bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK4/6 inhibitor palbociclib overcomes acquired resistance to third‐generation EGFR inhibitor osimertinib in non‐small cell lung cancer (NSCLC)
Authors: Qin Qiong , Li Xiaoqing , Liang Xingmei , Zeng Lili , Wang Jing , Sun Linlin , Zhong Diansheng 
Published: July 2020

BackgroundThe third‐generation EGFR‐TKI, represented by osimertinib, has been widely used in clinical practice; however, resistance eventually emerges. At present, it remains unclear whether an abnormal cell cycle is involved in acquired resistance, and whether the combination of palbociclib (CDK4/6 inhibitor) and osimertinib can overcome the third‐generation TKI resistance.MethodsWe established osimertinib‐resistant cells (H1975 OR) derived from EGFR‐mutant NSCLC cells H1975. Drug effects on cells were assessed with Cell Counting Kit‐8 (CCK8). Protein alterations were detected with western blot analysis. RT‐PCR was used to evaluate the differences of gene mRNA. Cell cycle distribution of H1975 S and H1975 OR cells was compared using flow cytometry.ResultsCompared with H1975, the sensitivity of H1975OR to the CDK4/6 inhibitor was increased and the proportion of cells in G1 phase was decreased. The mRNA level of CDK4, CDK 6 and the protein level of CDK4, pRB were increased in H1975OR. In the H1975OR cells, palbociclib significantly increased the proportion of G1 phase cells. The combination of osimertinib and palbociclib synergistically decreased the survival of H1975OR by cell cycle arrest. Combined treatment was found to inhibit the initial phosphorylation of RB by inhibiting the function of CDK4/6, significantly reducing the level of p‐RB, and blocking cell proliferation.ConclusionsAn osimertinib acquired resistance cell line (H1975 OR) was successfully established. The expression of cell cycle related genes was altered in H1975OR. The expression of CDK4 and the phosphorylation of Rb, the downstream molecule of CDK4/6, was increased in H1975OR cells. The combination of CDK4/6 inhibitor palbociclib and osimertinib could overcome the acquired resistance of osimertinib.
ntbox: An r package with graphical user interface for modelling and evaluating multidimensional ecological niches
Authors: Osorio‐Olvera Luis , Lira‐Noriega Andrés , Soberón Jorge , Peterson Andrew Townsend , Falconi Manuel , Contreras‐Díaz Rusby G. , Martínez‐Meyer Enrique , Barve Vijay , Barve Narayani 
Published: July 2020

Abstract

Biodiversity studies rely heavily on estimates of species' distributions often obtained through ecological niche modelling. Numerous software packages exist that allow users to model ecological niches using machine learning and statistical methods. However, no existing package with a graphical user interface allows users to perform model calibration and selection based on convex forms such as ellipsoids, which may match fundamental ecological niche shapes better, incorporating tools for exploring, modelling, and evaluating niches and distributions that are intuitive for both novice and proficient users.

Here we describe an r package, NicheToolBox (ntbox), that allows users to conduct all processing steps involved in ecological niche modelling: downloading and curating occurrence data, obtaining and transforming environmental data layers, selecting environmental variables, exploring relationships between geographic and environmental spaces, calibrating and selecting ellipsoid models, evaluating models using binomial and partial ROC tests, assessing extrapolation risk, and performing geographic information system operations via a graphical user interface. A summary of the entire workflow is produced for use as a stand‐alone algorithm or as part of research reports.

The method is explained in detail and tested via modelling the threatened feline species Leopardus wiedii. Georeferenced occurrence data for this species are queried to display both point occurrences and the IUCN extent of occurrence polygon (IUCN, 2007). This information is used to illustrate tools available for accessing, processing and exploring biodiversity data (e.g. number of occurrences and chronology of collecting) and transforming environmental data (e.g. a summary PCA for 19 bioclimatic layers). Visualizations of three‐dimensional ecological niches modelled as minimum volume ellipsoids are developed with ancillary statistics. This niche model is then projected to geographic space, to represent a corresponding potential suitability map.

