bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the pharmacokinetic‐pharmacodynamic cut‐off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing
Authors: Bousquet‐Mélou Alain , Schneider Marc , El Garch Farid , Broussou Diane C. , Ferran Aude A. , Lallemand Elodie A. , Triboulloy Cyrielle , Damborg Peter , Toutain Pierre‐Louis 
Published: November 2020

AbstractBackgroundMarbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses.ObjectivesTo compute PK/PD cut‐offs (PK/PDCO) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation.Study designA meta‐analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings.MethodsHorses (n = 131) received MBX intravenously at doses of either 2 or 10 mg/kg BW. They were richly sampled (five or six samples per horse). A population model was built to generate a virtual population of 5000 MBX disposition curves by Monte Carlo simulations (MCS) over 24 hours. The selected PK/PD index was the ratio of Area Under the free plasma concentration‐time Curve divided by the MIC (fAUC/MIC). The PK/PDCO, which is the highest MIC for which 90% of horses can achieve an a priori selected critical value for the numerical value of the PK/PD index, was established for Gram‐positive and Gram‐negative bacteria for a dose of 2 mg/kg.ResultsThe PK/PDCO of MBX in horses was 0.125 mg/L for Gram‐positive pathogens and 0.0625 mg/L for Gram‐negative pathogens. MBX MICs determined by broth microdilution for 54 Escherichia coli and 189 Streptococcus equi isolates are reported.Main limitationNo clinical data are taken into account in the determination of a PK/PDco.ConclusionThe computed PK/PDco predicts that MBX may be efficacious in horses to treat infections associated with Enterobacteriaceae but unlikely to those involving Staphylococcus aureus or Streptococcus equi.
Prediction of COVID‐19 active cases using exponential and non‐linear growth models
Authors: Mahanty Chandrakanta , Kumar Raghvendra , Mishra Brojo Kishore , Hemanth D. Jude , Gupta Deepak , Khanna Ashish 
Published: November 2020

AbstractWorld Health Organization recognized COVID‐19 as a pandemic on March 11, 2020. A total of 213 countries and territories around the world have reported a total of 27,948,441 confirmed cases as on September 9, 2020. This article adopted two non‐linear growth models (Gompertz, Verhulst) and exponential model (SIR) to analyse the coronavirus pandemic across the world. All the models have been used for active COVID‐19 patients predictions based on the data collected from John Hopkins University repository in the time period of January 30, 2020 to June 4, 2020. Outbreak of COVID‐19 disease has been analysed for India, Pakistan, Myanmar (Burma), Brazil, Italy and Germany till June 4, 2020 and predictions have been made for the number of positive cases for the next 28 days. Verhulst model fitting effect is better than Gompertz and SIR model with R‐score 0.9973. The proposed model perform better as compare to other three existing models with R‐score 0.9981.These above models can be adapted to forecast in long term intervals, based on the predictions for a short interval as of June 5, 2020 and June 30, 2020, active COVID‐19 patients for India, Pakistan, Italy, Germany, Brazil and Myanmar predicted as (236,170, 88,998, 234,066, 184,922, 645,057 and 235) and (486,357, 218,864, 240,545, 193,727, 1,211,567 and 309).
Development of pyrazole derivatives in the management of inflammation
Authors: Turones Larissa Córdova , Martins Aline Nazareth , Moreira Lorrane Kelle da Silva , Fajemiroye James Oluwagbamigbe , Costa Elson Alves 
Published: November 2020

AbstractThe therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis of the first pyrazole—antipyrine in 1887, several other derivatives have been screened for anti‐inflammatory, analgesic, and antipyretic activities. Arguably, the pyrazole ring, as a major pharmacophore and central scaffold partly, defines the pharmacological profile of several derivatives. In this review, we explore the structural–activity relationship that accounts for the pharmacological profile of pyrazole derivatives and highlights future research perspectives capable of optimizing current advancement in the search for safe and efficacy anti‐inflammatory drugs. The flourishing research into the pyrazole derivatives as drug candidates has advanced our understanding of inflammation‐related diseases and treatment.
Time will tell: Revisiting the impact of college expansion on income and occupational prestige mobility of young adults in Taiwan
Authors: Kuan Ping‐Yin , Peng Ssu‐Chin 
Published: November 2020

