. A standardized, scientific process for assessing birdstrike risk could prevent accidents, thereby improving the flight safety and reducing economic losses. However, China currently lacks a unified birdstrike risk assessment system. Here, we propose and validate a new model for assessing birdstrike risk in order to fill that need. The model consists of two elements. First, empirical data are collected on the occurrence of birds at the airport and in a surrounding 8 km buffer. Second, each species is evaluated with a risk assessment matrix that takes into account the number of birds, weight, flight altitude, a tendency to cluster, and range of activity. These five factors allow each species to be divided into one of three risk levels: high danger (level 3), moderate danger (level 2) and low danger (level 1). We propose corresponding birdstrike prevention measures for each level. We apply this method to the civil aviation airport in Ordos, China. We found that 20 of the 118 species of birds in and around the airport were high danger birds (level 3). To validate this process, we compared these species with records of birdstrike accidents in a database maintained by the Civil Aviation Administration of China (CAAC) for 2007–2016. We found that 42% of the species we identified as high risk had been involved in at least one birdstrike accident, and that the remaining 58% belonged to families that appeared in the database. The high degree of overlap gives us high confidence in the practicality of our risk assessment model, which is based on the risk management concept of ISO 31000. Critically, this new model and method for predicting bird strike risk can be replicated at other airports around the world, even where no extensive records have been kept of past birdstrikes.
Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology
Authors: Nepotchatykh Evguenia , Elremaly Wesam , Caraus Iurie , Godbout Christian , Leveau Corinne , Chalder Lynda , Beaudin Catherine , Kanamaru Emi , Kosovskaia Renata , Lauzon Shawn , Maillet Yanick , Franco Anita , Lascau-Coman Viorica , Bouhanik Saadallah , Gaitan Yaned Patricia , Li Dawei , Moreau Alain 
Published: November 2020

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease, rooted in multi-system dysfunctions characterized by unexplained debilitating fatigue. Post-exertional malaise (PEM), defined as the exacerbation of the patient's symptoms following minimal physical or mental stress, is a hallmark of ME/CFS. While multiple case definitions exist, there is currently no well-established biomarkers or laboratory tests to diagnose ME/CFS. Our study aimed to investigate circulating microRNA expression in severely ill ME/CFS patients before and after an innovative stress challenge that stimulates PEM. Our findings highlight the differential expression of eleven microRNAs associated with a physiological response to PEM. The present study uncovers specific microRNA expression signatures associated with ME/CFS in response to PEM induction and reports microRNA expression patterns associated to specific symptom severities. The identification of distinctive microRNA expression signatures for ME/CFS through a provocation challenge is essential for the elucidation of the ME/CFS pathophysiology, and lead to accurate diagnoses, prevention measures, and effective treatment options.
Human pericentromeric tandemly repeated DNA is transcribed at the end of oocyte maturation and is associated with membraneless mitochondria-associated structures
Authors: Dobrynin M. A. , Korchagina N. M. , Prjibelski A. D. , Shafranskaya D. , Ostromyshenskii D. I. , Shunkina K. , Stepanova I. , Kotova A. V. , Podgornaya O. I. , Enukashvily N. I. 
Published: November 2020

AbstractMost of the human genome is non-coding. However, some of the non-coding part is transcriptionally active. In humans, the tandemly repeated (TR) pericentromeric non-coding DNA—human satellites 2 and 3 (HS2, HS3)—are transcribed in somatic cells. These transcripts are also found in pre- and post-implantation embryos. The aim of this study was to analyze HS2/HS3 transcription and cellular localization of transcripts in human maturating oocytes. The maternal HS2/HS3 TR transcripts transcribed from both strands were accumulated in the ooplasm in GV-MI oocytes as shown by DNA–RNA FISH (fluorescence in-situ hybridization). The transcripts’ content was higher in GV oocytes than in somatic cumulus cells according to real-time PCR. Using bioinformatics analysis, we demonstrated the presence of polyadenylated HS2 and HS3 RNAs in datasets of GV and MII oocyte transcriptomes. The transcripts shared a high degree of homology with HS2, HS3 transcripts previously observed in cancer cells. The HS2/HS3 transcripts were revealed by a combination of FISH and immunocytochemical staining within membraneless RNP structures that contained DEAD-box helicases DDX5 and DDX4. The RNP structures were closely associated with mitochondria, and are therefore similar to membraneless bodies described previously only in oogonia. These membraneless structures may be a site for spatial sequestration of RNAs and proteins in both maturating oocytes and cancer cells.
Alterations in detrusor contractility in rat model of bladder cancer
Authors: Philyppov Igor B. , Sotkis Ganna V. , Rock Aurelien , Roudbaraki Morad , Bonnal Jean-Louis , Mauroy Brigitte , Prevarskaya Natalia , Shuba Yaroslav M. 
Published: November 2020

AbstractUrinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.
Hemocytes released in seawater act as Trojan horses for spreading of bacterial infections in mussels
Authors: Caza France , Bernet Eve , Veyrier Frédéric J. , Betoulle Stéphane , St-Pierre Yves 
Published: November 2020

AbstractGlobal warming has been associated with increased episodes of mass mortality events in invertebrates, most notably in bivalves. Although the spread of pathogens is one of multiple factors that contribute to such mass mortality events, we don’t fully understand the pathophysiological consequences of sea warming on invertebrates. In this work, we show that in temperature stress conditions, circulating hemocytes in mussels leave the hemolymph to gain access to the intervalvar fluid before being released in seawater. External hemocytes can survive for several hours in seawater before entering other mussels. When infected by bacteria, externally-infected hemocytes can enter naive mussels and promote bacterial dissemination in the host. These results reveal the existence of a new opportunistic mechanism used by pathogens to disseminate in marine ecosystems. Such mechanisms may explain how thermal anomalies triggered by global warming can favor episodic mass mortality observed in recent years in marine ecosystem.
Rifting of the oceanic Azores Plateau with episodic volcanic activity
Authors: Storch B. , Haase K. M. , Romer R. H. W. , Beier C. , Koppers A. A. P. 
Published: November 2020

AbstractExtension of the Azores Plateau along the Terceira Rift exposes a lava sequence on the steep northern flank of the Hirondelle Basin. Unlike typical tholeiitic basalts of oceanic plateaus, the 1.2 km vertical submarine stratigraphic profile reveals two successive compositionally distinct basanitic to alkali basaltic eruptive units. The lower unit is volumetrically more extensive with ~ 1060 m of the crustal profile forming between ~ 2.02 and ~ 1.66 Ma, followed by a second unit erupting the uppermost ~ 30 m of lavas in ~ 100 kyrs. The age of ~ 1.56 Ma of the youngest in-situ sample at the top of the profile implies that the 35 km-wide Hirondelle Basin opened after this time along normal faults. This rifting phase was followed by alkaline volcanism at D. João de Castro seamount in the basin center indicating episodic volcanic activity along the Terceira Rift. The mantle source compositions of the two lava units change towards less radiogenic Nd, Hf, and Pb isotope ratios. A change to less SiO2-undersaturated magmas may indicate increasing degrees of partial melting beneath D. João de Castro seamount, possibly caused by lithospheric thinning within the past 1.5 million years. Our results suggest that rifting of oceanic lithosphere alternates between magmatically and tectonically dominated phases.
Diversity in susceptibility reactions of winter wheat genotypes to obligate pathogens under fluctuating climatic conditions
Authors: Jevtić Radivoje , Župunski Vesna , Lalošević Mirjana , Jocković Bojan , Orbović Branka , Ilin Sonja 
Published: November 2020

AbstractTo date, studies have usually focused on the impact of abiotic factors on the distribution of plant pathogens and have built forecast models for the prediction of pathogen outbreaks. However, the impact of the combined effects of biotic and abiotic factors on the prevalence of economically important pathogens has usually been neglected. The objective of this study was to determine the relationship between powdery mildew and rusts of wheat and to examine how the combined effects of abiotic and biotic factors influence their prevalence. The study was conducted in the period 2016–2019 using the collection of 2158 genotypes of winter wheat. The most influential factors on disease indices and relationships among obligate pathogens were determined using multiple regression models and principal component analysis. The possibility of the coexistence of different rust species in the same growing season and in the same field was shown. The significant influence of fluctuations in winter temperatures on changes in the prevalence of obligate pathogens was determined. The strong impact of genotypes and their reaction on climatic elements in certain phenological stages were shown to be significant factors influencing the interactions among obligate pathogens and the predominance of one pathogen over another.
Cardioprotective effects of short-term empagliflozin treatment in db/db mice
Authors: Radlinger Bernhard , Hornsteiner Florian , Folie Sabrina , Salvenmoser Willi , Haubner Bernhard J. , Schuetz Thomas , Haas Simone , Ress Claudia , Adolph Timon E. , Salzmann Karin , Weiss Bernhard , Tilg Herbert , Kaser Susanne 
Published: November 2020

