bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A
Authors: Reisenauer Keighley N. , Tao Yongfeng , Song Shuxuan , Patel Saawan D. , Ingros Alec , Sheesley Peter , Masi Marco , Boari Angela , Evidente Antonio , Kornienko Alexander V. , Romo Daniel , Taube Joseph 
Published: May 2020

AbstractThe epithelial-mesenchymal transition (EMT) imparts properties of cancer stem-like cells, including resistance to frequently used chemotherapy, necessitating the identification of molecules that induce cell death specifically in stem-like cells with EMT properties. Herein, we demonstrate that breast cancer cells enriched for EMT features are more sensitive to cytotoxicity induced by ophiobolin A (OpA), a sesterterpenoid natural product. Using a model of experimentally induced EMT in human mammary epithelial (HMLE) cells, we show that EMT is both necessary and sufficient for OpA sensitivity. Moreover, prolonged, sub-cytotoxic exposure to OpA is sufficient to reduce migration, sphere formation, and resistance to doxorubicin. OpA is well-tolerated in mice and treatment with OpA alone reduces tumor burden. These data identify a driver of EMT-driven cytotoxicity with significant potential for use either in combination with standard chemotherapy or for tumors enriched for EMT features.
Baffling: A cheater strategy using self-made tools in tree crickets
Authors: Deb Rittik , Modak Sambita , Balakrishnan Rohini 
Published: May 2020

AbstractIntense sexual selection in the form of mate choice can facilitate the evolution of different alternative reproductive strategies. These strategies can be condition-dependent, wherein genetically similar individuals express the strategy based on their condition. Our study shows that baffling, a mate attraction strategy using self-made acoustic amplifiers, employed by male tree crickets, is a classic example of a condition-dependent alternative strategy. We show that less preferred males, who are smaller or produce less loud calls, predominantly use this alternative strategy. Baffling allows these males to increase their call loudness and advertisement range, and attract a higher number of mates. Baffling also allows these males to deceive females into mating for longer durations with them. Our results suggest that the advantage of baffling in terms of sperm transfer is primarily limited to less preferred males, thus maintaining the polymorphism of calling strategies in the population.Impact statementThis study shows that less preferred tree cricket males use an alternative signaling strategy to call louder, thus attracting and mating with otherwise choosy females using deception.
A Method to sort heterogenous cell populations based on migration in 2D and 3D environments
Authors: Arora Aditya , Niño Jorge Luis Galeano , Myaing Myint Zu , Arasi Bakya , Huang Ruby Yun-Ju , Dasgupta Ramanuj , Biro Maté , Viasnoff Virgile 
Published: May 2020

ABSTRACTWhereas phenotypic assays such as Boyden chambers and wound healing assays can easily be employed to characterize the migratory potential of cells at the population level, few methods exist that can sort subpopulations of cells based on their migratory behaviour from an initial heterogeneous pool. In this paper, we present an approach to sort migratory cancer and immune cells based on their spontaneous migration in 2D and 3D microenvironments. Using this method, which is easy to implement and readily scalable, millions of live cells can be sorted based on their migratory characteristics and then subjected to downstream genomic, molecular and functional tests. We reveal that enrichment of the most migratory cytotoxic T lymphocytes yields a pool of cells with enhanced cytotoxicity against cancer cells. This new functional sorting method opens new avenues for the precise characterization of the mechanisms underlying hitherto unexplained heterogeneities in migratory phenotypes within a cell population, and for the targeted enrichment of the most potent migratory leukocytes in immunotherapies.
Mind the gap: preventing circularity in missense variant prediction
Authors: Heijl Stephan , Vroling Bas , van den Bergh Tom , Joosten Henk-Jan 
Published: May 2020

