bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting potential druggable targets against SARS‐CoV‐2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review
Authors: Sohag Abdullah Al Mamun , Hannan Md Abdul , Rahman Sadaqur , Hossain Motaher , Hasan Mahmudul , Khan Md Kawsar , Khatun Amena , Dash Raju , Uddin Md Jamal 
Published: July 2020

AbstractCoronavirus disease‐19 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID‐19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS‐CoV‐2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target‐based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti‐SARS‐CoV‐2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS‐CoV‐2 infection.
Increasing engagement in pharmacology and pharmacogenetics education using games and online resources: The PharmacoloGenius mobile app
Authors: Zammarchi Gianpaolo , Del Zompo Maria , Squassina Alessio , Pisanu Claudia 
Published: July 2020

AbstractMobile applications represent useful instruments to convey information and engage the users even during traveling, thanks to the wide diffusion of smartphones, tablets, smartwatches, and similar devices. As such, they have high potential as learning tools that can act complementary to traditional teaching approaches. In the field of pharmacology, mobile applications are increasingly being used to improve adherence of patients or to help them report suspect adverse drug reactions. However, they have been scarcely applied to pharmacology education. In this article, we present PharmacoloGenius, a free Android mobile application integrating resources useful for students as well as healthcare professionals or researchers to expand knowledge on pharmacological topics. We gave particular emphasis to pharmacogenetics, as it is a fundamental tool to achieve personalized treatment. The application offers original games such as pharmacological trivia based on textbooks or special “journal club” trivia based on research articles conveying the state of the art on specific topics. Additionally, the app offers a curated list of online resources to study pharmacology and pharmacogenetics (e.g., free online courses, videos, and databases) as well as updated news on conferences, grants, and opportunities for pharmacologists. In conclusion, PharmacoloGenius aims to be a useful instrument for people interested in expanding their knowledge on pharmacology in an engaging way.
Multiple epiphyseal dysplasia and related disorders: Molecular genetics, disease mechanisms, and therapeutic avenues
Authors: Dennis Ella P. , Greenhalgh‐Maychell Phillippa L. , Briggs Michael D. 
Published: July 2020

AbstractFor the vast majority of the 6000 known rare disease the pathogenic mechanisms are poorly defined and there is little treatment, leading to poor quality of life and high healthcare costs. Genetic skeletal diseases (skeletal dysplasias) are archetypal examples of rare diseases that are chronically debilitating, often life‐threatening and for which no treatments are currently available. There are more than 450 unique phenotypes that, although individually rare, have an overall prevalence of at least 1 per 4000 children. Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous disorder characterized by disproportionate short stature, joint pain, and early‐onset osteoarthritis. MED is caused by mutations in the genes encoding important cartilage extracellular matrix proteins, enzymes, and transporter proteins. Recently, through the use of various cell and mouse models, disease mechanisms underlying this diverse phenotypic spectrum are starting to be elucidated. For example, ER stress induced as a consequence of retained misfolded mutant proteins has emerged as a unifying disease mechanisms for several forms of MED in particular and skeletal dysplasia in general. Moreover, targeting ER stress through drug repurposing has become an attractive therapeutic avenue.
A small‐tiled geographic mosaic of coevolution between Eurosta solidaginis and its natural enemies and host plant
Authors: Craig Timothy P. , Livingston‐Anderson Annelie , Itami Joanne K. 
Published: July 2020

AbstractWe identified a geographic mosaic of Eurosta solidaginis fly traits produced by coevolution of the stem gall‐forming fly with both its natural enemies and its host plants at small geographic scales in the presence of gene flow. These tritrophic interactions between the fly with its natural enemies and with its host‐plant Solidago altissima produced what has been termed a small‐tiled geographic mosaic of coevolution. Selection on gall diameter and length varies between prairie and forest habitats due to differences in host plants and natural‐enemy communities. At the prairie–forest ecotone where prairie and forest habitats are intermixed, we found that geographic selection mosaics on gall diameter and length varied on a scale of a few kilometers. Gall diameter variation among sites correlated with selection on gall diameters, indicating local adaptation. In contrast, gall lengths did not correlate with selection, indicating that gene flow may have prevented local adaptation of this trait. Eastern (forest) and western (prairie) subspecies of E. solidaginis have been proposed based on fly wing patterns, and these had intermediate forms in the ecotone indicating gene flow between these subspecies. Variation in wing patterns correlated with gall diameter, indicating that gene flow between prairie and forest fly populations may influence the distribution of gall traits. The ratio of forest to prairie vegetation increases with latitude, but there was no indication of latitudinal clines in gall or wing traits. Our results indicate that selection for differentiation in coevolved traits is strong enough to overcome gene flow in small tiles of habitat. The result is that ecological forces produce a dynamic mosaic of genetically differentiated locally adapted populations. It also indicates that prairie and forest host races of E. solidaginis form a mosaic hybrid zone in this region.
Three‐dimensional Modeling and Performance Optimization of Proton Conducting Solid Oxide Electrolysis Cell▴
Authors: Wang Y. , Zu B. , Zhan R. , Du Q. , Ni M. , Jiao K. 
Published: July 2020

