bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of small cell lung cancer metastases: Organ specificity and timing
Authors: Megyesfalvi Zsolt , Tallosy Bernadett , Pipek Orsolya , Fillinger Janos , Lang Christian , Klikovits Thomas , Schwendenwein Anna , Hoda Mir Alireza , Renyi‐Vamos Ferenc , Laszlo Viktoria , Rezeli Melinda , Moldvay Judit , Dome Balazs 
Published: February 2021

AbstractBackgroundEarly metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood‐borne metastases in a comprehensive large cohort of SCLC patients.MethodsIn this retrospective non‐interventional cross‐sectional study of 1009 Caucasian SCLC patients, we investigated the correlation between the distinct locations of the primary tumor and metastatic sites.ResultsThe onset of bone (p < 0.001), brain (p < 0.001), and pericardial (p = 0.02) metastases were late events, whereas adrenal gland (p = 0.005) and liver (p < 0.001) metastases occurred earlier. No significant difference was found in the distribution of early versus late metastases when comparing central and peripheral primary tumors. Patients with bone metastases had a higher than expected likelihood of having liver metastases, while brain metastases tended to appear together with adrenal gland metastases. Pleural and both lung and pericardial metastases also tended to co‐metastasize together more frequently than expected if metastatic events occurred independently. Notably, patients with central primary tumors had decreased median overall survival (OS) compared to those with peripheral tumors, although this tendency does not appear to be significant (p = 0.072).ConclusionOur results are suggestive for particular site‐ and sequence‐specific metastasis patterns in human SCLC. SCLC bone metastases tend to appear together with liver metastases, while brain metastases occur together with adrenal gland metastases. Better understanding of metastasis distribution patterns might help to improve the diagnosis and therapeutic decision‐making in SCLC patients.
MicroRNA‐210 targets FBXO31 to inhibit tumor progression and regulates the Wnt/β‐catenin signaling pathway and EMT in esophageal squamous cell carcinoma
Authors: Meng Jing , Zhang Chao , Zhao Tongquan , Shi Guangwen , Zhao Jingjing , Lin Zhaoxia 
Published: February 2021

AbstractEvidence from previous studies showed that the dysregulation of microRNA (miR) is frequently associated with tumor progression. The aberrant miR‐210 expression has been identified in a variety of tumors. However, its biological roles in esophageal squamous cell carcinoma (ESCC) still need further elucidation. Thus, in the current study we explore the roles of miR‐210 in ESCC progression. The findings of our study reveal that miR‐210 is down‐regulated in ESCC, which indicates poor prognosis and aggressive tumor progression. Moreover, miR‐210 restoration was found to enhance ESCC viability, invasion, and migration abilities. F‐Box only protein 31 (FBXO31) was confirmed to be one of the targets of miR‐210 in ESCC cells. Results also revealed that miR‐210 played crucial roles in regulating ESCC cell epithelial‐mesenchymal transition (EMT) and Wnt/β‐catenin signaling. In conclusion, data show that miR‐210 serves as an anti‐ESCC miR via down‐regulation of FBXO31 and regulation of EMT and Wnt signaling, suggesting that the miR‐210/FBXO31 axis may function as promising therapeutic targets and effective prognostic markers for ESCC patients.
PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
Authors: Liu Minghui , Cui Liyuan , Li Xin , Xia Chunqiu , Li Yongwen , Wang Rui , Ren Fan , Liu Hongyu , Chen Jun 
Published: February 2021

