bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Specific Inhibitors for Oncogenic Phosphatase PPM1D by Using Ion-Responsive DNA Aptamer Library
Authors: Kaneko Atsushi , Watari Miyuu , Mizunuma Masataka , Saito Hikaru , Furukawa Kazuhiro , Chuman Yoshiro
Published: October 2020

(1) Background: Ser/Thr protein phosphatase PPM1D is an oncogenic protein. In normal cells, however, PPM1D plays essential roles in spermatogenesis and immune response. Hence, it is necessary to develop novel PPM1D inhibitors without side effects on normal cells. Stimuli-responsive molecules are suitable for the spatiotemporal regulation of inhibitory activity. (2) Methods: In this study, we designed an ion-responsive DNA aptamer library based on G-quadruplex DNA that can change its conformation and function in response to monovalent cations. (3) Results: Using this library, we identified the PPM1D specific inhibitor M1D-Q5F aptamer. The M1D-Q5F aptamer showed anti-cancer activity against breast cancer MCF7 cells. Interestingly, the induction of the structural change resulting in the formation of G-quadruplex upon stimulation by monovalent cations led to the enhancement of the inhibitory activity and binding affinity of M1D-Q5F. (4) Conclusions: These data suggest that the M1D-Q5F aptamer may act as a novel stimuli-responsive anti-cancer agent.
Effectiveness of Autologous Platelet Concentrates in Management of Young Immature Necrotic Permanent Teeth—A Systematic Review and Meta-Analysis
Authors: Panda Saurav , Mishra Lora , Arbildo-Vega Heber Isac , Lapinska Barbara , Lukomska-Szymanska Monika , Khijmatgar Shahnawaz , Parolia Abhishek , Bucchi Cristina , Fabbro Massimo Del
Published: October 2020

The use of autologous platelet concentrates (APCs) in regenerative endodontic procedures is inconsistent and unclear. The aim of this meta-analysis was to evaluate the effectiveness of autologous platelet concentrates compared to traditional blood-clot regeneration for the management of young, immature, necrotic, permanent teeth. The digital databases MEDLINE, SCOPUS, CENTRAL, Web of Science, and EMBASE were searched to identify ten randomized clinical trials. The outcomes at postoperative follow-up, such as dentinal wall thickness (DWT), increase in root length (RL), calcific barrier formation (CB), apical closure (AC), vitality response (VR), and success rate (SR), were subjected to both qualitative synthesis and quantitative meta-analysis. The meta-analysis showed that APCs significantly improved apical closure (risk ratio (RR) = 1.17; 95% CI: 1.01, 1.37; p = 0.04) and response to vitality pulp tests (RR = 1.61; 95% CI: 1.03, 2.52; p = 0.04), whereas no significant effect was observed on root lengthening, dentin wall thickness, or success rate of immature, necrotic teeth treated with regenerative endodontics. APCs could be beneficial when treating young, immature, necrotic, permanent teeth regarding better apical closure and improved response to vitality tests.
Involvement of Actin and Actin-Binding Proteins in Carcinogenesis
Authors: Izdebska Magdalena , Zielińska Wioletta , Hałas-Wiśniewska Marta , Grzanka Alina
Published: October 2020

The actin cytoskeleton plays a crucial role in many cellular processes while its reorganization is important in maintaining cell homeostasis. However, in the case of cancer cells, actin and ABPs (actin-binding proteins) are involved in all stages of carcinogenesis. Literature has reported that ABPs such as SATB1 (special AT-rich binding protein 1), WASP (Wiskott-Aldrich syndrome protein), nesprin, and villin take part in the initial step of carcinogenesis by regulating oncogene expression. Additionally, changes in actin localization promote cell proliferation by inhibiting apoptosis (SATB1). In turn, migration and invasion of cancer cells are based on the formation of actin-rich protrusions (Arp2/3 complex, filamin A, fascin, α-actinin, and cofilin). Importantly, more and more scientists suggest that microfilaments together with the associated proteins mediate tumor vascularization. Hence, the presented article aims to summarize literature reports in the context of the potential role of actin and ABPs in all steps of carcinogenesis.
Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation
Authors: Ruane Peter T. , Tan Cheryl M. J. , Adlam Daman J. , Kimber Susan J. , Brison Daniel R. , Aplin John D. , Westwood Melissa
Published: October 2020