AbstractIn this study, a three‐dimensional model is developed to study a novel proton conducting solid oxide electrolysis cell (H‐SOEC) with porous current collector to alleviate the H2O‐starvation problem in oxygen electrode. The comparison between conventional straight‐channel structure and the new porous structure is conducted in detail. It is found that the porous current collector can increase the flow uniformity and facilitate the diffusion of H2O, which in turn improves the average performance of the H‐SOEC. The electrolysis efficiency can be increased by 6.4% compared to straight‐channel structure. It is also found that the thermal neutral voltage is decreased when the porous current collector is adopted. Besides, the evaluation of syngas production for CO2‐supplied H‐SOEC is performed. Compared to H2 production, the efficiency of syngas production can be increased by up to 13.5%.
Framing and signalling effects of taxes on sugary drinks: A discrete choice experiment among households in Great Britain
Authors: Cornelsen Laura , Quaife Matthew , Lagarde Mylene , Smith Richard D. 
Published: July 2020

AbstractTaxes on sugar‐sweetened beverages (SSBs) are in place in many countries to combat obesity with emerging evidence that these are effective in reducing purchases of SSBs. In this study, we tested whether signalling and framing the price increase from an SSB tax explicitly as a health‐related, earmarked measure reduces the demand for SSBs more than an equivalent price increase. We measured the demand for non‐alcoholic beverages with a discrete choice experiment (DCE) administered online to a randomly selected group of n = 603 households with children in Great Britain (GB) who regularly purchase SSBs. We find a suggestive evidence that a price increase leads to a larger reduction in the probability of choosing SSBs when it is signalled as a tax and framed as a health‐related and earmarked policy. Respondents who did not support a tax on SSBs, who were also more likely to choose SSBs in the first place, were on average more responsive to a price increase framed as an earmarked tax than those who supported the tax. The predictive validity of the DCE, to capture preferences for beverages, was confirmed using actual purchase data. The findings imply that a well‐signalled and earmarked tax on SSBs could improve its effectiveness at reducing the demand.
Cash‐based maternal health interventions can improve childhood vaccination—Evidence from India
Authors: De Prabal K. , Timilsina Laxman 
Published: July 2020

AbstractChildhood vaccination has lagged in countries like India, despite its demonstrated positive effects on health outcomes like infant mortality. At the same time, many conditional cash transfer programs have been effective in improving health outcomes. We estimate the effect of the world's largest maternal health program, Janani Suraksha Yojana (JSY, maternal protection scheme), on childhood vaccination in India. We exploit exogenous variations in the expansion of the policy around the country and the fact that some key vaccines are given at or near birth to identify the effects of cash‐based maternal health policy on infant immunization. We find that JSY increased the probability of Bacillus Calmette–Guérin (BCG) and diphtheria, pertussis, and tetanus toxoid (DPT) vaccination among newborns and infants. However, we find almost no significant effects on the measles vaccine, which is administered several months after birth.
Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma
Authors: Holmes Brittany J. , von Eyben Rie , Attardi Laura D. , Kong Christina S. , Le Quynh‐Thu , Nathan Cherie‐Ann O. 
Published: July 2020

AbstractBackgroundPERP (p53 apoptosis effector related to PMP22) localizes to desmosomes and suppresses squamous cell carcinoma development. Loss of PERP leads to worse local control in head and neck squamous cell carcinoma (HNSCC), likely by destabilizing desmosomes. We evaluated PERP loss at HNSCC surgical margins as a predictor of local relapse.MethodsCombining discovery (n = 17) and validation (n = 31) cohorts, we examined membranous PERP protein expression by immunohistochemistry in surgical mucosal margins with competing risk analysis of the relationship between local relapse and PERP expression.ResultsOf the 44 analyzable patients, the 2‐year cumulative incidence of local relapse was 44.4% for the PERP‐negative group and 16.4% for the PERP‐positive group (P = .01). A trend toward worse progression‐free survival (P = .09) and overall survival (P = .06) was observed with loss of PERP.ConclusionsPERP loss at surgical margins is associated with higher risk of local recurrence in HNSCC, warranting further evaluation in a larger prospective study.
Water and Sediment Quality in the Coastal Zone Around the Mouth of Doce River After the Fundão Tailings Dam Failure
Authors: Richard Eduardo da Cunha , Estrada Gustavo Calderucio Duque , Bechtold Jean-Philippe , de Aguiar Duarte Helvecio , Maioli Brigida Gusso , de Freitas Antonio Henrique Araujo , Warner Kara Elizabeth , Figueiredo Luis Henrique Melges 
Published: July 2020