Using ntbox allows a fast and straightforward means by which to retrieve and manipulate occurrence and environmental data, which can then be implemented in model calibration, projection and evaluation for assessing distributions of species in geographic space and their corresponding environmental combinations.
Resting Borg score as a predictor of safe discharge of chronic obstructive pulmonary disease from the emergency department observation unit
Authors: Sengupta Ruchira , Loftus Timothy M. , Doers Matthew , Jandarov Roman A. , Phillips Michael , Ko Jonathan , Panos Ralph J. , Zafar Muhammad A. 
Published: July 2020

AbstractBackgroundChronic obstructive pulmonary disease exacerbations (eCOPD) can be life‐threatening and costly. Emergency department (ED) observation units (ED‐Obs) offer short‐term care to safely reduce preventable hospitalizations. Accurately identifying eCOPD patients who can be discharged safely will improve outcomes.ObjectivesThe objective were to: I) evaluate utility of conventional clinical variables as predictors of safe discharge and II) assess utility of serial resting Borg score and novel Dyspnea Assessment Score (DAS) for identifying eCOPD patients who can be safely discharged from ED‐Obs.MethodsThis study was carried out in a 680‐bed tertiary, academic hospital with >700 annual eCOPD ED encounters and a 16‐bed ED‐Obs. A two‐phase study of eCOPD patients admitted to ED‐Obs was performed. Objective I was a retrospective study including all eCOPD admits from April 2016 to May 2017. Predictor variables (demographics, COPD severity, comorbid conditions, exacerbation severity, clinical care in ED) and outcome variables (ED‐Obs disposition, ED revisits) were obtained through electronic medical records. Safe discharge was defined as home disposition from ED‐Obs without 7‐day revisit. A stepwise regression was performed for predictors of safe discharge. Objective II was a prospective observation study for change in every 4‐hour serial resting Borg score and DAS as identifiers of safe discharge. Comparative and receiver operating characteristic (ROC) analyses were performed. A p‐value of <0.05 was considered significant.ResultsIn Objective I, 171 patients with age, FEV1%, and body mass index of 59.8 (±9.5) years, 35 (±24)%, and 28.8 (±8) m2/kg were included. After ED‐Obs treatment 78 (45.6%) were hospitalized and 93 (54.4%) were discharged home, of whom 11 (6.4%) had 7‐day ED revisit. Safe discharge occurred in 82 (48%). None of the predictor variables correlated with safe discharge. In Objective II, of 38 patients included, 20 (52.6%) had safe discharge. Among others, 16 (42%) were hospitalized and two (5.2%) had 7‐day ED revisit. The admission Borg scores and DASs were similar in both groups. The predisposition Borg score was significantly lower in patients with safe discharge (2.75 vs. 5.28, p < 0.001) and had the highest area under curve on ROC (0.77) for safe discharge. DAS was not significantly different between groups.ConclusionsRoutine clinical variables do not identify eCOPD patients who can be safely discharged from ED‐Obs. Change in resting Borg score during the course of ED‐Obs treatment safely identifies patients for discharge. Prospective, external validation is needed to incorporate serial Borg scores in ED‐Obs disposition decision for improved safety.
Remineralization and fluoride uptake of white spot lesions under dental varnishes
Authors: Shen P , McKeever A , Walker GD , Yuan Y , Reynolds C , Fernando JR , Chen Y‐Y , MacRae CM , Schneider P , Reynolds EC 
Published: July 2020

AbstractIntroductionThe aim of this study was to evaluate white spot lesion (WSL) remineralization and fluoride uptake by the application of fluoride varnishes directly onto artificial WSLs in vitro.MethodsMI varnish containing casein phosphopeptide–amorphous calcium phosphate (CPP‐ACP) and 2.26% fluoride and Duraphat varnish containing 2.26% fluoride (no added calcium) were compared with a placebo varnish (no added calcium or fluoride). Two WSLs were prepared in enamel slabs and varnish applied to cover one of the two lesions. Each slab was immersed in artificial saliva for 14 days at 37°C. Mineral content was determined using transverse microradiography and fluoride uptake using electron probe microanalysis. The data were statistically analysed using a linear mixed model.ResultsBoth MI and Duraphat varnishes significantly remineralized the covered and uncovered WSLs when compared with the placebo varnish (P < 0.001). The WSLs covered with varnish showed greater remineralization than those uncovered. MI varnish produced the highest level of remineralization and significantly greater fluoride uptake (0.44 ± 0.08 wt%) compared with Duraphat (0.24 ± 0.03 wt%) and the placebo varnish (0.06 ± 0.05 wt%).ConclusionVarnish containing fluoride and CPP‐ACP was superior to varnish containing fluoride alone in promoting WSL remineralization and fluoride uptake.
Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice
Authors: Wu Jingfang , Dong Xinran , Li Wen , Zhao Liping , Zhou Li , Sun Shan , Li Huawei 
Published: July 2020