Embryo implantation begins with blastocyst trophectoderm (TE) attachment to the endometrial epithelium, followed by the breaching of this barrier by TE-derived trophoblast. Dynamic protein modification with O-linked β-N-acetylglucosamine (O-GlcNAcylation) is mediated by O-GlcNAc transferase and O-GlcNAcase (OGA), and couples cellular metabolism to stress adaptation. O-GlcNAcylation is essential for blastocyst formation, but whether there is a role for this system at implantation remains unexplored. Here, we used OGA inhibitor thiamet g (TMG) to induce raised levels of O-GlcNAcylation in mouse blastocysts and human trophoblast cells. In an in vitro embryo implantation model, TMG promoted mouse blastocyst breaching of the endometrial epithelium. TMG reduced expression of TE transcription factors Cdx2, Gata2 and Gata3, suggesting that O-GlcNAcylation stimulated TE differentiation to invasive trophoblast. TMG upregulated transcription factors OVOL1 and GCM1, and cell fusion gene ERVFRD1, in a cell line model of syncytiotrophoblast differentiation from human TE at implantation. Therefore O-GlcNAcylation is a conserved pathway capable of driving trophoblast differentiation. TE and trophoblast are sensitive to physical, chemical and nutritive stress, which can occur as a consequence of maternal pathophysiology or during assisted reproduction, and may lead to adverse neonatal outcomes and associated adult health risks. Further investigation of how O-GlcNAcylation regulates trophoblast populations arising at implantation is required to understand how peri-implantation stress affects reproductive outcomes.
Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings
Authors: Schwartz Brian E. , Rajagopal Vaishnavi , Smith Cynthia , Cohick Evan , Whissell Gavin , Gamboa Mario , Pai Rutuja , Sigova Alla , Grossman Iris , Bumcrot David , Sasidharan Kavitha , Romeo Stefano , Sehgal Alfica , Pingitore Piero
Published: October 2020

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging worldwide epidemics, projected to become the leading cause of liver transplants. The strongest genetic risk factor for NAFLD/NASH susceptibility and progression is a single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), rs738409, encoding the missense mutation I148M. This aminoacidic substitution interferes with the normal remodeling of lipid droplets in hepatocytes. It is also thought to play a key role in promoting liver fibrosis by inhibiting the release of retinol from hepatic stellate cells. Reducing PNPLA3 levels in individuals homozygous for 148M may be an effective treatment for the entire spectrum of NAFLD, based on gene dosage analysis in the human population, as well as the protective effect of another naturally occurring SNP (rs2294918) in PNPLA3 which, when co-inherited, reduces PNPLA3 mRNA levels to 50% and counteracts disease risk. By screening a clinical compound library targeting specific signaling pathways active in primary human hepatocytes, we identified momelotinib, a drug evaluated in clinical trials to treat myelofibrosis, as a potent down-regulator of PNPLA3 expression, across all genotypes. We found that momelotinib treatment yielded >80% reduction in PNPLA3 mRNA in human primary hepatocytes and stellate cells, as well as in vivo via acute and chronic treatment of WT mice. Using a human multilineage 3D spheroid model of NASH homozygous for the PNPLA3 mutant protein, we additionally show that it decreases PNPLA3 mRNA as well as intracellular lipid content. Furthermore, we show that the effects on PNPLA3 coincide with changes in chromatin accessibility within regulatory regions of the PNPLA3 locus, consistent with inhibition occurring at the level of transcription. In addition to its primary reported targets, the JAK kinases, momelotinib inhibits several non-JAK kinases, including ACVR1. Using a combination of targeted siRNA knockdowns and signaling pathway perturbations, we show that momelotinib reduces the expression of the PNPLA3 gene largely through the inhibition of BMP signaling rather than the JAK/STAT pathway. Overall, our work identified momelotinib as a potential NASH therapeutic and uncovered previously unrecognized connections between signaling pathways and PNPLA3. These pathways may be exploited by drug modalities to “tune down” the level of gene expression, and therefore offer a potential therapeutic benefit to a high at-risk subset of NAFLD/NASH patients.
Chitosan, Nisin, Silicon Dioxide Nanoparticles Coating Films Effects on Blueberry (Vaccinium myrtillus) Quality
Authors: Eldib Rok , Khojah Ebtihal , Elhakem Abeer , Benajiba Nada , Helal Mahmoud
Published: October 2020

Chitosan coating plus silicon dioxide nanoparticles and nisin were applied on fresh blueberry samples in order to find out safety packaging assay during the post-harvest process. Studies were performed in-vitro for fruit quality as physicochemical parameters and oxidation, while microbiological analyses as molds/yeast and mesophilics populations were examined in-vivo. The selected silicon dioxide nanoparticles 1% and nisin 1%, were added into a chitosan solution, which resulted in four groups of coated blueberries. After storage at ambient temperature, fruits were examined for two, four, six, and eight days. It was noticed that the hardness, chewiness, and cohesiveness of all blueberry samples were increased during the storage. Chitosan-nano-silicon dioxide (CHN-Nano) and (CHN-N-Nano) with the addition of nisin helped to control shrinking (38.52%) and decay rates (8.61%). Moreover, (CHN-N-Nano) reported the lowest L* values (10.54) for the color index, and inhibited the microbial populations (3.60 and 2.73 log CFU/g) for molds/yeast and mesophilics, respectively. (CHN-Nano) reported the lowest value for ph (2.61) and the highest for anthocyanin content (75.19 cyanidin-3-glucoside mg/100 g). The chitosan coating substantially maintained Vitamin C (7.34 mg/100 g) and polyphenoloxidase (PPO) (558.03 U min−1·g−1). The results suggest that nano-material with chitosan film coatings that contained nisin were effective for fresh blueberry preservation under ambient temperature.
New Mobile Device to Measure Verticality Perception: Results in Young Subjects with Headaches
Authors: Rodríguez-Almagro Daniel , Obrero-Gaitán Esteban , Lomas-Vega Rafael , Zagalaz-Anula Noelia , Osuna-Pérez María Catalina , Achalandabaso-Ochoa Alexander
Published: October 2020