AbstractThe paper proposes a counterfactual analysis to estimate the causal effects of college expansion on the changes in income and occupational prestige of young people in Taiwan. The public attributes the rapid expansion of higher education in Taiwan in the mid 1990s as a significant cause of stagnant wage growth and high unemployment rates of college graduates in recent years. The primary concern in evaluating the policy consequences of educational expansion should be on those who would respond to expanded opportunities for education. In this paper, we use the data collected by the Panel Study of Family Dynamics in Taiwan to identify a pre‐expansion cohort and a post‐expansion cohort. We then use the matching method and the difference‐in‐difference (DID) model to estimate the impact of expansion on the changes in income and occupational prestige of three counterfactual groups: ‘always‐takers’, ‘compliers’, and ‘never‐takers’. The results show that the impact of college expansion decreased the advantage of always‐takers and benefited compliers in both income and occupational attainment of their first job. The adverse effects of college expansion suffered by always‐takers disappeared after working for either 10 or 15 years, which fits the prediction of the signalling theory.摘要本研究以反事實分析架構之角度，探討台灣高教擴張對年輕世代之薪資與職業流動的影響。本研究使用臺灣「華人家庭動態資料庫」於2003年及2009年的新增樣本及其後續追蹤調查，先配對並建構出無論高教擴張是否一定會上大學之「必為者」、順應高教擴張而有機會上大學之「順勢而為者」，以及無論高教擴張與否都不會上大學之「必不為者」等三類群體，藉此避免因擴張前後高教人口組成結構不同而無法直接比較的問題。研究結果發現，就順勢而為者言，高教擴張對其初職薪資和職業聲望有著正面影響，且持續到就業十年和十五年後；對必為者而言，高教擴張對其初職薪資和職業聲望有著負面影響，但雖著工作經驗的累積，該負面影響消失。整體而言，本文的研究成果支持訊號論的主張。
Changes in nutritional composition, enzyme activities and bioactive compounds of germinated buckwheat (Fagopyrum esculantum M.) under unchanged air and humidity conditions
Authors: Hung Pham Van , Trinh Le Ngoc Dang , Thuy Nguyen Thi Xuan , Morita Naofumi 
Published: November 2020

SummaryThe objective of this study was to investigate changes in nutritional and bioactive compounds in buckwheat seeds during germination under unchanged air and humidity conditions. The germination increased the crude protein, total lipid, reducing sugars, essential amino acids (EAA) and polyunsaturated fatty acids, but decreased the total ash, total carbohydrate and saturated fatty acids. After germinating for 48 h, the total EAA and polyunsaturated fatty acids significantly increased by 5.22% and 3.66%, respectively, as compared to those of ungerminated buckwheat. The total phenolics and flavonoids contents of both free and bound phenolic extracts of germinated buckwheat were also significantly higher than those of ungerminated buckwheat. The rutin content was found to gradually increase during germination, whereas the quercetin content was the highest in the 36 h‐germinated buckwheat (0.26 mg g−1 flour). Therefore, germinated buckwheat is considered as a potential material for producing healthy functional foods.
Adult genitourinary sarcoma: The era of optional chemotherapeutic agents for soft tissue sarcoma
Authors: Urasaki Tetsuya , Nakano Kenji , Tomomatsu Junichi , Komai Yoshinobu , Yuasa Takeshi , Yamashita Kyoko , Takazawa Yutaka , Yamamoto Shinya , Yonese Junji , Takahashi Shunji 
Published: November 2020

ObjectiveTo report our institutional experience with treatment of primary genitourinary soft tissue sarcoma.MethodsWe retrospectively reviewed the medical records of adult soft tissue sarcoma patients treated between March 2005 and May 2019. The primary tumor sites included the prostate, kidney, urinary bladder and the paratesticular structures.ResultsA total of 19 patients – 16 men (84%) and three women (16%) – were enrolled in the study. The median age was 41 years (range 20–79 years). The most common primary site was the prostate (in eight patients; 42%), and prostatic sarcoma patients were younger than patients with sarcomas of other origins. The most common histological subtype was leiomyosarcoma (in five patients; 26%). The overall survival rates after 1, 3 and 5 years were 61.5%, 34.4% and 25.8%, respectively. The median survival time was 20.7 months (95% confidence interval 5.9–35.5 months). Univariate analysis showed that an absence of metastasis at diagnosis and complete surgical resection were predictive of favorable survival. In the chemotherapy group, the objective response rate was 20.5%. Pazopanib was administered to nine patients in the late‐line setting, and the objective response rate was 11.1%; six grade ≥3 adverse events were observed in three patients.ConclusionsInoperable metastatic genitourinary soft tissue sarcoma remains difficult to treat, as previously reported. Further investigation on this malignancy, including optimization of currently available antitumor drugs and the development of novel therapeutic agents, is required.
Formation and stability of gismondine‐type zeolite in cementitious systems
Authors: Okoronkwo Monday U. , Mondal Sukanta K. , Wang Bu , Ma Hongyan , Kumar Aditya 
Published: November 2020