AbstractObjectivesTo investigate the role of dibenzazepine (DBZ) in promoting supporting cell (SC) proliferation and hair cell (HC) regeneration in the inner ear.Materials and MethodsPostnatal day 1 wild‐type or neomycin‐damaged mouse cochleae were cultured with DBZ. Immunohistochemistry and scanning electron microscopy were used to examine the morphology of cochlear cells, and high‐throughput RNA‐sequencing was used to measure gene expression levels.ResultsWe found that DBZ promoted SC proliferation and HC regeneration in a dose‐dependent manner in both normal and damaged cochleae. In addition, most of the newly regenerated HCs induced by DBZ had visible and relatively mature stereocilia bundle structures. Finally, RNA sequencing detected the differentially expressed genes between DBZ treatment and controls, and interaction networks were constructed for the most highly differentially expressed genes.ConclusionsOur study demonstrates that DBZ can significantly promote SC proliferation and increase the number of mitotically regenerated HCs with relatively mature stereocilia bundles in the neonatal mouse cochlea by inhibiting Notch signalling and activating Wnt signalling, suggesting the DBZ might be a new therapeutic target for stimulating HC regeneration.
Under adverse conditions, older small tree finch males (Camarhynchus parvulus) produce more offspring than younger males
Authors: Wappl Christian , Cimadom Arno , Filek Nikolaus , Heyer Eileen , Tebbich Sabine 
Published: July 2020

AbstractFemales of many bird species prefer mating with older males, presumably because they provide superior parental care and possibly superior genes. A previous study found that female small tree finches (Camarhynchus parvulus) preferred pairing with old males and had a higher breeding success when paired with old males because their nests were more concealed, higher up in the canopy and therefore less likely to be depredated. However, causes for brood loss have changed over the last decade: predation of small tree finch nests has decreased, whereas brood losses due to parasitism by the invasive parasitic fly Philornis downsi have increased. In the present study, we investigated (a) how the change in predation and parasitism by P. downsi influenced the breeding success of small tree finches, (b) whether there were still differences in breeding success between young and old males, (c) whether P. downsi infestation had a differential effect on nests of young and old males and (d) whether young and old males differed in foraging success. During 2012–2016, we found an overall low influence of predation and a high influence of P. downsi, but neither differed between nests of young and old males. Nests of old males had more fledglings than those of young males. However, the difference in breeding success disappeared when P. downsi numbers were experimentally reduced by injecting an insecticide into nests. This indicates that older males were able to compensate for the detrimental effects of parasitism.
Hiatal hernia with focal megaoesophagus in a Friesian stallion
Authors: Lehman M. , Hendrickson D. , Selberg K. 
Published: July 2020

SummaryHiatal hernia with focal megaoesophagus was diagnosed in a 10‐year‐old Friesian stallion presenting to the referral hospital for further investigation of recurrent oesophageal obstruction. Oesophageal endoscopy revealed dilation of the distal oesophagus with alterations in the mucosa characteristic of gastric mucosa in the distal oesophagus. In addition, a moderate amount of feed material was identified in the distal oesophagus. Positive contrast radiography showed that approximately half of the stomach was herniated cranially through the diaphragm. Management of the disease included recommendations to elevate the patient’s torso during feeding and provide mash‐only feeds. Provided that successful control of the megaoesophagus could be achieved, surgical repair of the hiatal hernia may be an option for the future. This is the first report of hiatal herniation in horses. We report the successful conservative management of a stallion with both megaoesophagus and hiatal herniation through elevated feedings and selective exercise management.
R‐hydroxynitrile lyase from the cyanogenic millipede, Chamberlinius hualienensis—A new entry to the carrier protein family Lipocalines
Authors: Motojima Fumihiro , Izumi Atsushi , Nuylert Aem , Zhai Zhenyu , Dadashipour Mohammad , Shichida Sayaka , Yamaguchi Takuya , Nakano Shogo , Asano Yasuhisa 
Published: July 2020

Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrin into cyanide and the corresponding aldehyde or ketone. Moreover, they catalyze the synthesis of cyanohydrin in the reverse reaction, utilized in industry for preparation of enantiomeric pure pharmaceutical ingredients and fine chemicals. We discovered a new HNL from the cyanogenic millipede, Chamberlinius hualienensis. The enzyme displays several features including a new primary structure, high stability, and the highest specific activity in (R)‐mandelonitrile ((R)‐MAN) synthesis (7420 U·mg−1) among the reported HNLs. In this study, we elucidated the crystal structure and reaction mechanism of natural ChuaHNL in ligand‐free form and its complexes with acetate, cyanide ion, and inhibitors (thiocyanate or iodoacetate) at 1.6, 1.5, 2.1, 1.55, and 1.55 Å resolutions, respectively. The structure of ChuaHNL revealed that it belongs to the lipocalin superfamily, despite low amino acid sequence identity. The docking model of (R)‐MAN with ChuaHNL suggested that the hydroxyl group forms hydrogen bonds with R38 and K117, and the nitrile group forms hydrogen bonds with R38 and Y103. The mutational analysis showed the importance of these residues in the enzymatic reaction. From these results, we propose that K117 acts as a base to abstract a proton from the hydroxyl group of cyanohydrins and R38 acts as an acid to donate a proton to the cyanide ion during the cleavage reaction of cyanohydrins. The reverse mechanism would occur during the cyanohydrin synthesis. (Photo: Dr. Yuko Ishida)DatabasesStructural data are available in PDB database under the accession numbers 6JHC, 6KFA, 6KFB, 6KFC, and 6KFD.
Temperature and precipitation at migratory grounds influence demographic trends of an Arctic‐breeding bird
Authors: Doyle Susan , Cabot David , Walsh Alyn , Inger Richard , Bearhop Stuart , McMahon Barry J. 
Published: July 2020

AbstractAnthropogenic climate disruption, including temperature and precipitation regime shifts, has been linked to animal population declines since the mid‐20th century. However, some species, such as Arctic‐breeding geese, have thrived during this period. An increased understanding of how climate disruption might link to demographic rates in thriving species is an important perspective in quantifying the impact of anthropogenic climate disruption on the global state of nature. The Greenland barnacle goose (Branta leucopsis) population has increased tenfold in abundance since the mid‐20th century. A concurrent weather regime shift towards warmer, wetter conditions occurred throughout its range in Greenland (breeding), Ireland and Scotland (wintering) and Iceland (spring and autumn staging). The aim of this study was to determine the relationship between weather and demographic rates of Greenland barnacle geese to discern the role of climate shifts in the population trend. We quantified the relationship between temperature and precipitation and Greenland barnacle goose survival and productivity over a 50 year period from 1968 to 2018. We detected significant positive relationships between warmer, wetter conditions on the Icelandic spring staging grounds and survival. We also detected contrasting relationships between warmer, wetter conditions during autumn staging and survival and productivity, with warm, dry conditions being the most favourable for productivity. Survival increased in the latter part of the study period, supporting the possibility that spring weather regime shifts contributed to the increasing population trend. This may be related to improved forage resources, as warming air temperatures have been shown to improve survival rates in several other Arctic and northern terrestrial herbivorous species through indirect bottom‐up effects on forage availability.
Fungal endophyte diversity in Paspalum and effects on plant growth
Authors: Depetris Mara B. , Acuña Carlos A. , Gutierrez Susana , Marcón Florencia , Felitti Silvina A. 
Published: July 2020