Abstract
Fundão dam (Minas Gerais, Brazil) breached on 5 November 2015, releasing 50 million m³ of Fe ore tailings and dam materials into the upper Doce River system. The tailings travelled 670 km along the river system to the ocean. Starting on 17 November 2015, 6 days before the tailings reached the Doce River mouth, a water quality monitoring program with a daily sampling schedule was implemented by Samarco Mineração S.A. (Samarco) to assess the impacts on marine water and sediment quality. Between November 2015 and August 2017 water and sediment quality were monitored at 28 locations offshore from the Doce River mouth. The sampling areas were grouped by hydrological and metocean season (i.e., rainy and dry seasons and wave and wind climates), distance from the river mouth (&lt;5 km, &gt;5 km and within a Marine Protected Area), and water depth. The data were compared to the Brazilian water quality standards and prebreach conditions. Statistical tests were conducted to evaluate temporal and spatial trends and patterns. For the water quality parameters of relevance (total suspended solids, turbidity, total and dissolved Fe, Al, and Mn), pulses of concentration increases were observed right after the arrival of the plume in the coastal zone and during the subsequent rainy seasons. Exceedances of prebreach conditions were more frequent closer to the Doce River mouth. During the dry season, concentrations tended to decrease, reaching prebreach levels for a number of parameters, with small short-term pulses associated with metocean factors. For sediment quality parameters of relevance (particle size, Fe, Al, and Mn), Fe was the only one that clearly resulted from the dam breach, which was mediated by river influence and oceanographic factors affecting particle size distribution. Results indicated that the Fundão dam failure did affect water and sediment quality in the Atlantic Ocean, with greater impacts closer to the river mouth and immediately after the arrival of the tailings plume, with concentrations gradually returning to preevent levels over time. Integr Environ Assess Manag 2020;16:643–654. © 2020 SETAC
Earnings informativeness and trading frequency: Evidence from African markets
Authors: Jones Edward A. E. , Kyiu Anthony K. , Li Hao 
Published: July 2020

AbstractWe investigate the informativeness of earnings announcements in African stock markets and examine whether, conditional on the level of synchronicity and liquidity of stocks, market reactions are influenced by earnings characteristics. Normalized volatility indicates that earnings announcements are informative across the sample. The results are driven by less frequently traded stocks and informativeness manifests more clearly at announcement and in the post‐announcement window. There is little evidence of leakage. Informativeness is also present for highly traded stocks, notably after announcement. Cross‐sectional tests provide evidence of an effect of both earnings fundamentals and investor behaviour on stock returns around earnings announcements.
Cantharidin‐induced LO2 cell autophagy and apoptosis via endoplasmic reticulum stress pathway in vitro
Authors: Liu Fang , Duan Cancan , Zhang Jianyong , Li Xiaofei 
Published: July 2020

AbstractCantharidin (CTD), an important active compound derived from the traditional Chinese medicine Mylabris (also called Banmao), has been used in the treatment of diseases such as tumors and dermatosis. However, Mylabris has been shown to induce hepatotoxicity in clinical practice and animal experiments, limiting its use. Further, a detailed mechanism underlying CTD‐induced hepatotoxicity has not been determined. In the present study, we aimed to explore the effect of endoplasmic reticulum stress (ERS), autophagy, and apoptosis on CTD‐induced hepatotoxicity. We found that CTD could inhibit the proliferation of LO2 cells; increase alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and malondialdehyde levels; and reduce glutathione peroxidase and superoxide dismutase activities. Western blotting showed that low concentrations of CTD induced the expressions of ERS‐related proteins [GRP78, ATF4, PERK, p‐PERK, XBP1–1 s, and CHOP], but high concentrations of CTD inhibited their expressions. Furthermore, high concentrations of CTD activated autophagy (LC3, Beclin‐1, Atg3, Atg4A, Atg4B, and Atg7), induced the expressions of apoptotic proteins (Bax/Bcl‐2 and caspase‐3), and increased LO2 toxicity. Taken together, these results indicated that CTD can induce LO2 cytotoxicity by inhibiting ERS and inducing autophagy and apoptosis, which provides a scientific basis for CTD‐induced hepatotoxicity.
Micromorphological and cytological comparisons between Youngia japonica and Youngia longiflora using light and scanning electron microscopy
Authors: Choi Bokyung , Kim Sun‐Yu , Jang Tae‐Soo 
Published: July 2020

