bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quercetin induces pro‐apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro
Authors: Guo Hengjuan , Ding Hui , Tang Xin , Liang Maoli , Li Shuo , Zhang Jing , Cao Jie 
Published: March 2021

AbstractBackgroundQuercetin, a natural flavonoid compound, is a potent cancer therapeutic agent widely found in fruit and vegetables. It has been reported to induce growth inhibition and apoptosis in both A549 and H1299 human lung cancer cells. However, the effect of quercetin‐induced autophagy on apoptosis and the possible autophagy mechanism in A549 and H1299 cells have not yet been critically examined.MethodsA549 and H1299 cells were treated with different concentrations of quercetin for 24 hours. Cell growth was measured by cell counting kit‐8 (CCK‐8) assay, whereas apoptosis was assessed by western blotting analysis of apoptotic proteins. The levels of proteins and genes involved in autophagy were determined by western blotting and reverse transcription polymerase chain reaction (RT‐PCR), respectively. Autophagosomes were also observed by transmission electron microscopy (TEM) and LC3 immunofluorescence.ResultsQuercetin inhibited cell viability and induced mitochondria‐dependent apoptosis in both A549 and H1299 cells in a dose‐dependent. Moreover, quercetin also promoted the expression of LC3‐II and beclin 1 and suppressed the expression of p62. The mRNA levels of LC3‐II, beclin 1, Atg5, Atg7, and Atg12 were upregulated by quercetin treatment. Autophagy inhibition with 3‐methyladenine could effectively inhibit quercetin‐induced apoptosis. In addition, quercetin dose‐dependently elevated the levels of SIRT1 protein and the pAMPK–AMPK ratio. Quercetin‐induced autophagy was attenuated by SIRT1 inhibitor EX527 and SirT1 knockdown by small interfering RNA (siRNA).ConclusionsQuercetin‐induced autophagy contributes to apoptosis in A549 and H1299 lung cancer cells, which involved the SIRT1/AMPK signaling pathway.
Activity of tarloxotinib‐E in cells with EGFR exon‐20 insertion mutations and mechanisms of acquired resistance
Authors: Nishino Masaya , Suda Kenichi , Koga Takamasa , Ohara Shuta , Fujino Toshio , Soh Junichi , Tirunagaru Vijaya , Vellanki Avanish , Doebele Robert C. , Mitsudomi Tetsuya 
Published: March 2021

AbstractBackgroundApproximately 10% of non‐small cell lung cancers (NSCLCs) that harbor epidermal growth factor receptor (EGFR) gene mutations have in‐frame insertions in exon 20 of the EGFR gene. These tumors do not usually respond to currently available EGFR‐tyrosine kinase inhibitors (TKIs). Tarloxotinib is a novel hypoxia‐activated prodrug that releases a potent, irreversible pan‐ERBB TKI (tarloxotinib‐E) under solid tumor hypoxia.MethodsWe examined the efficacy of tarloxotinib‐E against several types of Ba/F3 cells with introduced EGFR exon 20 mutations (EGFR A763insFQEA, V769insASV, D770insSVD, H773insH and H773insNPH mutations). We assayed growth inhibition for tarloxotinib (prodrug), tarloxotinib‐E (active form), poziotinib, afatinib, and osimertinib in Ba/F3 cells with each EGFR exon 20 mutation. We also explored acquired resistance mechanisms to tarloxotinib‐E by establishing cells with resistance to tarloxotinib‐E via chronic drug exposure after N‐ethyl‐N‐nitrosourea mutagenesis treatment.ResultsAmong all tested Ba/F3 cell lines, IC50 was ≥72.1 times higher for tarloxotinib than for tarloxotinib‐E, which implies a wide therapeutic window with this prodrug strategy. Tarloxotinib‐E was efficacious against all tested Ba/F3 cells except for H773insH, which was less sensitive to all tested EGFR‐TKIs. As acquired resistance mechanisms to tarloxotinib‐E, we identified either T790M or C797S secondary mutations, depending on the original EGFR exon 20 mutation.ConclusionsThese findings indicate that tarloxotinib‐E could be effective for NSCLC with EGFR exon 20 mutations. Our results also show that T790M or C797S mutations can confer acquired resistance to tarloxotinib‐E; and suggest that resistance mechanisms are influenced by the baseline EGFR exon 20 mutations.
Stand density of co‐existing species regulates above‐ground biomass along a local‐scale elevational gradient in tropical forests
Authors: Kunwar Suwash , Wang Li‐Qiu , Chaudhary Rajeev , Joshi Puspa Raj , Ali Arshad 
Published: March 2021