AbstractMicrocrystalline zeolites of the gismondine family are often reported in alkali‐activated and blended cement systems. However, little is known about gismondine's compatibility with other cementitious phases to determine stability in long‐term phase assemblage. Experimental studies were conducted to investigate the compositional field of gismondine stability in the lime‐alumina‐silica‐hydrate systems, with a particular focus on understanding the compatibility of gismondine with other cement phases such as C‐S‐H, ettringite, monosulfate, strätlingite, katoite, gypsum, calcite, portlandite, alkali, silica, and aluminosilicate phases. Results show that gismondine‐Ca forms readily at ~85°C in high aluminosilicate compositions; and persists in the presence of calcite, gypsum, ettringite, katoite solid solution, low Ca tobermorite‐like C‐S‐H, silica and aluminosilicate phases, at 20‐85°C. However, gismondine‐Ca reacts with: (a) monosulfate, producing ettringite‐thaumasite solid solution; (b) portlandite, forming tobermorite‐like C‐A‐S‐H gel and siliceous katoite at >55°C; (c) aqueous NaOH, generating gismondine‐(Na,Ca), a garronite‐like zeolite P solid solution; and (d) strätlingite leading to the conversion of strätlingite to gismondine indicating the metastability of strätlingite with respect to gismondine at 55°C. The outcomes are discussed to provide insights into the long‐term phase assemblage of relevant cement systems such as lime‐calcined clay, alkali‐activated materials, and potentially ancient Roman concrete.
Seeking consent for organ donation: Process evaluation of implementing a new Specialist Requester nursing role
Authors: Mc Laughlin Leah , Neukirchinger Barbara , Monks Jane , Duncalf Sue , Noyes Jane 
Published: November 2020

AbstractAimTo explain the differences in organ donation consent outcomes of a new nursing role (Specialist Requesters) derived from the United States (US) compared with the existing nursing role (Specialist Nurses in Organ Donation).DesignThirty‐month observational qualitative process evaluation: Implementation theory‐informed analysis.MethodsQualitative content analysis of free text describing challenges, processes and practice from 996 bespoke routinely collected potential organ donor ‘approach forms’ from two regions: one where there was no difference, and one with an observed difference in consent outcomes.ResultsRegion A consent rate: Specialist Requester 75.8%, Specialist Nurse in Organ Donation71.8%. Region B consent rate: Specialist Requester 71.4%, Specialist Nurse in Organ Donation 82%. Region A Specialist Requesters turned the family position from no or uncertain to support organ donation in 73% of cases, compared with 27.4% in Region B. Two Specialist Requesters in Region A were highly effective. Region B experienced problems with intervention fidelity and implementation.ConclusionsThe benefits of the Specialist Requester role remain unclear. Positive differences in consent rates achieved by Specialist Requesters in the originator region reduced over time and have yet to be successfully replicated in other regions.ImpactThe impact of Specialist Requesters on consent outcomes varied across regions and it was not known why. Specialist Requesters in Region A were better at getting family member(s) to support organ donation. In Region B, Specialist Nurse in Organ Donation consent rates were higher and problems with intervention fidelity were identified (recruitment, staffing, less experience). Policy makers need to understand it is not just a matter of waiting for the Specialist Requester intervention to work. Ongoing training and recruiting the right people with the right skills need to be addressed and consistently reviewed.
Mechanisms underlying altitudinal and horizontal range contraction: The western black crested gibbon
Authors: Yang Li , Shi Kai‐Chong , Ma Chi , Ren Guo‐Peng , Fan Peng‐Fei 
Published: November 2020