The subjective visual vertical (SVV) test has been frequently used to measure vestibular contribution to the perception of verticality. Recently, mobile devices have been used to efficiently perform this measurement. The aim of this study was to analyze the perception of verticality in subjects with migraines and headaches. A cross-sectional study was conducted that included 28 patients with migraine, 74 with tension-type headache (TTH), and 93 healthy subjects. The SVV test was used through a new virtual reality system. The mean absolute error (MAE) of degrees deviation was also measured to qualify subjects as positive when it was greater than 2.5°. No differences in the prevalence of misperception in verticality was found among healthy subjects (31.18%), migraineurs (21.43%), or those with TTH (33.78%) (p = 0.480). The MAE was not significantly different between the three groups (migraine = 1.36°, TTH = 1.61°, and healthy = 1.68°) (F = 1.097, p = 0.336, and η2 = 0.011). The perception of verticality could not be explained by any variable usually related to headaches. No significant differences exist in the vestibular contribution to the perception of verticality between patients with headaches and healthy subjects. New tests measuring visual and somatosensory contribution should be used to analyze the link between the perception of verticality and headaches.
HIL-Assessed Fast and Accurate Single-Phase Power Calculation Algorithm for Voltage Source Inverters Supplying to High Total Demand Distortion Nonlinear Loads
Authors: El Mariachet Jorge , Guan Yajuan , Matas Jose , Martín Helena , Li Mingshen , Guerrero Josep M.
Published: October 2020

The dynamic performance of the local control of single-phase voltage source inverters (VSIs) can be degraded when supplying to nonlinear loads (NLLs) in microgrids. When this control is based on the droop principles, a proper calculation of the active and reactive averaged powers (P–Q) is essential for a proficient dynamic response against abrupt NLL changes. In this work, a VSI supplying to an NLL was studied, focusing the attention on the P–Q calculation stage. This stage first generated the direct and in-quadrature signals from the measured load current through a second-order generalized integrator (SOGI). Then, the instantaneous power quantities were obtained by multiplying each filtered current by the output voltage, and filtered later by utilizing a SOGI to acquire the averaged P–Q parameters. The proposed algorithm was compared with previous proposals, while keeping the active power steady-state ripple constant, which resulted in a faster calculation of the averaged active power. In this case, the steady-state averaged reactive power presented less ripple than the best proposal to which it was compared. When reducing the velocity of the proposed algorithm for the active power, it also showed a reduction in its steady-state ripple. Simulations, hardware-in-the-loop, and experimental tests were carried out to verify the effectiveness of the proposal.
A Temperature-Risk and Energy-Saving Evaluation Model for Supporting Energy-Saving Measures for Data Center Server Rooms
Authors: Sasakura Kosuke , Aoki Takeshi , Komatsu Masayoshi , Watanabe Takeshi
Published: October 2020

As data centers have become increasingly important in recent years their operational management must attain higher efficiency and reliability. Moreover, the power consumption of a data center is extremely large, and it is anticipated that it will continue to increase, so energy saving has become an urgent issue concerning data centers. In the meantime, the environment of the server rooms in data centers has become complicated owing to the introduction of virtualization technology, the installation of high-heat density information and communication technology (ICT) equipment and racks, and the diversification of cooling methods. It is very difficult to manage a server room in the case of such a complicated environment. When energy-saving measures are implemented in a server room with such a complicated environment, it is important to evaluate “temperature risks” in advance and calculate the energy-saving effect after the measures are taken. Under those circumstances, in this study, two prediction models are proposed: a model that predicts the rack intake temperature (so that the temperature risk can be evaluated in support of energy-saving measures implemented in the server room) and a model that evaluates the energy-saving effect (in relation to a baseline). Specifically, the models were constructed by using machine learning. The first constructed model evaluates the temperature risk in a verification room in advance, and it was confirmed that the model can evaluate the risk beforehand with high accuracy. The second constructed model—“baseline model” hereafter—supports energy-saving measures, and it was confirmed that the model can calculate the baseline (energy consumption) with high accuracy as well. Moreover, the effect of proposal process of energy-saving measures in the verification room was verified by using the two proposed models. In particular, the effectiveness of the model for evaluating temperature risk in advance and that of a technology for visualizing the energy-saving effect were confirmed.
The Influence of Peptidases in Intestinal Brush Border Membranes on the Absorption of Oligopeptides from Whey Protein Hydrolysate: An Ex Vivo Study Using an Ussing Chamber
Authors: Ozorio Luísa , Mellinger-Silva Caroline , Cabral Lourdes M. C. , Jardin Julien , Boudry Gaelle , Dupont Didier
Published: October 2020