AbstractQuestions(1) Do stand density, species diversity and individual tree size variation jointly increase above‐ground biomass (AGB) along an elevational gradient? (2) How does the local‐scale elevational gradient explain the variation in AGB directly and indirectly via stand density, species diversity facet and individual tree size variation? (3) What are the main ecological mechanisms explaining variation in AGB through joint effects of stand density, species diversity and individual tree size variation along an elevational gradient in tropical forests? We hypothesized that higher stand packing, and diverse and complex stand structure drive higher AGB along a local‐scale elevational gradient in tropical forests.LocationWestern Nepal.MethodsWe analyzed biophysical tree data from 101 tropical forest plots along an elevational gradient ranging from 218 to 1,850 m above sea level. Structural equation models were applied to test the relationships among elevation, stand density, species diversity facet (either species richness, evenness, Shannon diversity or Simpson’s dominance), tree diameter and height variation, and AGB.ResultsStand density increased but species diversity declined AGB, whereas tree diameter and height variation did not strongly influence AGB. The indirect effects of stand density, species diversity facet, and tree diameter and height variation on AGB via each other were non‐significant. Elevation reduced stand density, species richness and AGB but increased tree height variation, and hence, the indirect effects of elevation on AGB were variable. These results suggest that competitive exclusion or selection or environmental filtering effects are shaping the species diversity, structural complexity and AGB of the studied tropical forests.ConclusionsWe argue that compact stand density, rather than diversity and individual tree size variation, of co‐existing species is important for higher AGB but higher species diversity and stand structural complexity may need to be considered in the context of biodiversity conservation and forest management.
On the profitability of self‐sabotage
Authors: Brown David P. , Sappington David E. M. 
Published: March 2021

AbstractWe demonstrate how a supplier can enhance his expected profit by intentionally increasing his expected production costs or limiting his ability to reduce these costs. Such self‐sabotage benefits the supplier when it induces a buyer to implement a more favourable procurement policy, i.e., one that motivates the supplier to deliver cost‐reducing effort systematically rather than selectively. We also demonstrate how the seemingly inefficient persistent implementation of a procurement contract that does not change as the prevailing environment changes can reduce procurement costs by deterring self‐sabotage.
Self‐Supervised Learning of Part Mobility from Point Cloud Sequence
Authors: Shi Yahao , Cao Xinyu , Zhou Bin 
Published: March 2021

AbstractPart mobility analysis is a significant aspect required to achieve a functional understanding of 3D objects. It would be natural to obtain part mobility from the continuous part motion of 3D objects. In this study, we introduce a self‐supervised method for segmenting motion parts and predicting their motion attributes from a point cloud sequence representing a dynamic object. To sufficiently utilize spatiotemporal information from the point cloud sequence, we generate trajectories by using correlations among successive frames of the sequence instead of directly processing the point clouds. We propose a novel neural network architecture called PointRNN to learn feature representations of trajectories along with their part rigid motions. We evaluate our method on various tasks including motion part segmentation, motion axis prediction and motion range estimation. The results demon strate that our method outperforms previous techniques on both synthetic and real datasets. Moreover, our method has the ability to generalize to new and unseen objects. It is important to emphasize that it is not required to know any prior shape structure, prior shape category information or shape orientation. To the best of our knowledge, this is the first study on deep learning to extract part mobility from point cloud sequence of a dynamic object.
On the NH and CH acidities of toluidine isomers: theoretical description and practical consequences for the synthesis of certain aniline dyes
Authors: Lukeš Vladimír , Hartmann Horst 
Published: March 2021