AbstractBackground: Acquired resistance of chemotherapy, especially cisplatin, is a major challenge in lung cancer treatment. We conducted this study to examine whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse cisplatin resistance in human lung cancer cells. In addition, we explored the underlying mechanisms.Method: We used CCK‐8 assay to got the IC50 of PD‐0332991 and cisplatin in A549 and A549/CDDP respectively. CCK‐8 assay, CalcuSyn 2.0 software, cell cycle distribution and apoptosis used to identify PD‐0332991 could reverse the acquired resistance of cisplatin. At last, western‐blot used to show the mechanism of PD‐0332991 enhances the effects of cisplatin.Results: We found that PD‐0332991 potentiated cisplatin‐induced growth inhibition in both cisplatin‐sensitive (A549) and cisplatin‐resistant (A549/CDDP) cells via downregulation of the proliferation, induction of apoptosis (A549 increased to 7.06%; A549/CDDP increased to 7.03%), and G0/G1 cell cycle arrest (A549 increased to 9.15%; A549/CDDP increased to 49.92%). Western blot analysis revealed that PD‐0332991 enhance the effect of cisplatin through inhibit Rb‐E2Fs pathway.Conclusions: These findings suggest that PD‐0332991 could reverse the acquired resistance of cisplatin in lung cancer cells and provide a novel treatment strategy for lung cancer patients with cisplatin resistance.
Pleural mesothelioma: When echo‐endoscopy (EUS‐B‐FNA) leads to diagnosis in a minimally invasive way
Authors: Piro Roberto , Fontana Matteo , Livrieri Francesco , Menzella Francesco , Casalini Eleonora , Taddei Sofia , De Giorgi Federica , Facciolongo Nicola 
Published: February 2021

AbstractMalignant pleural mesothelioma (MPM) is an asbestos‐related and locally invasive tumor with poor prognosis. The acquisition of histological material is mandatory in order to establish a diagnosis. In this situation, the sampling of tissue is generally performed via a thoracoscopic pleural biopsy, either medically or surgically. The use of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) or transesophageal fine needle aspiration with an EBUS scope (EUS‐B‐FNA) of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report a rare case of MPM successfully diagnosed via EUS‐B‐FNA in a 49‐year‐old woman with an unusual presentation characterized by solid thickening in the right mediastinal pleura.
Long‐term response to afatinib in an elderly patient with uncommon epidermal growth factor receptor mutation‐positive lung adenocarcinoma
Authors: Shijubou Naoki , Sumi Toshiyuki , Kamada Koki , Sawai Takeyuki , Yamada Yuichi , Nakata Hisashi , Mori Yuji , Chiba Hirofumi 
Published: February 2021

AbstractEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are the standard treatment for patients with non‐small cell lung cancer (NSCLC) harboring EGFR mutations. Uncommon mutations, excluding exon 19 deletions and exon 21 L858R, comprise 7%–23% of EGFR mutation‐positive NSCLC. The treatment of uncommon EGFR mutation‐positive NSCLCs is controversial. Here, we present the case of an 81‐year‐old man who was diagnosed with lung adenocarcinoma cStage IVA harboring the uncommon EGFR L861Q mutation. The patient received oral afatinib treatment (40 mg/day). One month after the initiation of afatinib treatment, Common Terminology Criteria for Adverse Events version 4.0 grade 2 stomatitis was observed. It improved upon afatinib withdrawal. After 10 days of withdrawal, afatinib treatment was resumed at a reduced dose of 20 mg/day. Subsequently, the patient continued treatment with afatinib. A partial response to afatinib treatment was maintained for 49 months until primary tumor regrowth. Afatinib treatment was continued after disease progression, but the patient died of bacterial pneumonia 59 months after initiation of afatinib treatment. Several studies have previously reported a large number of compound mutations with uncommon mutations, and that compound mutation‐induced cells are most susceptible to afatinib. This suggests the efficacy of afatinib in clinical practice and that afatinib may be safely administered to elderly patients with appropriate dose reductions.
Telemetry‐validated nitrogen stable isotope clocks identify ocean‐to‐estuarine habitat shifts in mobile organisms
Authors: Shipley Oliver N. , Newton Alisa L. , Frisk Michael G. , Henkes Gregory A. , LaBelle Jake S. , Camhi Merry D. , W. Hyatt Michael , Walters Hans , Olin Jill A. 
Published: February 2021

Abstract

Throughout their life history, many animals transition among heterogeneous environments to facilitate behaviours such as reproduction, foraging and predator avoidance. The dynamic environmental and biological conditions experienced by mobile species are integrated in the chemical composition of their tissues, providing retrospective insight into movement.