For many years, it was believed that only amino acids, dipeptides, and tripeptides could be absorbed and thus reach the bloodstream. Nowadays, the bioavailability of oligopeptides is also considered possible, leading to new research. This pilot study investigates the activity of brush border enzymes on undigested whey protein hydrolysate (WPH) and on simulated intestinal digested (ID) whey hydrolysate and the subsequent absorption of resultant peptides through the proximal jejunum of a 7-week old piglet setup in an Ussing chamber model. Amongst all samples taken, 884 oligopeptides were identified. The brush border peptidase activity was intense in the first 10 min of the experiment, producing several new peptides in the apical compartment. With respect to the ID substrate, 286 peptides were detected in the basolateral compartment after 120 min of enzyme activity, originating from β-lactoglobulin (60%) and β-casein (20%). Nevertheless, only 0.6 to 3.35% of any specific peptide could pass through the epithelial barrier and thus reach the basolateral compartment. This study demonstrates transepithelial jejunum absorption of whey oligopeptides in an ex vivo model. It also confirmed the proteolytic activity of brush border enzymes on these oligopeptides, giving birth to a myriad of new bioactive peptides available for absorption.
‘One Health’ Actors in Multifaceted Health Systems: An Operational Case for India
Authors: Yasobant Sandul , Bruchhausen Walter , Saxena Deepak , Falkenberg Timo
Published: October 2020

The surging trend of (re)emerging diseases urges for the early detection, prevention, and control of zoonotic infections through the One Health (OH) approach. The operationalization of the OH approach depends on the contextual setting, the presence of the actors across the domains of OH, and the extent of their involvement. In the absence of national operational guidelines for OH in India, this study aims to identify potential actors with an attempt to understand the current health system network strength (during an outbreak and non-outbreak situations) at the local health system of Ahmedabad, India. This case study adopted a sequential mixed methods design conducted in two phases. First, potential actors who have been involved directly or indirectly in zoonoses prevention and control were identified through in-depth interviews. A network study was conducted as part of the second phase through a structured network questionnaire. Interest and influence matrix, average degree, network density, and degree of centralization were calculated through Atlas.Ti (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany), UCINET (Analytic Technologies, Lexington, KY, USA) software. The identified actors were categorized based on power, administrative level (either at the city or district level), and their level of action: administrative (policy planners, managers), providers (physicians, veterinarians), and community (health workers, community leaders). The matrix indicated that administrative actors from the district level were ‘context setters’ and the actors from the city level were either ‘players’ or ‘subjects’. The network density showed a strength of 0.328 during the last outbreak of H5N1, which decreased to 0.163 during the non-outbreak situation. Overall, there was low collaboration observed in this study, which ranged from communication (during non-outbreaks) to coordination (during outbreaks). The private and non-governmental actors were not integrated into collaborative activities. This study concludes that not only collaboration is needed for OH among the sectors pertaining to the human and the animal health system but also better structured (‘inter-level’) collaboration across the governance levels for effective implementation.
In-Hospital Patient Safety Events, Healthcare Costs and Utilization: An Analysis from the Incident Reporting System in an Academic Medical Center
Authors: Kuo Yao-Wen , Jerng Jih-Shuin , Lin Chia-Kuei , Huang Hsiao-Fang , Chen Li-Chin , Li Yu-Tzu , Huang Szu-Fen , Hung Kuan-Yu
Published: October 2020

The possible association of patient safety events (PSEs) with the costs and utilization remains a concern. In this retrospective analysis, we investigated adult hospitalizations at a medical center between 2010 and 2015 with or without reported PSEs. Administrative and claims data were analyzed to compare the costs and length of stay (LOS) between cases with and without PSEs of the three most common categories during the first 14 days of hospitalization. Two models, including linear regression and propensity score-matched comparison, were performed for each reference day group of hospitalizations. Of 14,181 PSEs from 424,635 hospitalizations, 69.8% were near miss or no-harm events. Costs and LOS were similar between fall cases and controls in all of the 14 reference days. In contrast, for cases of tube and line events and controls, there were consistent differences in costs and LOS in the majority of the reference days (86% and 57%, respectively). Consistent differences were less frequently seen for medication events and control events (36% and 43%, respectively). Our study approach of comparing cases with PSEs and those without any PSE showed significant differences in costs and LOS for tube and line events, and medication events. No difference in cost or LOS was found regarding fall events. Further studies exploring adjustments for event risks and harm-oriented analysis are warranted.
Seed Geometry in the Arecaceae
Authors: Gutiérrez del Pozo Diego , Martín-Gómez José , Tocino Ángel , Cervantes Emilio
Published: October 2020

Fruit and seed shape are important characteristics in taxonomy providing information on ecological, nutritional, and developmental aspects, but their application requires quantification. We propose a method for seed shape quantification based on the comparison of the bi-dimensional images of the seeds with geometric figures. J index is the percent of similarity of a seed image with a figure taken as a model. Models in shape quantification include geometrical figures (circle, ellipse, oval…) and their derivatives, as well as other figures obtained as geometric representations of algebraic equations. The analysis is based on three sources: Published work, images available on the Internet, and seeds collected or stored in our collections. Some of the models here described are applied for the first time in seed morphology, like the superellipses, a group of bidimensional figures that represent well seed shape in species of the Calamoideae and Phoenix canariensis Hort. ex Chabaud. Oval models are proposed for Chamaedorea pauciflora Mart. and cardioid-based models for Trachycarpus fortunei (Hook.) H. Wendl. Diversity of seed shape in the Arecaceae makes this family a good model system to study the application of geometric models in morphology.
Encouraging Physical Activity during and after Pregnancy in the COVID-19 Era, and beyond
Authors: Atkinson Lou , De Vivo Marlize , Hayes Louise , Hesketh Kathryn R. , Mills Hayley , Newham James J. , Olander Ellinor K. , Smith Debbie M.
Published: October 2020