AbstractFor the toluidine isomers, amino group acidity represents a characteristic feature of these compounds in their electric neutral state. As demonstrated by theoretical calculations based on the quantum chemistry composite G4 method and density functional theory, the CH acidity of the methyl group is hidden under NH acidity. The transformation of toluidines into their mono‐ and bi‐oxidised states significantly increases the acidity of the methyl group. This study indicates that the presence or absence of these deprotonated species in reaction mixtures will determine the CN or CC coupling toluidine products. In agreement with published synthetic approaches for aniline dyes, such as mauveine and fuchsine, the results obtained explain the alternative reaction pathways occurring during the oxidation of toluidine isomers.
Hereditäre Ichthyose und Pilzinfektion: aktuelle Daten zu Pathogenese und Behandlungsstrategien
Authors: Miao Huilei , Dong Ruijia , Zhang Shiyu , Yang Lu , Liu Yuehua , Wang Tao 
Published: March 2021

ZusammenfassungHereditäre Ichthyosen sind eine Gruppe von Genodermatosen, die entweder als nichtsyndromal oder syndromal klassifiziert werden. Nichtsyndromale Ichthyosen und das Keratitis‐Ichthyosis‐Taubheitssyndrom (keratitis, ichthyosis and deafness syndrome, KID‐Syndrom) prädisponieren für Pilzinfektionen. Diagnostik und Behandlung von Pilzinfektionen bei Ichthyosen sind herausfordernd. In dieser Übersicht fassen wir publizierte Ichthyose‐Fälle mit Pilzinfektion aus den letzten 50 Jahren zusammen. Bei Patienten mit Ichthyose in Kombination mit Pilzinfektion traten atypische Manifestationen wie Alopezie, Papeln und brüchige Nägel auf. Verschiedene Pathomechanismen wurden vorgeschlagen, darunter Mutationen Ichthyose‐relevanter Gene, die über verschiedene Signalwege zur Störung der Hautbarriere führen. Erkrankungen des Immunsystems, wie Atopie oder Störungen der angeborenen Immunität, tragen ebenfalls zur Anfälligkeit bei. Bestimmte Pilze können die Immunabwehr umgehen. Ausgedehnte und wiederkehrende Pilzinfektionen sind bei Ichthyose‐Patienten nicht selten, was die Heilung erschwert und systemische antimykotische Therapien erfordert. Etablierte und neue Ichthyosebehandlungen zielen darauf ab, die Barrierefunktion der Haut zur Vermeidung von Pilzinfektionen zu verbessern. Daher ist der enge Zusammenhang zwischen Ichthyose und Pilzinfektionen in der klinischen Praxis von entscheidender Bedeutung und erfordert ärztlicherseits mehr Aufmerksamkeit. Weitere Studien sind erforderlich, um beteiligte Mechanismen und sinnvolle Behandlungsstrategien zu erforschen.
Sodium‐glucose co‐transporter‐2 inhibitors for the prevention of cardiorenal outcomes in type 2 diabetes: An updated meta‐analysis
Authors: Giugliano Dario , Longo Miriam , Caruso Paola , Maiorino Maria Ida , Bellastella Giuseppe , Esposito Katherine 
Published: March 2021

AbstractA meta‐analysis of cardiorenal outcomes of sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) available in Europe or the United States in patients with type 2 diabetes (T2D) is presented. An electronic search up to 6 January 2021 was conducted to determine eligible trials. A total of eight cardiorenal outcomes trials of SGLT‐2is (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) were identified, with 65,587 patients. Data were analysed using a random effects model. Overall, SGLT‐2is were associated with a 12% reduced risk of major adverse cardiovascular events (MACE; HR = 0.88; 95% CI, 0.83–0.93; Q statistic, p = .19), with no significant heterogeneity (p for interaction = .465) between subgroups of patients with or without cardiovascular disease (CVD). The risk of the composite renal outcome was significantly reduced by treatment with SGLT‐2is (HR = 0.61, 95% CI, 0.54–0.70), with no significant heterogeneity of associations with outcome (I2 = 37%, p = .11), and no difference in the risk between patients with or without CVD (p for interaction = .665). SGLT‐2is have moderate benefits on MACE and major benefits on the progression of diabetic kidney disease.
Clinical and echocardiographic predictors of decompensation in acute severe aortic regurgitation due to infective endocarditis
Authors: Chasapi Athina , Mbonye Kamatamu A. , Bajomo Omotomilola , Young William J. , Primus Christopher , Ambekar Shirish , Wong Kit , Uppal Rakesh , Davies Lewis Ceri , Khanji Mohammed Y. , Woldman Simon , Lloyd Guy , Bhattacharyya Sanjeev 
Published: March 2021