AbstractSodium glucose transporter (SGLT)-2 inhibitors have consistently shown cardioprotective effects independent of the glycemic status of treated patients. In this study we aimed to investigate underlying mechanisms of short-term empagliflozin treatment in a mouse model of type II diabetes. Male db/db mice were fed a western type diet with or without enrichment with empagliflozin for 7 days. While glucose tolerance was significantly improved in empagliflozin treated mice, body weight and fasting insulin levels were comparable in both groups. Cardiac insulin signaling activity indicated by reduced proteinkinase B (AKT) phosphorylation was significantly decreased in the empagliflozin treated group. Remarkably, mitochondrial mass estimated by citrate synthase activity was significantly elevated in empagliflozin treated mice. Accordingly, mitochondrial morphology was significantly altered upon treatment with empagliflozin as analysed by transmission electron microscopy. Additionally, short-term empagliflozin therapy was associated with a changed cardiac tissue cytokine expression in favor of an anti-inflammatory pattern. Our data suggest that early cardioprotection in empagliflozin treated mice is independent of a reduction in body weight or hyperinsulinemia. Ameliorated mitochondrial ultrastructure, attenuated cardiac insulin signaling and diminished cardiac inflammation might contribute to the cardioprotective effects of empagliflozin.
GMStool: GWAS-based marker selection tool for genomic prediction from genomic data
Authors: Jeong Seongmun , Kim Jae-Yoon , Kim Namshin 
Published: November 2020

AbstractThe increased accessibility to genomic data in recent years has laid the foundation for studies to predict various phenotypes of organisms based on the genome. Genomic prediction collectively refers to these studies, and it estimates an individual’s phenotypes mainly using single nucleotide polymorphism markers. Typically, the accuracy of these genomic prediction studies is highly dependent on the markers used; however, in practice, choosing optimal markers with high accuracy for the phenotype to be used is a challenging task. Therefore, we present a new tool called GMStool for selecting optimal marker sets and predicting quantitative phenotypes. The GMStool is based on a genome-wide association study (GWAS) and heuristically searches for optimal markers using statistical and machine-learning methods. The GMStool performs the genomic prediction using statistical and machine/deep-learning models and presents the best prediction model with the optimal marker-set. For the evaluation, the GMStool was tested on real datasets with four phenotypes. The prediction results showed higher performance than using the entire markers or the GWAS-top markers, which have been used frequently in prediction studies. Although the GMStool has several limitations, it is expected to contribute to various studies for predicting quantitative phenotypes. The GMStool written in R is available at www.github.com/JaeYoonKim72/GMStool.
Possible contribution of sialic acid to the enhanced tumor targeting efficiency of nanoparticles engineered with doxorubicin
Authors: Lee Song Yi , Nam Suyeong , Koo Ja Seong , Kim Sungyun , Yang Mingyu , Jeong Da In , Hwang ChaeRim , Park JiHye , Cho Hyun-Jong 
Published: November 2020