AbstractDespite advances in the field of missense variant effect prediction, the real clinical utility of current computational approaches remains rather limited. There is a large difference in performance metrics reported by developers and those observed in the real world. Most currently available predictors suffer from one or more types of circularity in their training and evaluation strategies that lead to overestimation of predictive performance. We present a generic strategy that is independent of dataset properties and algorithms used, to deal with circularity in the training phase. This results in more robust predictors and evaluation scores that accurately reflect the real-world performance of predictive models. Additionally, we show that commonly used training methods can have an adverse impact on model performance and lead to gross overestimation of true predictive performance.
Effects of targeted assistance and perturbations on the relationship between pelvis motion and step width in people with chronic stroke
Authors: Reimold Nicholas K. , Knapp Holly A. , Chesnutt Alyssa N. , Agne Alexa , Dean Jesse C. 
Published: May 2020

AbstractBackgroundPeople with chronic stroke (PwCS) often exhibit a weakened relationship between pelvis motion and paretic step width, a behavior important for gait stabilization. We have developed a force-field able to manipulate this relationship on a step-by-step basis.ObjectiveThe objective of this study was to investigate the effects of a single exposure to our novel force-field on the step-by-step modulation of paretic step width among PwCS, quantified by the partial correlation between mediolateral pelvis displacement at the start of a step and paretic step width (step start paretic ρdisp).MethodsFollowing a 3-minute period of normal walking, participants were exposed to 5-minutes of either force-field assistance (n=10; pushing the swing leg toward a mechanically-appropriate step width) or perturbations (n=10; pushing the swing leg away from a mechanically-appropriate step width). This period of assistance or perturbations was followed by a 1-minute catch period to identify any after-effects, a sign of sensorimotor adaptation.ResultsWe found that assistance did not have a significant direct effect or after-effect on step start paretic ρdisp. In contrast, perturbations directly reduced step start paretic ρdisp(p=0.004), but were followed by an after-effect in which this metric was increased above the baseline level (p=0.02).ConclusionsThese initial results suggest that PwCS have the ability to strengthen the link between pelvis motion and paretic foot placement if exposed to a novel mechanical environment, which may benefit gait stability. Future work is needed to determine whether this effect can be extended with repeated exposure to force-field perturbations.
Fusarium verticillioidesFvPex8 is a key component of peroxisomal docking/translocation module that serves important roles in fumonisin biosynthesis but not in virulence
Authors: Yu Wenying , Lin Mei , Peng Minghui , Yan Huijuan , Zhou Jie , Lu Guodong , Shim Won Bo , Wang Zonghua 
Published: May 2020

AbstractPeroxisomes are ubiquitous organelles in eukaryotic cells that fulfill various important metabolic functions. In this study, we investigated the role of Docking/Translocation Module (DTM) peroxins, mainly FvPex8, FvPex13, FvPex14, and FvPex33, inFusarium verticillioidesvirulence and fumonisin B1 (FB1) biosynthesis. Protein interaction experiments suggested that FvPex13 serves as the core subunit ofF. verticillioidesDTM. When we generated gene deletion mutants (ΔFvpex8, ΔFvpex13, ΔFvpex14, ΔFvpex33, ΔFvpex33/14) and examined whether the expression of other peroxin genes were affected in the DTM mutants, ΔFvpex8 strain showed most drastic changes toPEXgene expression profiles. Deletion mutants exhibited disparity in carbon source utilization and defect in cell wall integrity when stress agents were applied. Under nutrient starvation, mutants also showed higher levels of lipid droplet accumulation. Notably, ΔFvpex8 mutant showed significant FB1 reduction and altered expression ofFUM1andFUM19genes. However, FvPex13 was primarily responsible for virulence, while ΔFvpex33/14 double mutant also showed virulence defect. In summary, our study suggests that FvPex13 is the core component of DTM, regulating peroxisome membrane biogenesis as well as PTS1- and PTS2-mediated transmembrane cargo transportation. Importantly, we predict FvPex8 as a key component in DTM that affects peroxisome function in FB1 biosynthesis inF. verticillioides.
Bacterial evolution in high osmolarity environments
Authors: Cesar Spencer , Anjur-Dietrich Maya , Yu Brian , Li Ethan , Rojas Enrique , Neff Norma , Cooper Tim F. , Huang Kerwyn Casey 
Published: May 2020