Physical activity is known to decline during pregnancy and the postnatal period, yet physical activity is recommended during this time due to the significant health benefits for mothers and their offspring. As a result of the COVID-19 pandemic and the restrictions imposed to reduce infection rates, pregnant and postnatal women have experienced disruption not just to their daily lives but also to their pregnancy healthcare experience and their motherhood journey with their new infant. This has included substantial changes in how, when and why they have engaged with physical activity. While some of these changes undoubtedly increased the challenge of being sufficiently active as a pregnant or postnatal woman, they have also revealed new opportunities to reach and support women and their families. This commentary details these challenges and opportunities, and highlights how researchers and practitioners can, and arguably must, harness these short-term changes for long-term benefit. This includes a call for a fresh focus on how we can engage and support those individuals and groups who are both hardest hit by COVID-19 and have previously been under-represented and under-served by antenatal and postnatal physical activity research and interventions.
How to Improve Patient Safety Literacy?
Authors: Kim Yoon-Sook , Kim Hyun Ah , Kim Moon-Sook , Kim Hyuo Sun , Kwak Mi Jeong , Chun Jahae , Hwang Jee-In , Kim Hyeran
Published: October 2020

The aim of this comparative study involving pre- and post-tests was to analyze the effectiveness of patient safety educational materials developed for the Comprehensive Plans for Patient Safety in Korea (2018–2022), and to suggest how to improve patient safety literacy. A face-to-face survey interview comprising items related to general information and patient safety literacy was completed by 217 patients and their families who visited three general hospitals in Seoul and one general hospital in Gyeonggi-do for treatment between 25 October and 15 November 2019. In the interview, the patients were asked questions about whether the patient safety educational materials were “easy to understand,” provided “help in safe hospitalization,” and enabled patients to practice patient safety independently (“do it yourself”). The literacy of the patient safety educational materials was analyzed using a paired t-test with a p value of 0.05. The comparison between patient safety literacy on pre- and post-tests revealed that among all participants, there were significant differences in “easy to understand,” “help in safe hospitalization,” and “do it yourself” scores. To improve patient safety literacy, patient education materials need to optimize communication by improving patients’ knowledge, skills, and attitudes for maintaining and promoting healthy living.
The Mortality Risk and Socioeconomic Vulnerability Associated with High and Low Temperature in Hong Kong
Authors: Liu Sida , Chan Emily Yang Ying , Goggins William Bernard , Huang Zhe
Published: October 2020

(1) Background: The adverse health effect associated with extreme temperature has been extensively reported in the current literature. Some also found that temperature effect may vary among the population with different socioeconomic status (SES), but found inconsistent results. Previous studies on the socioeconomic vulnerability of temperature effect were mainly achieved by multi-city or country analysis, but the large heterogeneity between cities may introduce additional bias to the estimation. The linkage between death registry and census in Hong Kong allows us to perform a city-wide analysis in which the study population shares virtually the same cultural, lifestyle and policy environment. This study aims to examine and compare the high and low temperature on morality in Hong Kong, a city with a subtropical climate and address a key research question of whether the extreme high and low temperature disproportionally affects population with lower SES. (2) Methods: Poisson-generalized additive models and distributed-lagged nonlinear models were used to examine the association between daily mortality and daily mean temperature between 2007–2015 with other meteorological and confounding factors controlled. Death registry was linked with small area census and area-level median household income was used as the proxy for socioeconomic status. (3) Results: 362,957 deaths during the study period were included in the analysis. The minimum mortality temperature was found to be 28.9 °C (82nd percentile). With a subtropical climate, the low temperature has a stronger effect than the high temperature on non-accidental, cardiovascular, respiratory and cancer deaths in Hong Kong. The hot effect was more pronounced in the first few days, while cold effect tended to last up to three weeks. Significant heat effect was only observed in the lower SES groups, whilst the extreme low temperature was associated with significantly higher mortality risk across all SES groups. The older population were susceptible to extreme temperature, especially for cold. (4) Conclusions: This study raised the concern of cold-related health impact in the subtropical region. Compared with high temperature, low temperature may be considered a universal hazard to the entire population in Hong Kong rather than only disproportionally affecting people with lower SES. Future public health policy should reconsider the strategy at both individual and community levels to reduce temperature-related mortality.
Identification of Entomopathogenic Fungi as Naturally Occurring Enemies of the Invasive Oak Lace Bug, Corythucha arcuata (Say) (Hemiptera: Tingidae)
Authors: Kovač Marta , Gorczak Michał , Wrzosek Marta , Tkaczuk Cezary , Pernek Milan
Published: October 2020