AbstractBackgroundPatients with acute severe aortic regurgitation (AR) due to infective endocarditis can progress rapidly from the hemodynamically stable patient to pulmonary edema and cardiogenic shock. We sought to identify patients at risk of decompensation where emergent surgery should be undertaken.MethodsWe identified 90 patients with acute severe AR from the echocardiography laboratory database. Baseline clinical, hemodynamic (heart rate (HR) and blood pressure (BP)), and echocardiographic data including mitral filling, premature mitral valve closure (PMVC), and diastolic mitral regurgitation (DMR) were identified. The primary endpoint was subsequent development of pulmonary edema or severe hemodynamic instability.ResultsPatients who met the primary endpoint had a higher HR (98.5 bpm vs 80.5 bpm), lower diastolic BP (54 mm Hg vs 61.5 mm Hg), higher mitral E‐wave velocity (113 cm/s vs 83 cm/s), higher E/e′ ratio (12.4 vs 8), higher proportion of DMR (27.8% vs 7.4%), and PMVC (25% vs 9.3%) than patients who did not meet the endpoint. The proportion of patients with the primary endpoint increased as HR increased ((≤81 bpm) 3/30 (10%), (81–94 bpm) 11/31 (35.5%), (≥94 bpm) 22/29 (75.9%), P < .0001) and as the diastolic BP reduced ((≤54 mm Hg) 19/31 (61.3%), (54–63 mm Hg) 12/31 (38.7%), (≥63 mm Hg) 5/28 (17.9%), P = .003). Independent predictors were a higher HR (OR 1.08 (95% CI 1.04–1.13) P = .0003) and DMR (OR 4.71 (95% CI 1.23–18.09), P = .02).ConclusionDecompensation in acute severe AR is common. Independent predictors of decompensation are increasing HR(≥94 bpm) and the presence of DMR. Those with these adverse markers should be considered for emergent surgery.
Biological traits of seabirds predict extinction risk and vulnerability to anthropogenic threats
Authors: Richards Cerren , Cooke Robert S. C. , Bates Amanda E. 
Published: March 2021

ABSTRACTAimSeabirds are heavily threatened by anthropogenic activities, and their conservation status is deteriorating rapidly. Nonetheless, these pressures are unlikely to impact all species uniformly. It remains an open question whether seabirds with similar ecological roles are responding similarly to human pressures. Our aims were as follows: (a) to test whether threatened versus non‐threatened seabirds are separated in trait space; (b) to quantify the similarity of species' roles (redundancy) per IUCN Red List Category; and (c) to identify traits that render species vulnerable to anthropogenic threats.LocationGlobal.Time periodContemporary.Major taxa studiedSeabirds.MethodsWe compile and impute eight traits that relate to species' vulnerabilities and ecosystem functioning across 341 seabird species. Using these traits, we build a mixed‐data principal component analysis of species' trait space. We quantify trait redundancy using the unique trait combinations (UTCs) approach. Finally, we undertake a similarity of percentages analysis to identify which traits explain the greatest difference between threat groups.ResultsWe find that seabirds segregate in trait space based on IUCN threat status, indicating that anthropogenic impacts are selectively removing large, long‐lived, pelagic surface feeders with narrow habitat breadths. We also find that threatened species have higher trait redundancy, whereas non‐threatened species have relatively limited redundancy. Finally, we find that species with narrow habitat breadths, fast reproductive speeds and varied diets are more likely to be threatened by habitat‐modifying processes (e.g., pollution and natural system modifications), whereas pelagic specialists with slow reproductive speeds and varied diets are vulnerable to threats that directly impact survival and fecundity (e.g., invasive species and biological resource use) and climate change. Species with no threats are non‐pelagic specialists with invertebrate diets and fast reproductive speeds.Main conclusionsOur results suggest that both threatened and non‐threatened species contribute unique ecological strategies. Consequently, conserving both threat groups, but importantly with contrasting approaches, might avoid potential changes in ecosystem functioning and stability.
Sustaining a career in general practice: Embodied work, inequality regimes, and turnover intentions of women working in general practice
Authors: Mayson Susan , Bardoel Anne 
Published: March 2021