AbstractBacteria must maintain a cytosolic osmolarity higher than that of their environment in order to take up water. High osmolarity environments therefore present a formidable stress to bacteria. To explore the evolutionary mechanisms by which bacteria adapt to high osmolarity environments, we selectedEscherichia coliin media with a variety of osmolytes and concentrations for 250 generations. Adaptation was osmolyte-dependent, with sorbitol stress generally resulting in increased fitness in conditions with higher osmolarity, while selection in high concentrations of proline resulted in increased fitness specifically on proline. Consistent with these phenotypes, sequencing of the evolved populations showed that passaging in proline resulted in specific mutations in an associated metabolic pathway that increases the ability to utilize proline for growth, while evolution in sorbitol resulted in mutations in many different genes that generally improve growth in high osmolarity conditions at the expense of growth at low osmolarity. High osmolarity decreased growth rate but increased mean cell volume compared with growth on proline as the sole carbon source, demonstrating that osmolarity-induced changes in growth rate and cell size follow an orthogonal relationship from the classical Growth Law relating cell size and nutrient quality. Isolates from a sorbitol-evolved population that capture the likely temporal sequence of mutations revealed by metagenomic sequencing demonstrate a tradeoff between growth at high and low osmolarity. Our study highlights the utility of experimental evolution for dissecting complex cellular networks and environmental interactions, particularly in the case of behaviors that can involve both specific and general metabolic stressors.ImportanceFor bacteria, maintaining higher internal solute concentrations than the environment allows cells to take up water. As a result, survival is challenging in high osmolarity environments. To investigate how bacteria adapt to high osmolarity environments, we evolvedEscherichia coliin a variety of high osmolarity solutions for hundreds of generations. We found that evolved populations adopted different strategies to improve their growth depending on the osmotic passaging condition, either generally adapting to high osmolarity conditions or better metabolizing the osmolyte as carbon source. Single-cell imaging demonstrated that enhanced fitness was coupled to faster growth, and metagenomic sequencing revealed mutations that reflect growth tradeoffs across osmolarities. Our study demonstrates the utility of long-term evolution experiments for probing adaptation during environmental stress.
A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs
Authors: Rocca María Florencia , Zintgraff Jonathan Cristian , Dattero María Elena , Santos Leonardo Silva , Ledesma Martín , Vay Carlos , Prieto Mónica , Benedetti Estefanía , Avaro Martín , Russo Mara , Nachtigall Fabiane Manke , Baumeister Elsa 
Published: May 2020

AbstractCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid, sensitive and specific diagnosis of SARS-CoV-2 by fast and unambiguous testing is widely recognized to be critical in responding to the ongoing outbreak. Since the current testing capacity of RT-PCR-based methods is being challenged due to the extraordinary demand of supplies, such as RNA extraction kits and PCR reagents worldwide, alternative and/or complementary testing assays should be developed. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied.
Why should errors be tolerated? Perceived organizational support, organization-based self-esteem and psychological well-being
Authors: Wang Xingyu , Guchait Priyanko , Paşamehmetoğlu Aysin 
Published: May 2020

PurposeOn the basis of conservation of resources theory, the purpose of this paper is to propose a framework linking an organizational factor, organizational error tolerance, with employees’ psychological well-being through gains of psychological resources: perceived organizational support (POS) and organization-based self-esteem (OBSE).Design/methodology/approachAcross three-wave data collected from 220 hotel frontline employees, this study tests the proposed model using structural equation modeling through AMOS.FindingsEmployees’ perceived organizational error tolerance positively influenced their psychological well-being through significant sequential mediation effects of POS and OBSE.Practical implicationsThis study contributes to the existing literature of psychological resources, positive psychology and error management by providing insights into how organizational practice in error situations can be positively related to employees’ psychological well-being.Originality/valueThis paper identifies error-related organizational practices as precursor of individual psychological well-being and explores the non-work-related outcome variable of error management for the first time. The examination of the linkage between organizational error tolerance and employees’ psychological well-being via the underlying mechanism of psychological resources provides the insight into how resources dynamics play important roles in influencing employees’ psychological well-being.
Impact of attitude towards a region on purchase intention of regional products: the mediating effects of perceived value and preference
Authors: Charton-Vachet Florence , Lombart Cindy , Louis Didier 
Published: May 2020