The oak lace bug (OLB), Corythucha arcuata (Hemiptera: Tingidae), was first identified as an invasive pest in Europe in northern Italy in 2000 and since then it has spread rapidly, attacking large forested areas in European countries. The OLB is a cell sap-sucking insect that is native to North America, with Quercus spp. as its main host. Its rapid expansion, successful establishment in invaded countries, and observations of more damage to hosts compared to native areas are most likely due to a lack of natural enemies, pathogens and competitors. In its native area, various natural enemies of OLBs have been identified; however, little is known about the occurrence and impact of OLB pathogens. None of the pathogenic fungi found on OLBs in natural conditions have been identified until now. In this study, we provide evidence of four entomopathogenic fungi that are naturally occurring on invasive OLBs found in infested pedunculate oak forests in eastern Croatia. On the basis of their morphology and multilocus molecular phylogeny, the fungi were identified as Beauveria pseudobassiana, Lecanicillium pissodis, Akanthomyces attenuatus and Samsoniella alboaurantium. The sequences generated for this study are available from GenBank under the accession numbers MT004817-MT004820, MT004833-MT004835, MT027501-MT27510, and MT001936-MT0011943. These pathogenic species could facilitate biological control strategies against OLBs.
CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma
Authors: Remer Eric , Badarni Mai , Hikri Elad , Dayan Avraham , Levi Lirit , Popovtzer Aron , Iraqi Muhammed , Porgador Angel , Joshua Ben-Zion , Bachar Gideon , Elkabets Moshe , Scaltriti Maurizio , Mizrachi Aviram
Published: October 2020

Activating alterations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in head and neck squamous cell carcinoma (HNSCC) and thought to be one of the main drivers of these tumors. However, early clinical trials on PI3K inhibitors (PI3Ki) have been disappointing due to the limited durability of the activity of these drugs. To investigate the resistance mechanisms to PI3Ki and attempt to overcome them, we conducted a molecular-based study using both HNSCC cell lines and patient-derived xenografts (PDXs). We sought to simulate and dissect the molecular pathways that come into play in PIK3CA-altered HNSCC treated with isoform-specific PI3Ki (BYL719, GDC0032). In vitro assays of cell viability and protein expression indicate that activation of the mTOR and cyclin D1 pathways is associated with resistance to PI3Ki. Specifically, in BYL719-resistant cells, BYL719 treatment did not induce pS6 and pRB inhibition as detected in BYL719-sensitive cells. By combining PI3Ki with either mammalian target of rapamycin complex 1 (mTORC1) or cyclin D1 kinase (CDK) 4/6 specific inhibitors (RAD001 and abemaciclib, respectively), we were able to overcome the acquired resistance. Furthermore, we found that PI3Ki and CDK 4/6 inhibitors have a synergistic anti-tumor effect when combined in human papillomavirus (HPV)-negative/PIK3CA-WT tumors. These findings provide a rationale for combining PI3Ki and CDK 4/6 inhibitors to enhance anti-tumor efficacy in HNSCC patients.
Predictors of Flares in Patients with Rheumatoid Arthritis Who Exhibit Low Disease Activity: A Nationwide Cohort Study
Authors: Oh Yoon-Jeong , Moon Ki Won
Published: October 2020

Using nationwide cohort data, this study evaluated predictors of flares in patients with rheumatoid arthritis (RA) who exhibit low disease activity (LDA) and the effects of flares on clinical outcomes. The Korean Observational Study Network for Arthritis (KORONA) registry is a nationwide Korean RA-specific cohort registry that collects data annually from 5.077 patients, with RA in 23 centers across South Korea. This study used data from 1.717 patients with RA who exhibited LDA [28–joint disease activity score (DAS28) < 3.2] at enrollment. Flares were defined as an increase in DAS28, compared with the previous value of > 1.2 or > 0.6, if the concurrent DAS28 was ≥ 3.2. Cox regression analysis was used to identify baseline predictors of flares. Of the 1.717 patients with RA, 566 (33.0%) experienced flares during the 2-year study period. An analysis of baseline characteristics of flare and non-flare groups revealed that more women and non-smokers were present in the flare group than in the non-flare group; the flare group also had higher scores on physician’s and patient’s pain and fatigue visual analogue scales (VAS) and the health assessment questionnaire (HAQ). In a multivariate analysis, physician’s VAS score, hemoglobin level, and HAQ score were significant predictors of flares. A high physician’s VAS score, low hemoglobin, and high HAQ score at baseline were significant predictors of flares in patients with RA who exhibited LDA.
Changing Trends in Hospital Admissions for Pulmonary Embolism in Spain from 2001 to 2018
Authors: de Miguel-Diez Javier , Albaladejo-Vicente Romana , Lopez-de-Andres Ana , Hernández-Barrera Valentín , Jiménez David , Monreal Manuel , Carabantes-Alarcon David , Zamorano-Leon José Javier , Jimenez-Garcia Rodrigo
Published: October 2020