AbstractDoxorubicin (DOX)-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) including phloretin (PHL) were designed and the feasible contribution of sialic acid (SA) to the improved tumor targeting and penetration capabilities was elucidated in lung adenocarcinoma models. DOX has been clinically used as liposomal formulations after its introduction to the inner side of vehicles, however DOX is anchored in the outer surface of PLGA NPs for improved tumor penetration by interactions with SA in this study. DOX (positively charged at physiological pH) was adsorbed onto the negatively charged PLGA NPs via electrostatic interactions and consequent binding of SA (negatively charged at physiological pH) to DOX located in NPs was also elucidated. DOX layer in DOX@PLGA NPs rendered improved endocytosis and partial contribution of SA (expressed in cancer cells) to that endocytosis was demonstrated. DOX@PLGA/PHL NPs provided enhanced antiproliferation potentials in A549 cells rather than single agent (DOX or PHL)-installed NPs. In addition, DOX-SA interactions seemed to play critical roles in tumor infiltration and accumulation of DOX@PLGA NPs in A549 tumor-xenografted mouse model. All these findings support the novel use of DOX which is used for the surface engineering of NPs for improved tumor targeting and penetration.
The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Authors: Arcanjo Angélica , Logullo Jorgete , Menezes Camilla Cristie Barreto , de Souza Carvalho Giangiarulo Thais Chrispim , dos Reis Mirella Carneiro , de Castro Gabriellen Menezes Migliani , da Silva Fontes Yasmin , Todeschini Adriane Regina , Freire-de-Lima Leonardo , Decoté-Ricardo Debora , Ferreira-Pereira Antônio , Freire-de-Lima Celio Geraldo , Barroso Shana Priscila Coutinho , Takiya Christina , Conceição-Silva Fátima , Savino Wilson , Morrot Alexandre 
Published: November 2020

AbstractThe novel coronavirus SARS-CoV-2 causes COVID-19, a highly pathogenic viral infection threatening millions. The majority of the individuals infected are asymptomatic or mildly symptomatic showing typical clinical signs of common cold. However, approximately 20% of the patients can progress to acute respiratory distress syndrome (ARDS), evolving to death in about 5% of cases. Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues. This systemic infection is associated with higher neutrophil to lymphocyte ratio in infected tissues and high levels of pro-inflammatory cytokines leading to an extensive microthrombus formation with multiorgan failure. Herein we investigated whether SARS-CoV-2 can stimulate extracellular neutrophils traps (NETs) in a process called NETosis. We demonstrated for the first time that SARS-CoV-2 in fact is able to activate NETosis in human neutrophils. Our findings indicated that this process is associated with increased levels of intracellular Reactive Oxygen Species (ROS) in neutrophils. The ROS-NET pathway plays a role in thrombosis formation and our study suggest the importance of this target for therapy approaches against disease.
Involvement of 8-O-acetylharpagide for Ajuga taiwanensis mediated suppression of senescent phenotypes in human dermal fibroblasts
Authors: Hsu Wei-Hsiang , Lin Bing-Ze , Leu Jyh-Der , Lo Pin-Ho , Yu Hsueh-Yen , Chen Chao-Tsung , Tu Yuan-Heng , Lin Yun-Lian , Lee Yi-Jang 
Published: November 2020

Abstract
Herbal medicines are attractive agents for human care. In this study, we found that the alcohol extract of Ajuga taiwanensis (ATE) screened from a chemical bank exhibited potent capacity for suppressing senescence associated biomarkers, including SA-β-gal and up-regulated p53 in old human dermal fibroblasts (HDFs) without induction of significant cytotoxicity up to 100 µg/ml. Concomitantly, cells re-entered the cell cycle by reducing G1 phase arrest and increasing cell growth rate. The ATE was further partitioned to obtain the sub-fractions of n-butanol (BuOH), ethyl acetate (EA) and water. The BuOH and water sub-fractions exhibited less effects on prohibition of cell growth than the EA sub-fraction. All of these sub-fractions exhibited the ability on suppressing SA-β-gal and p53 of old HDFs as low as 5–10 µg/ml. Under the activity guided fractionation and isolation, a major active constituent named AT-1 was isolated. The AT-1 was further identified as 8-O-acetylharpagide by structural analysis, and it could suppress SA-β-gal and p53 of old HDFs below 10 µM. In addition, the intracellular reactive oxygen species (ROS) levels of old HDFs were suppressed by ATE, the sub-fractions of BuOH and water, and AT-1. However, the EA sub-fraction showed little ability on suppression of ROS. Furthermore, we performed an in vivo study using aging mice to be fed with ATE and the sub-fractions followed by immunohistochemical (IHC) staining. The expression of p53 and SA-β-gal was significantly reduced in several tissue sections, including skin, liver, kidney, and spleen. Taken together, current data demonstrated that A. taiwanensis could suppress cellular senescence in HDFs, and might be used for health care.