PurposeThis research has three research objectives. First, this research will demonstrate that the link between consumers' attitude towards a region and their intention to purchase products from that region is not direct but indirect. Second, this research will establish that perceived value of regional products and consumers' preference for these products are mediating variables of the relationship between consumers' attitude towards a region and their intention to purchase regional products. Lastly, this research will highlight cognitive (through perceived value) and affective (through preference) routes or paths, from consumers' attitude towards a region to their purchase intention of products from that region.Design/methodology/approachAs previous works in the authors’ field of research, the authors conducted a field study, combined with a questionnaire survey. 398 consumers responded to the authors’ questionnaire in a hypermarket (belonging to the retailer Système U) in Vendée (a region in France). The authors measured their attitude towards this region, their preference for regional food products and their purchase intention of these products as well as the perceived value of regional food products.FindingsThe perceived value of regional products and consumers' preference for these products are full mediating variables of the relationship between consumers' attitude towards a region and their intention to purchase products from that region.Research limitations/implicationsThis research supplements prior works. It shows that the link between consumers' attitude towards a region and their intention to purchase regional products is indirect. Consumers' purchase intention of regional products is not directly attributable to their attitude towards the region of origin of these products. Regional products and their features have to be reintegrated into this equation.Practical implicationsThis study identifies several routes or paths to explain consumers' purchase intention of regional products. A cognitive route or path, from consumers' attitude towards a region to their purchase intention of products from that region, mediates by perceived value. An affective route or path, from consumers' attitude towards a region to their purchase intention of products from that region, mediates by preference. A hybrid path that combines cognitive and affective paths, as this research established a link between perceived value and preference.Originality/valueThis research foregrounds regional products and their features, too often neglected in favour of consumers and their characteristics.
Private Schools and Queue-jumping: A reply to White
Authors: Kidd Ian James , Jago Mark 
Published: May 2020

Abstract
John White defends the UK private school system from the accusation that it allows an unfair form of ‘queue jumping’ in university admissions. He offers two responses to this accusation, one based on considerations of harm, and one based on meritocratic distribution of university places. We will argue that neither response succeeds: the queue-jumping argument remains a powerful case against the private school system in the UK. We begin by briefly outlining the queue-jumping argument, before evaluating White's no-harm and meritocracy arguments.
Association of maternal attention deficit hyperactivity disorder and preterm birth: a cohort study
Authors: Hesselman S , Wikman A , Skoglund C , Kopp Kallner H , Skalkidou A , Sundström‐Poromaa I , Wikström A‐K 
Published: May 2020