AbstractAimSpecies ranges in mountain areas may shift both horizontally and altitudinally, resulting from climate change and anthropogenic impact. Two hypotheses (the abundant centre hypothesis and the contagion hypothesis) have been proposed to account for patterns of horizontal range contraction. However, undulating topograph causes a mosaic of unsuitable habitats, which may complicate the spatial pattern of range contraction. We develop a framework incorporating horizontal and altitudinal range contraction patterns of a species living in mountain areas, to better understand the underlying mechanisms of species range contraction.LocationChina, Northern Laos and Northern VietnamTaxonWestern black crested gibbon, Nomascus concolorMethodsWe collected occurrence data of the gibbons from various sources and modelled their potential distribution range in the 1950s, 1980s and 2010s, using ecological niche modelling. We compared distances from the centre point of the potential range in the 1950s to centre points of the largest 100 patches in the 1950s and the 2010s to understand the patterns of horizontal range contraction. We also calculated potential distributions within different altitudinal ranges for six populations in each period to understand the patterns of altitudinal range contraction.ResultsPotential horizontal distribution of the gibbons decreased by 69% from the 1950s to the 2010s. The centre point of the 100 largest patches in the 2010s was further apart than in the 1950s, supporting the contagion hypothesis. No populations extended their range to higher altitude, suggesting climate change did not have a profound effect on altitudinal shifts in gibbon range. All populations lost a substantial proportion of their ranges at lower altitudes (500–1,500 m) but to different degrees, suggesting that populations experienced different anthropogenic pressures.Main conclusionsAnthropogenic threats including human population increase, agricultural expansion and hunting, were more likely than climate change to have caused range contraction in western black‐crested gibbons. This study highlights the importance of studying horizontal and altitudinal range contraction simultaneously.
A meta‐analysis of insularity effects on herbivory and plant defences
Authors: Moreira Xoaquín , Castagneyrol Bastien , García‐Verdugo Carlos , Abdala‐Roberts Luis 
Published: November 2020

AbstractAimPlants on islands are often subjected to lower levels of herbivory relative to those found at mainland sites. As a consequence, island plants are predicted to exhibit lower levels of physical or chemical defences, which renders them more susceptible to introduced herbivores. Yet, instances of high pressure by superabundant herbivores native to islands have been reported in many insular systems, which presumably would result in heightened plant defences. To date, no quantitative review has been conducted to determine how common these contrasting patterns are and their implications for the evolution of plant‐herbivore interactions.LocationIslands worldwide.TaxonPlants, insects, molluscs, mammals.MethodsWe conducted a meta‐analysis of insularity effects on herbivory and plant defences by including studies that involved island‐mainland comparisons of the same plant species in both environments (90% of cases), or insular endemics versus mainland congeners (10% of cases). We tested for differences between mammalian and invertebrate (mollusc or insect) herbivory as well as between plant chemical and physical defences by specifying comparisons based on the type of herbivore (vertebrate or invertebrate) or plant trait included in the study.ResultsMammalian herbivory was significantly higher on islands than on mainlands. In contrast, no significant effect was observed on invertebrate herbivory. In addition, we found no significant difference in either plant physical or chemical defences between insular and mainland plants, though physical defences tended to be higher for plants on islands.Main conclusionsAll analysed mammal studies focused on species introduced to islands, suggesting greater susceptibility of insular plants to exotic mammals, whereas the lack of effects in the case of invertebrate herbivory suggests no difference in susceptibility to molluscs or insects between insular and mainland plants. Interestingly, plant trait patterns suggest a trend for increased physical defences by insular plants, possibly due to heightened pressure by exotic mammalian herbivores on islands, whereas chemical defences appear uncorrelated to differences in herbivory. These findings call for further experimental and observational studies measuring defences and herbivory for multiple sympatric plant species occurring at both mainland and island sites within a system, or comparing insular endemics to congeneric mainland species.
Metformin attenuates trauma‐induced heterotopic ossification via inhibition of Bone Morphogenetic Protein signalling
Authors: Lin Hui , Shi Fuli , Jiang Shanshan , Wang Yuanyuan , Zou Junrong , Ying Ying , Huang Deqiang , Luo Lingyu , Yan Xiaohua , Luo Zhijun 
Published: November 2020