(1) Background: The aims of this study were to examine trends in the incidence, clinical characteristics, and in-hospital outcomes of patients hospitalized with pulmonary embolism in Spain and to identify factors associated with in-hospital mortality (IHM). (2) Methods: We included all patients who were hospitalized for pulmonary embolism between 2001 and 2018. Data were collected from the Spanish National Hospital Discharge Database. (3) Results: We identified 241,821 hospitalizations for pulmonary embolism during the study period. The incidence of pulmonary embolism increased from 20.49 cases per 100,000 inhabitants in the period 2001–2002 to 35.9 cases in the period 2017–2018 (p < 0.001). After controlling for possible confounders, there was a significant increase in the incidence over the study period (adjusted incidence rate ratio 1.53, 95% Confidence Interval I 1.51–1.56). The median length of hospital stay was 11 days in the period 2001–2002, decreasing to seven days in the period 2017–2018 (p < 0.001). For the total time period, the crude IHM rate was 9.51%. After multivariable adjustment, IHM decreased significantly over time. The IHM was significantly higher in women, in patients suffering from more comorbidities, and in those with a massive pulmonary embolism. (4) Conclusions: Our results revealed an increase in the incidence of pulmonary embolism hospitalizations from 2001 to 2018 in Spain, with older patients being the most affected.
Isavuconazole—Animal Data and Clinical Data
Authors: Pagano Livio , Cattaneo Chiara , Quattrone Martina , Oberti Margherita , Mazzitelli Maria , Trecarichi Enrico Maria
Published: October 2020

The treatment of invasive fungal infections has deeply evolved in the last years with the inclusion of new antifungals, mainly new azoles (i.e., posaconazole, isavuconazole), to the therapeutic armamentarium. This review focuses on the role of isavuconazole for treating the most important invasive fungal infections both in animals and humans (hematological and non-hematological patients).
Build Size and Orientation Influence on Mechanical Properties of Powder Bed Fusion Deposited Titanium Parts
Authors: Mertová Kateřina , Džugan Ján , Roudnická Michaela , Daniel Matěj , Vojtěch Dalibor , Seifi Mohsen , Lewandowski John J.
Published: October 2020

This paper explores the influence of sample thickness and build orientation on the microstructure and mechanical properties of electron beam melting (EBM) additive manufactured Ti-6Al-4V titanium alloy and compared to previously published work on SLM-processed material. In particular, the various mechanical properties (tensile yield strength, ultimate tensile strength) were investigated with attempts to correlate with various microstructural features, including lamellae thickness, porosity and the size of prior-beta grains. However, it is shown that the surface exerts a dominant effect on mechanical properties with as-deposited surfaces. These observations provide the possibility for the further improvement of processing/property relations with as-deposited surfaces.
Hot Deformation and Dynamic Recrystallization Behavior of CoCrNi and (CoCrNi)94Ti3Al3 Medium Entropy Alloys
Authors: Yi Hai-long , Wei Daixiu , Wang Yingchen , Wang Liqiang , Fang Ming-yang , Yang Kang , Kato Hidemi
Published: October 2020

The CoCrNi and precipitate-hardened (CoCrNi)94Ti3Al3 medium entropy alloys (MEAs) have attracted much attention, due to their exceptional mechanical properties, whereas the hot deformation characteristics have not been revealed. In the present study, we investigated the dynamic recrystallization behavior and microstructure evolutions of the two MEAs hot-compressed at single-phase temperatures. The constitutive equation was obtained, and microstructures were observed. Discontinuous dynamic recrystallization acted as a key mechanism of grain refinement at a relatively higher temperature and lower strain rate, which leads to the formation of a homogeneous grain structure. The addition of Ti and Al promoted dynamic recrystallization due to the solid solution hardening effect. The results provide valuable guidelines for microstructure refinement via thermomechanical processing.
Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro)
Authors: Abu-Melha Sraa , Edrees Mastoura M. , Riyadh Sayed M. , Abdelaziz Mohamad R. , Elfiky Abdo A. , Gomha Sobhi M.
Published: October 2020

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.
Recent Techniques in Nutrient Analysis for Food Composition Database
Authors: Md Noh Mohd Fairulnizal , Gunasegavan Rathi Devi-Nair , Mustafa Khalid Norhayati , Balasubramaniam Vimala , Mustar Suraiami , Abd Rashed Aswir
Published: October 2020

Food composition database (FCD) provides the nutritional composition of foods. Reliable and up-to date FCD is important in many aspects of nutrition, dietetics, health, food science, biodiversity, plant breeding, food industry, trade and food regulation. FCD has been used extensively in nutrition labelling, nutritional analysis, research, regulation, national food and nutrition policy. The choice of method for the analysis of samples for FCD often depends on detection capability, along with ease of use, speed of analysis and low cost. Sample preparation is the most critical stage in analytical method development. Samples can be prepared using numerous techniques; however it should be applicable for a wide range of analytes and sample matrices. There are quite a number of significant improvements on sample preparation techniques in various food matrices for specific analytes highlighted in the literatures. Improvements on the technology used for the analysis of samples by specific instrumentation could provide an alternative to the analyst to choose for their laboratory requirement. This review provides the reader with an overview of recent techniques that can be used for sample preparation and instrumentation for food analysis which can provide wide options to the analysts in providing data to their FCD.
Photoluminescence as a Valuable Tool in the Optical Characterization of Acetaminophen and the Monitoring of Its Photodegradation Reactions
Authors: Daescu Monica , Matea Adelina , Negrila Catalin , Serbschi Constantin , Ion Alina C. , Baibarac Mihaela
Published: October 2020