ObjectiveAttention deficit hyperactivity disorder (ADHD) affects 3–7% of women of childbearing age. Whether ADHD is associated with an increased risk of preterm birth is unclear.DesignNational register‐based cohort study.SettingSweden.PopulationNulliparous women giving birth to singleton infants 2007–2014 (n = 377 381).MethodsWomen were considered to have ADHD if they had been dispensed at least one prescription for ADHD medication, i.e. a central nervous system stimulant or non‐stimulant drugs for ADHD, prior to, during or after pregnancy (2005–2014). Women with ADHD were compared with women without ADHD in regard to prevalence, severity and mode of onset of preterm birth. Logistic regression models were used, estimating adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age and country of birth (model 1), and in addition for body mass index (BMI), education, alcohol or substance use disorders, and pre‐gestational medical and psychiatric co‐morbidity (model 2).Main outcome measuresPreterm birth (<37 weeks).ResultsDuring the study period, 6327 (1.7%) women gave birth and had ADHD according to our definition. These women had a higher rate of preterm birth compared with women without ADHD (7.3 versus 5.8%, aOR model 2: 1.17; 95% CI 1.05–1.30). ADHD was particularly associated with very (<32 weeks) preterm births, and associations were seen with both spontaneous and medically indicated onsets.ConclusionsWomen with ADHD (i.e. who had been dispensed ADHD medication at any time in 2005–2014) had an increased risk of preterm birth.Tweetable abstractWomen with ADHD have a higher risk of preterm birth but most of it is due to modifiable risk factors.
Risk factors and treatment outcomes of peristomal pyoderma gangrenosum in patients with inflammatory bowel disease
Authors: Wang Jingzhou , Prenner Joshua , Wang Wenfei , Sakuraba Atsushi , Hyman Neil , Dalal Sushila , Hurst Roger , Cohen Russell D. , Umanskiy Konstantin , Shogan Benjamin D. , Alpert Lindsay , Rubin David T. , Colwell Janice , Pekow Joel 
Published: May 2020

SummaryBackgroundInsufficient data exist for peristomal pyoderma gangrenosum (PPG), which primarily affects patients with inflammatory bowel disease (IBD).AimsTo evaluate the risk factors and treatment response of PPG in IBD patients in a real‐life cohort.MethodsCases of PPG were identified retrospectively using ICD‐9/10 codes in patients with IBD who had an ostomy at a tertiary care centre. Disease‐specific characteristics were compared between groups with and without PPG, and response to therapy was evaluated in patients with PPG.ResultsThe cohort included 41 IBD patients with PPG and 123 IBD controls with an ostomy who never developed PPG. Patients with PPG were more likely to be female (76% vs 51%, P = 0.006), had higher BMIs (29.78 ± 0.89 vs 23.53 ± 0.51, P < 0.0001) and had increased usage of pouch belts (97% vs 71%, P = 0.0008) compared to controls. There were no differences in age at surgery (41.76 ± 2.60 vs 43.49 ± 1.50, P = 0.57) or IBD diagnosis (63% vs 54% Crohn's disease, P = 0.28) between PPG and controls. 85% of PPG patients achieved complete resolution with different treatments, including surgery. Complete resolution with topical corticosteroids and calcineurin inhibitors alone were low (14% and 13% respectively). Higher rates of complete resolution were reported with anti‐tumour necrosis factor (TNF) agents (63%) and surgical interventions (80%).ConclusionsFemale gender, higher BMI and pouch belts were associated with increased risk of developing PPG. Most PPG cases resolved after treatment with the highest rates of complete resolution seen with anti‐TNF agents and surgical intervention.
Tumour‐immune microenvironment in duodenal‐type follicular lymphoma
Authors: Inoue Hiroaki , Rai Shinya , Tanaka Hirokazu , Espinoza J. Luis , Watatani Yosaku , Kumode Takahiro , Serizawa Kentaro , Nakayama Shoko , Taniguchi Yasuhiro , Morita Yasuyoshi , Tatsumi Yoichi , Ashida Takashi , Matsumura Itaru 
Published: May 2020

SummaryDespite duodenal‐type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited‐stage FL (LSFL; n = 19) and advanced‐stage FL (ASFL; n = 31). The mean number of CD8+ tumour‐infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm2) than in LSFL (1,150/mm2) and ASFL (1,188/mm2) (P = 0·002, P = 0·002, respectively). In addition, CD8+PD1− T cells with non‐exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer‐lasting T cell‐mediated immune response. Moreover, whereas FOXP3+CTLA‐4+ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm2), they were more abundant in LSFL (78/mm2) and ASFL (109/mm2) (P = 2·80 × 10−5, P = 4·74 × 10−8, respectively), and the numbers of eTregs correlated inversely with those of CD8+ TILs (r = −0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3hiCD45RA‐CD25hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10−7, respectively). These results suggest that the augmented anti‐tumour immune reactions may contribute to a better prognosis on DTFL.