Here, we present a unique application of nitrogen stable isotope clocks (‘isotopic clocks’), which integrate tissue turnover rates, consumer stable isotope ratios and habitat‐specific isotope baselines to predict time‐since‐immigration and the timing of habitat shifts in a migratory species. Nitrogen stable isotope values of blood plasma collected from juvenile sand tiger sharks Carcharias taurus, a species known to undertake seasonal movements between ocean and estuarine environments, were used to derive estimates of time‐since‐immigration and the timing of seasonal habitat shifts undertaken by this species.

Nitrogen isotopic clocks estimated for 65 juvenile sand tiger sharks sampled across 6 years indicated that individual sharks predominantly arrived to estuarine habitats between June and July, with some individuals arriving as early as mid‐May. These estimates were validated by comparing isotope‐derived estuarine arrival times with those from acoustically tracked individuals. The median estuarine arrival day estimates from our isotopic approach aligned with estimates from acoustic telemetry for each sampling population.

Sensitivity analyses indicated that isotopically inferred time‐since‐immigration and estuarine arrival estimates were robust to variation in isotopic turnover rate and diet tissue discrimination factors under multiple modelling scenarios. This suggests that parameterization of the nitrogen isotopic clock provides reliable estimates of time‐since‐immigration and day of arrival into new habitats if isotopic variation exists between origin and new locations.

Our study presents a unique application of telemetry‐validated isotope clocks to derive retrospective estimates of time‐since‐immigration and timing of habitat shifts for animals that seasonally traverse heterogeneous environments. This approach can be readily applied across many temporal and spatial scales, and to other species and ecosystems, to facilitate rapid assessment of changes in animal habitat use and broader ecosystem structure.
Inflammatory response, fluid balance and outcome in emergency high‐risk abdominal surgery
Authors: Cihoric Mirjana , Kehlet Henrik , Lauritsen Morten L. , Højlund Jakob , Kanstrup Katrine , Foss Nicolai B. 
Published: February 2021

AbstractBackgroundThe main disease etiologies requiring emergency high‐risk abdominal surgery are intestinal obstruction and perforated viscus and the differences in immune response to these pathologies are largely unexplored. In search of improvement of patient assessment in the perioperative phase, we examined the inflammatory response in this setting, focusing on potential difference in pathophysiology.MethodsThe electronic medical records of 487 patients who underwent emergency abdominal surgery from year 2013‐2015 for intestinal obstruction and perforated viscus were reviewed. We evaluated the relationship between pre‐ and postoperative C‐reactive protein (CRP) trajectory, fluid balance, and perioperative morbidity and mortality according to type of surgery, intervention, and surgical pathology.ResultsA total of 418 patients were included. Pre‐ and postoperative absolute CRP values were significantly higher in patients with perforated viscus (n = 203) than in intestinal obstruction (n = 215) (P < .0001). Relative changes at hour 6 and POD 1 were non‐significant (P = .716 and P = .816 respectively). There was significant association between both pre‐ (quartile 1 vs 4, OR 5.11; P < .01) and postoperative (quartile 1 vs 4, OR 4.10; P < .001) CRP and adverse outcome, along with fluid balance and adverse outcome in patients with obstruction but not in those with perforation. Fluid balance and CRP had statistically significant positive correlation in patients with obstruction.ConclusionsIn this explorative study, a high pre‐ and postoperative CRP and a high positive fluid balance were associated with worse outcome in patients with intestinal obstruction, but not in patients with perforated viscus. Future studies should address the different inflammatory and fluid trajectories in these specific pathologies.
An Experimental Test of the Relationship between Electronic Nicotine Delivery System Use and Alcohol Consumption
Authors: Hershberger Alexandra R. , Studebaker Amanda , Whitt Zachary T. , Fillmore Mark , Kahler Christopher W. , Cyders Melissa A. 
Published: February 2021