AbstractThe genus Youngia Cass. is taxonomically complex and widely distributed in East Asia. Despite the high diversity of species, only two species, Youngia japonica (L.) DC. and Youngia longiflora (Babc. & Stebbins) C.Shih, are currently found in Korea. Among them, Y. longiflora was once recognized as a subspecies of Y. japonica. However, based on chloroplast and nuclear DNA sequences, as well as morphology, Y. longiflora was found to be a distinct species. Here, the two Korean Youngia species were analyzed using scanning electron microscope and light microscope for chromosome number, pollen, cypselae, and leaf micromorphological characters to evaluate if the examined characters are informative for taxonomy. Pollen morphology is described, and the micromorphological characters of Y. longiflora are described for the first time. Cypselae and pollen surface ornamentation, as well as trichome morphology and stomatal size varied between the two species. Y. japonica had longer chromosomes than Y. longiflora, while other chromosomal characters including the localization of the NOR (nucleolar organizer region) were similar. The present micromorphological and cytological results are of great taxonomic value for Youngia species identification in Korea.
Aneurysms of pancreaticoduodenal arcade: Clinical profile and endovascular strategies
Authors: Sharma Supriya , Prasad Raghunanadan , Gupta Archna , Dwivedi Pranav , Mohindra Samir , Yadav Rajanikant R 
Published: July 2020

AbstractBackground and AimPancreaticoduodenal arcade aneurysms (PDAAs) are uncommon lesions associated with a significant risk of rupture and mortality. This study describes the etiology, clinical presentation, and endovascular management strategies of PDAAs across a spectrum of indications.MethodsThe clinical records of patients with PDAAs referred for endovascular management from January 2018 till November 2019 were retrospectively reviewed. Data on presenting symptoms, associated etiologies, and outcomes after endovascular treatment were collected and studied.ResultsWe found 15 patients with false and 1 patient with true aneurysm of pancreatoduodenal arcade (PDA). The associated conditions were coeliac artery stenosis, severe necrotizing pancreatitis, and chronic pancreatitis or iatrogenic (postendoscopic papillotomy and percutaneous metallic biliary stenting). The main presenting feature was gastrointestinal bleed, while 2 patients had abdominal pain and 1 had gastric outlet obstruction. A multiphase computed tomography scan demonstrated the ruptured aneurysm in all patients. Site of origin of PDAA influenced the choice of transarterial endovascular strategy (coiling for aneurysms of main trunk of arteries and glue injection for those arising from small arterial branches). This was carried out in an emergency setting for 12 patients and as an elective procedure in 4 patients. Technical success was demonstrated in all patients and clinical success in 14. The two patients who had rebleed were salvaged by repeat endovascular procedure. Postembolization syndrome was seen in three patients.ConclusionsWith advancing technology, endovascular strategies continue to evolve. Careful attention to ensure hemodynamic resuscitation and stability, correction of pre‐existing coagulopathy and attention to technique can lead to the possibility of endovascular approaches as a dependable option in the management of ruptured PDAAs.
BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy
Authors: McGee Michael C , August Avery , Huang Weishan 
Published: July 2020

Abstract
Bruton’s tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID-19 immunopathology. Clinical trials with BTK inhibitors in COVID-19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID-19. Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.
Genetic characterization of dengue virus serotype 2 isolated from dengue fever outbreaks in eastern Uttar Pradesh and western Bihar, India
Authors: Deval Hirawati , Behera Sthita P. , Agrawal Awdhesh , Singh Rajeev , Misra Brijranjan , Janardhan Vanka , Patil Gajanan , Sah Kamlesh , Kumar Niraj , Singh Ravishankar , Bondre Vijay P. 
Published: July 2020

AbstractDengue (DEN) is the most common cause of mosquito‐borne endemic viral diseases in the tropical and subtropical countries. DEN outbreaks associated with multiple dengue virus (DV) serotypes have been regularly reported in different parts of India. This study was done during DEN outbreaks in 2015 to 2016 in UP and Bihar where DEN‐2 was found as the only prevalent serotype. DV‐2 was the only serotype amplified in serotype‐specific reverse‐transcription polymerase chain reaction from sera of 210 (65.21%) out of 322 DV NS1 antigen‐positive patients. Further genetic analysis based on full‐length envelope (E) protein sequence derived from patient's sera as well as DV isolate showed the circulation of lineages I and III of DV‐2 cosmopolitan genotype during 2015 and lineage II during 2016. Finally, the phylogenetic analysis using the E gene sequence revealed that these DV‐2 strains have a close genetic relationship with the recently reported DV‐2 genotypes from DEN outbreaks reported from different parts of north India. These results showed the circulation of cosmopolitan genotype of DV‐2 in eastern Uttar Pradesh and western Bihar, India. The genetic database generated on circulating DV strains in this study will be useful as reference for disease surveillance and strengthening laboratory diagnosis protocols.