In this work, new evidence for the photodegradation reactions of acetaminophen (AC) is reported by photoluminescence (PL), Raman scattering and FTIR spectroscopy. Under excitation wavelength of 320 nm, AC shows a PL band in the spectral range of 340–550 nm, whose intensity decreases by exposure to UV light. The chemical interaction of AC with the NaOH solutions, having the concentration ranging between 0.001 and 0.3 M, induces a gradual enhancement of the photoluminescence excitation (PLE) and PL spectra, when the exposure time of samples at the UV light increases until 140 min, as a result of the formation of p-aminophenol and sodium acetate. This behavior is not influenced by the excipients or other active compounds in pharmaceutical products as demonstrated by PLE and PL studies. Experimental arguments for the obtaining of p-aminophenol and sodium acetate, when AC has interacted with NaOH, are shown by Raman scattering and FTIR spectroscopy.
A Bibenzyl Component Moscatilin Mitigates Glycation-Mediated Damages in an SH-SY5Y Cell Model of Neurodegenerative Diseases through AMPK Activation and RAGE/NF-κB Pathway Suppression
Authors: Lai Mei Chou , Liu Wayne Young , Liou Shorong-Shii , Liu I-Min
Published: October 2020

Moscatilin can protect rat pheochromocytoma cells against methylglyoxal-induced damage. Elimination of the effect of advanced glycation end-products (AGEs) but activation of AMP-activated protein kinase (AMPK) are the potential therapeutic targets for the neurodegenerative diseases. Our study aimed to clarify AMPK signaling’s role in the beneficial effects of moscatilin on the diabetic/hyperglycemia-associated neurodegenerative disorders. AGEs-induced injury in SH-SY5Y cells was used as an in vitro neurodegenerative model. AGEs stimulation resulted in cellular viability loss and reactive oxygen species production, and mitochondrial membrane potential collapse. It was observed that the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase increased in SH-SY5Y cells following AGEs exposure. AGEs decreased Bcl-2 but increased Bax and p53 expression and nuclear factor kappa-B activation in SH-SY5Y cells. AGEs also attenuated the phosphorylation level of AMPK. These AGEs-induced detrimental effects were ameliorated by moscatilin, which was similar to the actions of metformin. Compound C, an inhibitor of AMPK, abolished the beneficial effects of moscatilin on the regulation of SH-SY5Y cells’ function, indicating the involvement of AMPK. In conclusion, moscatilin offers a promising therapeutic strategy to reduce the neurotoxicity or AMPK dysfunction of AGEs. It provides a potential beneficial effect with AGEs-related neurodegenerative diseases.
Topical Application of Aronia melanocarpa Extract Rich in Chlorogenic Acid and Rutin Reduces UVB-Induced Skin Damage via Attenuating Collagen Disruption in Mice
Authors: Her Young , Lee Tae-Kyeong , Kim Jong Dai , Kim Bora , Sim Hyejin , Lee Jae-Chul , Ahn Ji Hyeon , Park Joon Ha , Lee Ji-Won , Hong Junkee , Kim Sung-Su , Won Moo-Ho
Published: October 2020

Aronia melanocarpa, a black chokeberry, contains high levels of phenolic acids and polyphenolic flavonoids and displays antioxidative and anti-inflammatory effects. Through high-performance liquid chromatography for extracts from Aronia melanocarpa, we discovered that the extract contained chlorogenic acid and rutin as major ingredients. In this study, we examined the protective effects of the extract against ultraviolet B- (UVB)-induced photodamage in the dorsal skin of institute of cancer research (ICR) mice. Their dorsal skin was exposed to UVB, thereafter; the extract was topically applied once a day for seven days. Photoprotective properties of the extract in the dorsal skin were investigated by clinical skin severity score for skin injury, hematoxylin and eosin staining for histopathology, Masson’s trichrome staining for collagens. In addition, we examined change in collagen type I and III, and matrix metalloproteinase (MMP)-1 and MMP-3 by immunohistochemistry. In the UVB-exposed mice treated with the extract, UVB-induced epidermal damage was significantly ameliorated, showing that epidermal thickness was moderated. In these mice, immunoreactivities of collagen type I and III were significantly increased, whereas immunoreactivities of MMP-1 and 3 were significantly decreased compared with those in the UVB-exposed mice. These results indicate that treatment with Aronia melanocarpa extract attenuates UV-induced photodamage by attenuating UVB-induced collagen disruption: these findings might be a result of the chlorogenic acid and rutin contained in the extract. Based on the current results, we suggest that Aronia melanocarpa can be a useful material for developing photoprotective adjuvant.