AbstractIn natural ecosystems, plants appear to be in symbiosis with diverse fungal endophytes which can have impacts on plant communities. Paspalum is one of the most important grass genera in South American grasslands. The aim of this work was to determine the presence of fungal endophytes in two Paspalum species and evaluate their effects on plant growth. Sixty plant samples were collected for Paspalum notatum in a rangeland in northeastern Argentina, and the same number for Paspalum dilatatum in central Argentina. A triple‐sterilization process was carried out by submerging small pieces of leaves and stems for the isolation of fungi from the collected plants. In order to identify endophytes, morphological characters and fungal sequences corresponding to the ITS (Internal Transcribed Spacer) region were analysed. A total of eight genera were identified: Acremonium, Alternaria, Aspergillus, Bipolaris, Cladosporium, Fusarium, Penicillium and Trichoderma. A greenhouse trial was conducted to determine the effects of fungal endophytes on growth. Trichoderma significantly increased relative chlorophyll content in P. notatum and Acremonium endophytes increased tiller number, and above‐ and below‐ground biomass in P. dilatatum. The diversity of fungal endophytes that was present in P. notatum and P. dilatatum was described. In conclusion, some aspects of growth of these Paspalum species seem to be positively affected by Trichoderma and Acremonium.
Effects of cryoprotectants on Nostoc sphaeroides superchilled at low temperature (−3.0°C) and their action mechanisms
Authors: Wu Xiao‐Fei , Zhang Min , Sun Yanan , Bhandari Bhesh , Fan Dongcui 
Published: July 2020

AbstractEffects of cryoprotectants (NaCl, sucrose and trehalose) on Nostoc sphaeroides (N. sphaeroides) superchilled at −3.0°C as well as their action mechanisms were studied. Prior to storage, N. sphaeroides were immersed into different concentrations (5% and 10%) of NaCl solutions, sucrose solutions, and trehalose solutions for 2 hr. The texture properties, drip loss and low field nuclear magnetic resonance (NMR)‐imaging of N. sphaeroides with different treatments were evaluated. The freezing point, solute absorption, water distribution and microscopic structure were also measured to illustrate the action mechanisms of cryoprotectants. Results suggested that cryoprotectants offered an effective method for keeping the texture properties, lowering drip loss, and maintaining the shape of N. sphaeroides. Among all the cryoprotectants used, 5% NaCl exhibited the best effect. The study of their action mechanisms showed that cryoprotectants were efficient in reducing the freezing point, the proportion of free water and microscopic structure destruction of N. sphaeroides.Practical ApplicationsConsidering the higher water content of N. sphaeroides, it is not suitable to be deeply frozen because the formation of numerous ice crystals can cause severe damages to the tissue. To suppress these undesirable changes in superchilling, cryoprotectants including NaCl, sucrose and trehalose are added to the food products. This research contributes to lay a theoretical foundation for the further study of superchilling storage of N. sphaeroides.
The physiochemical and preservation properties of fish sarcoplasmic protein/chitosan composite films containing ginger essential oil emulsions
Authors: Cai Luyun , Wang Yaru , Cao Ailing 
Published: July 2020

AbstractActive films with essential oils have attracted more attention in recent years. In order to improve the solubility and stability of ginger essential oil (GEO) in film forming solutions, GEO coarse emulsion and nanoemulsions were prepared named CGEO (z‐average = 799.53 nm), NGEO‐1 (z‐average = 114.71 nm) and NGEO‐2 (z‐average = 59.30 nm), respectively. And the effect of concentration (0.5% and 1.0% v/v) and particle sizes of GEO emulsions on the physiochemical and preservation properties of fish sarcoplasmic protein and chitosan blend based edible films were studied in this study. The elongation at break significantly (p < .05) increased after adding GEO emulsions, and the light transmittance, water vapor permeability and water solubility were the lowest when NGEO‐2 was incorporated into films. The antioxidant and antimicrobial activities of films were concentration‐dependent. Furthermore, all the films were applied into packaging red sea breams fillets, and the results of total viable counts, pH and thiobarbituric acid demonstrated that SP‐CH films with GEO emulsions, especially nanoemulsions obviously prolonged the shelf‐life of fillets during 4°C.Practical ApplicationsIn recent years, the research about incorporating essential oils into edible films to prepare active edible films due to their antimicrobial and antioxidant properties have been more documented. In this study, fish sarcoplasmic protein and chitosan were chosen as film‐forming materials to prepare active films with ginger essential oil emulsions. The physicochemical, mechanical, optical properties of films showed that the films have the basic characteristics as food packaging materials. The releasing and antioxidant property of films indicated that the active films have a potential application in packaging food which was easy oxidized. The basic properties of films combined with oxidation indicators (total viable count, pH and thiobarbituric acid reactive substances) would provide the scientific basis for developing active films and their application for food packaging, such as seafood, meat, fruits and vegetables.