BackgroundIncreasing research shows that the use of electronic nicotine delivery systems (ENDS) is associated with a higher rate and quantity of alcohol consumption.MethodsThe present study used a 2‐session, within‐subjects design to experimentally examine the relationship between ENDS use and laboratoryad libitumalcohol consumption. A total ofN = 31 (mean age = 28.71, SD = 11.17; 45.2% women; 54.8% White/Caucasian) healthy adults from the community who use ENDS and endorsed liking beer completed the study, which included a beer consumption taste‐test task that assessed the volume of beer consumed by the participants across 2 counterbalanced sessions: 1 in which concurrent ENDS use was allowed and 1 in which it was not. All analyses controlled for age, race, and gender.ResultsThe effect of ENDS condition on the volume of beer consumed was not statistically significant,F(1, 30) = 0.03,p = 0.86). Results of linear mixed modeling showed that ENDS puffs were significantly related to alcohol sips (estimate = 0.23, SE = 0.07,p = 0.002) across thead libitumsession.ConclusionsOverall, ENDS use did not increase alcohol consumption; however, the data suggest that ENDS puffs might act as a prime for beer sips or that these 2 behaviors are linked through habit. Future studies should more fully measure and compare global and event‐level data on ENDS and alcohol use as they might show disparate patterns of relationships.
Fine‐scale interactions between boats and large albatrosses indicate variable susceptibility to bycatch risk according to species and populations
Authors: Corbeau A. , Collet J. , Orgeret F. , Pistorius P. , Weimerskirch H. 
Published: February 2021

AbstractMany seabirds are attracted to fishing boats where they exploit foraging opportunities, often involving bycatch‐related mortality. Bycatch risk is generally estimated by overlapping seabirds foraging ranges with coarse‐scale monthly maps of fishing efforts, but a more direct estimation would be the time birds actually spend attending fishing boats. Here we matched data from Automatic Identification Systems from all declared boats in the Southern Ocean, with 143 simultaneous foraging trips from all populations of large albatrosses (Diomedea amsterdamensis and Diomedea exulans) breeding in the Indian Ocean (Marion, Crozet, Kerguelen, Amsterdam islands). We quantified and compared real‐time co‐occurrence between boats and albatrosses, at different scales (100, 30 and 5 km). We also examined to what extent co‐occurrence at a large‐scale (5×5° grid cell) predicted fine‐scale attendance (5 km). Albatrosses on average spent about 3 h per trip attending fishing boats (<5 km) at both Amsterdam and Marion and about 30 h per trip at Kerguelen. In all populations, >90% of declared fishing boat attendances occurred within Economic Exclusive Zones (EEZ) where bycatch mitigation measures are enforced. Outside EEZs, birds from all populations to a large extent also attended non‐fishing boats. Fishing boat density at a large scale (5 × 5°, 100 km) was a poor predictor of time spent attending fishing boats (<5 km) across populations. Our results indicate a large variation in fishing boat densities within the foraging ranges of different populations and in the time birds spent attending boats. We discuss the pros and cons of considering bycatch risk at a large geographical scale and methods that can be implemented to improve the estimation of seabird vulnerability to fishing activities when fine‐scale data are available, particularly for the conservation of those highly threatened species.
Epigenetics of alcohol use disorder—A review of recent advances in DNA methylation profiling
Authors: Longley Martha J. , Lee Jisoo , Jung Jeesun , Lohoff Falk W. 
Published: February 2021

AbstractAlcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there is a heritable component, the etiology of AUD is complex and can involve environmental exposures like trauma and can be associated with many different patterns of alcohol consumption. Epigenetic modifications, which can mediate the influence of genetic variants and environmental variables on gene expression, have emerged as an important area of AUD research. Over the past decade, the number of studies investigating AUD and DNA methylation, a form of epigenetic modification, has grown rapidly. Yet we are still far from understanding how DNA methylation contributes to or reflects aspects of AUD. In this paper, we reviewed studies of DNA methylation and AUD and discussed how the field has evolved. We found that global DNA and candidate DNA methylation studies did not produce replicable results. To assess whether findings of epigenome‐wide association studies (EWAS) were replicated, we aggregated significant findings across studies and identified 184 genes and 15 gene ontological pathways that were differentially methylated in at least two studies and four genes and three gene ontological pathways that were differentially methylated in three studies. These genes and pathways repeatedly found enrichment of immune processes, which is in line with recent developments suggesting that the immune system may be altered in AUD. Finally, we assess the current limitations of studies of DNA methylation and AUD and make recommendations on how to design future studies to resolve outstanding questions.
Tyramine synthesis, vesicular packaging, and the SNARE complex function coordinately in astrocytes to regulate Drosophila alcohol sedation
Authors: Lee Kristen M. , Talikoti Ananya , Shelton Keith , Grotewiel Mike 
Published: February 2021