AbstractAMP‐activated protein kinase (AMPK) is an intracellular sensor of energy homoeostasis that is activated under energy stress and suppressed in energy surplus. AMPK activation leads to inhibition of anabolic processes that consume ATP. Osteogenic differentiation is a process that highly demands ATP during which AMPK is inhibited. The bone morphogenetic proteins (BMPs) signalling pathway plays an essential role in osteogenic differentiation. The present study examines the inhibitory effect of metformin on BMP signalling, osteogenic differentiation and trauma‐induced heterotopic ossification. Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3‐E1 cells, concurrent with up‐regulation of Smad6, and this effect was attenuated by knockdown of Smad6. Furthermore, we found that metformin suppressed ALP activity and mineralization of the cells, an event that was attenuated by the dominant negative mutant of AMPK and mimicked by its constitutively active mutant. Finally, administration of metformin prevented the trauma‐induced heterotopic ossification in mice. In conjuncture, AMPK activity and Smad6 and Smurf1 expression were enhanced by metformin treatment in the muscle of injured area, concurrently with the reduction of ALK2. Collectively, our study suggests that metformin prevents heterotopic ossification via activation of AMPK and subsequent up‐regulation of Smad6. Therefore, metformin could be a potential therapeutic drug for heterotopic ossification induced by traumatic injury.
PDE1 or PDE5 inhibition augments NO‐dependent hypoxic constriction of porcine coronary artery via elevating inosine 3′,5′‐cyclic monophosphate level
Authors: Nan Yan , Zeng Xueqin , Jin Zhiyi , Li Na , Chen Zhengju , Chen Jiantong , Wang Dezhong , Wang Yang , Lin Zhenlang , Ying Lei 
Published: November 2020

AbstractHypoxic coronary vasospasm may lead to myocardial ischaemia and cardiac dysfunction. Inosine 3′,5′‐cyclic monophosphate (cIMP) is a putative second messenger to mediate this pathological process. Nevertheless, it remains unclear as to whether levels of cIMP can be regulated in living tissue such as coronary artery and if so, what is the consequence of this regulation on hypoxia‐induced vasoconstriction. In the present study, we found that cIMP was a key determinant of hypoxia‐induced constriction but not that of the subsequent relaxation response in porcine coronary arteries. Subsequently, coronary arteries were treated with various phosphodiesterase (PDE) inhibitors to identify PDE types that are capable of regulating cIMP levels. We found that inhibition of PDE1 and PDE5 substantially elevated cIMP content in endothelium‐denuded coronary artery supplemented with exogenous purified cIMP. However, cGMP levels were far lower than their levels in intact coronary arteries and lower than cIMP levels measured in endothelium‐denuded coronary arteries supplemented with exogenous cIMP. The increased cIMP levels induced by PDE1 or PDE5 inhibition further led to augmented hypoxic constriction without apparently affecting the relaxation response. In intact coronary artery, PDE1 or PDE5 inhibition up‐regulated cIMP levels under hypoxic condition. Concomitantly, cGMP level increased to a comparable level. Nevertheless, the hypoxia‐mediated constriction was enhanced in this situation that was largely compromised by an even stronger inhibition of PDEs. Taken together, these data suggest that cIMP levels in coronary arteries are regulated by PDE1 and PDE5, whose inhibition at a certain level leads to increased cIMP content and enhanced hypoxic constriction.
Tsunami run‐up along the Zihuatanejo region, Mexican Pacific Coast: A modelling study
Authors: Contreras‐Tereza Víctor Kevin , Salas‐de‐León David Alberto , Monreal‐Jiménez Rosalinda , Monreal‐Gómez María Adela 
Published: November 2020

AbstractA numerical hydrodynamic model was applied to Zihuatanejo Bay on the Mexican Coast of the Pacific Ocean to study the heights and arrival times of tsunamis produced by hypothetical 7.0 and 8.0 Mw magnitude earthquakes with epicenter in the Cocos Plate, at 16.9718°N–101.973°W, as well as the flooding of Zihuatanejo Town by the tsunamis. The travel times of the tsunamis to Zihuatanejo Coast are between 18 and 19 min, maximum sea surface elevations of 1 and 10 m at the coast are estimated following a 7.0 and 8.0 Mw earthquake respectively with a tsunami inland penetration up to 400 m in the second case affecting restaurants, hotels, banks, schools, businesses, museums, and even the municipal market of the town. Therefore, a densely populated area would be affected by a tsunami triggered by an 8.0 Mw earthquake.