AbstractThe medical workforce in Australia is rapidly feminizing, with general practice (GP) seen as an attractive career choice for female doctors looking for greater work flexibility. However, there is evidence of increased female GP turnover, particularly among younger GPs. Drawing on interviews with a sample of 26 Australian female GPs, this study explores how the embodied nature of GP work and gendered organizational processes create inequality regimes founded on gendered normative expectations of GP work, leading to turnover intentions. Then, considering the literature on job crafting, we problematize the notion of employees proactively optimizing their work environment to show how some female GPs work within gender constraints to craft a sustainable medical career, with others failing. These findings contribute to our understanding of the embodied nature of work and as such may better inform both individual decisions and workforce planning policy to reduce GP turnover and sustain Australia's medical workforce.
Limited understanding of bushfire impacts on Australian invertebrates
Authors: Saunders Manu E. , Barton Philip S. , Bickerstaff James R. M. , Frost Lindsey , Latty Tanya , Lessard Bryan D. , Lowe Elizabeth C. , Rodriguez Juanita , White Thomas E. , Umbers Kate D. L. 
Published: March 2021

Abstract
Understanding how increasing risk of frequent and severe fires affects biodiversity and ecosystem function is important for effective conservation and recovery, but large knowledge gaps exist for many taxa in many parts of the world, especially invertebrates.
After Australia's 2019–2020 catastrophic bushfire disaster, estimates of biodiversity loss and government priorities for post‐fire conservation activities were focused on vertebrates and plants because of lack of knowledge about invertebrates.
Our synthesis of published evidence reveals a fragmented and ambiguous body of literature on invertebrate responses to fire in Australian ecosystems, limiting the capacity of evidence to inform effective conservation policy in response to extreme fire events. Peer‐reviewed studies are available for only six of the more than 30 invertebrate phyla and 88% were on arthropods, predominantly ants.
Nearly all studies (94%) were conducted in terrestrial habitats, with only four studies measuring impacts in freshwater habitats and no studies of impacts on marine invertebrates. The high variation in study designs and treatment categories, as well as the absence of key methodological details in many older observational studies, means that there is substantial opportunity to improve our approach to collating meaningful estimates of general fire effects.
To understand the full ecological effects of catastrophic fire events, and design effective policies that support recovery of ecosystems now and in future, it is critical that we improve understanding of how fire regimes affect invertebrates. We list key priorities for research and policy to support invertebrate conservation and ecosystem recovery in the face of increasing fire risk.
Diverse bacterial profile in extraradicular biofilms and periradicular lesions associated with persistent apical periodontitis
Authors: Zhang C. , Yang Z. , Hou B. 
Published: March 2021

AbstractAimTo characterize the bacterial community present in the extraradicular biofilm and periradicular lesions associated with persistent apical periodontitis.MethodologyEighteen adult patients who presented with persistent periradicular lesions after root canal treatment and scheduled for endodontic surgery were selected. During surgery, extraradicular samples of biofilms and periradicular lesions were collected. Ten pairs of periradicular lesions and extraradicular biofilm samples were randomly selected for ribosomal 16S rRNA cloning and sequencing. A Wilcoxon’s rank‐sum test was used to compare total bacterial counts and the levels of individual genera and species between the two groups (P < 0.05).ResultsOverall, seventy‐three phylotypes belonging to six different phyla were identified from 1000 sequenced clones. Mogibacterium timidum, Streptococcus intermedius and Enterococcus faecalis predominated in both extraradicular biofilm and periapical lesions. Propionibacterium propionicus, Abiotrophia adiacens, Peptostreptococcus prevotii, Campylobacter gracilis and Pseudomonas aeruginosa were found in significantly higher levels in the extraradicular biofilm than periapical lesions, whilst Parvimonas micra and Atopobium rimae were more abundant in periapical lesions (P < 0.05).ConclusionsThe microbial profile of extraradicular biofilms differed from periapical lesions, indicating the presence of diverse bacterial populations in these regions. Several genera and species were significantly associated with the formation of extraradicular biofilms.