AbstractIdentifying mechanisms underlying alcohol‐related behaviors could provide important insights regarding the etiology of alcohol use disorder. To date, most genetic studies on alcohol‐related behavior in model organisms have focused on neurons, leaving the causal roles of glial mechanisms less comprehensively investigated. Here, we report our studies on the role of Tyrosine decarboxylase 2 (Tdc2), which converts tyrosine to the catecholamine tyramine, in glial cells in Drosophila alcohol sedation. Using genetic approaches that drove transgene expression constitutively in all glia, constitutively in astrocytes and conditionally in glia during adulthood, we found that knockdown and overexpression of Tdc2, respectively, increased and decreased the sensitivity to alcohol sedation in flies. Manipulation of the genes tyramine β‐hydroxylase and tyrosine hydroxylase, which respectively synthesize octopamine and dopamine from tyramine and tyrosine, had no discernable effect on alcohol sedation, suggesting that Tdc2 affects alcohol sedation by regulating tyramine production. We also found that knockdown of the vesicular monoamine transporter (VMAT) and disruption of the SNARE complex in all glia or selectively in astrocytes increased sensitivity to alcohol sedation and that both VMAT and the SNARE complex functioned downstream of Tdc2. Our studies support a model in which the synthesis of tyramine and vesicle‐mediated release of tyramine from adult astrocytes regulates alcohol sedation in Drosophila. Considering that tyramine is functionally orthologous to norepinephrine in mammals, our results raise the possibility that gliotransmitter synthesis release could be a conserved mechanism influencing behavioral responses to alcohol as well as alcohol use disorder.
Honey bees (Hymenoptera: Apidae) outnumber native bees in Tasmanian apple orchards: Perspectives for balancing crop production and native bee conservation
Authors: Prendergast Kit S , Leclercq Nicolas , Vereecken Nicolas J 
Published: February 2021

AbstractApples are a major crop globally, including in Tasmania (Australia) – known as ‘the Apple Isle’ owing to the key role of apples in Tasmania's history and economy. Most apple cultivars are obligate entomophilous species, and fruit quantity, quality and economic value are enhanced under insect pollination. Whilst the introduced European honey bee (Apis mellifera) is often assumed to be the main pollinator of apple in most regions of the world, including Australia, there is an increasing interest in alternative pollinators. The pollinator community of Tasmanian apple crops, however, has never been assessed. In this study, we surveyed four apple orchards for 3 days each during peak bloom in the Huon Valley region to characterise bee assemblages visiting blooming apple trees and the native bee fauna associated with surrounding flowering vegetation. Our results show that honey bees were the predominant visitors to apple blossoms (90.7% of visits), followed by the introduced bumble beeBombus terrestris(5.9% of visits), with only a minor contribution by native bees (3.3% of visits). Twenty‐six species of native bees were collected in total, of which only 10 species (fiveExoneura(Apidae), fourLasioglossum(Halictidae) and oneEuryglossa(Colletidae) species) were collected from apple blossoms, withExoneurabeing the most abundant visitors. Few native bees were captured on apple blossoms, however co‐blooming surrounding native vegetation, as well exotic flowers, hosted a high diversity and abundance of native bees. Site conditions influenced community composition, including abundance and representation of introduced bees compared to native bees visiting apples. Additionally, warmer temperatures favoured native bees. Collectively, our results suggest that Tasmania's apple production in its current state is unlikely to rely exclusively on native pollinators. Native bees nevertheless warrant conservation in such an insular crop production system. This can be achievable through retaining native flowering plants and even exotic non‐crop flowers in and around orchards. Promoting the diversity and abundance of native bees through habitat enhancement may have additional benefits, such as filling current and future pollination demands and gaps, a key strategy under scenarios of climate change.