bluuebunny/crossref_metadata_2025 huggingface dataset:
Resolving spatial complexities of hybridization in the context of the gray zone of speciation in North American ratsnakes (Pantherophis obsoletuscomplex)
Authors: Burbrink Frank T. , Gehara Marcelo , Myers Edward A.
Published: May 2020

Inferring the history of divergence between species in a framework that permits the presence of gene flow has been crucial for characterizing the gray zone of speciation, which is the period of time where lineages have diverged but have not yet achieved strict reproductive isolation. However, estimates of both divergence times and rates gene flow often ignore spatial information, for example the formation and shape of hybrid zones. Using population genomic data from the eastern ratsnake complex (Pantherophis obsoletus), we infer phylogeographic groups, gene flow, changes in demography, the timing of divergence, and hybrid zone widths. We examine the spatial context of diversification by linking migration and timing of divergence to the location and widths of hybrid zones. Artificial neural network approaches are applied to understand how landscape features and past climate have influenced population genetic structure among these lineages prior to hybridization. Rates of migration between lineages are associated with the width and shape of hybrid zones. Timing of divergence is not related to migration rate across species pairs and is therefore a poor proxy for inferring position in the gray zone. However, timing of divergence is related to the number of loci weakly introgressing through hybrid zones.
Adapt or perish: Evolutionary rescue in a gradually deteriorating environment
Authors: Marrec Loïc , Bitbol Anne-Florence
Published: May 2020

We investigate the evolutionary rescue of a microbial population in a gradually deteriorating environment, through a combination of analytical calculations and stochastic simulations. We consider a population destined for extinction in the absence of mutants, which can only survive if mutants sufficiently adapted to the new environment arise and fix. We show that mutants that appear later during the environment deterioration have a higher probability to fix. The rescue probability of the population increases with a sigmoidal shape when the product of the carrying capacity and of the mutation probability increases. Furthermore, we find that rescue becomes more likely for smaller population sizes and/or mutation probabilities if the environment degradation is slower, which illustrates the key impact of the rapidity of environment degradation on the fate of a population. We also show that our main conclusions are robust across various types of adaptive mutants, including specialist and generalist ones, as well as mutants modeling antimicrobial resistance evolution. We further express the average time of appearance of the mutants that do rescue the population and the average extinction time of those that do not. Our methods can be applied to other situations with continuously variable fitnesses and population sizes, and our analytical predictions are valid in the weak-to-moderate mutation regime.
Dispersal alters the nature and scope of sexually antagonistic variation
Authors: Flintham Ewan O , Savolainen Vincent , Mullon Charles
Published: May 2020

Intralocus sexual conflict, or sexual antagonism, occurs when alleles have opposing fitness effects in the two sexes. Previous theory suggests that sexual antagonism is a driver of genetic variation by generating balancing selection. However, most of these studies assume that populations are well-mixed, neglecting the effects of spatial subdivision. Here we use mathematical modelling to show that limited dispersal changes evolution at sexually antagonistic autosomal and X-linked loci due to inbreeding and sex-specific kin competition. We find that if the sexes disperse at different rates, kin competition within the philopatric sex biases intralocus conflict in favour of the more dispersive sex. Furthermore, kin competition diminishes the strength of balancing selection relative to genetic drift, reducing genetic variation in small subdivided populations. Meanwhile, by decreasing heterozygosity, inbreeding reduces the scope for sexually antagonistic polymorphism due to nonadditive allelic effects, and this occurs to a greater extent on the X-chromosome than autosomes. Overall, our results indicate that spatial structure is a relevant factor in predicting where sexually antagonistic alleles might be observed. We suggest that sex-specific dispersal ecology and demography can contribute to interspecific and intragenomic variation in sexual antagonism.
Promoter activity-based case-control association study onSLC6A4highlighting hypermethylation and altered amygdala volume in male patients with schizophrenia
Authors: Ikegame Tempei , Bundo Miki , Okada Naohiro , Murata Yui , Koike Shinsuke , Sugawara Hiroko , Saito Takeo , Ikeda Masashi , Owada Keiho , Fukunaga Masaki , Yamashita Fumio , Koshiyama Daisuke , Natsubori Tatsunobu , Iwashiro Norichika , Asai Tatsuro , Yoshikawa Akane , Nishimura Fumichika , Kawamura Yoshiya , Ishigooka Jun , Kakiuchi Chihiro , Sasaki Tsukasa , Abe Osamu , Hashimoto Ryota , Iwata Nakao , Yamasue Hidenori , Kato Tadafumi , Kasai Kiyoto , Iwamoto Kazuya
Published: May 2020

Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding geneSLC6A4and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations ofSLC6A4in schizophrenia (SZ). We examined CpG sites ofSLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using three independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site inSLC6A4in male patients with SZ in all three cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and thatin vitroDNA methylation at this CpG site diminished the promoter activity ofSLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site inSLC6A4is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.
The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2
Authors: Di Gioacchino Andrea , Šulc Petr , Komarova Anastassia V. , Greenbaum Benjamin D. , Monasson Rémi , Cocco Simona
Published: May 2020

COVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We find that the CpG content, which we characterize by a force parameter that accounts for statistical constraints acting on the genome at the nucleotidic and amino-acid levels, is, on average, low compared to other pathogenic betacoronaviruses. However, the CpG force widely fluctuates along the genome, with a particularly low value, comparable to the circulating seasonal HKU1, in the spike coding region and a greater value, comparable to SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3’UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the Zinc finger Anti-viral Protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition-transversion bias and the pressure to lower CpG content.
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

The 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

Intense 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 statement

This 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

Whereas 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

Despite 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

Background

People 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.

Objective

The 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).

Methods

Following 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.

Results

We 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).

Conclusions

These 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.
Systemic immune dysfunction in cancer patients driven by IL6 and IL8 induction of an inhibitory receptor module in peripheral CD8+T cells
Authors: Somasundaram Ashwin , Cillo Anthony R. , Lampenfeld Caleb , Oliveri Lauren , Velez Maria A. , Joyce Sonali , Calderon Michael J. , Dadey Rebekah , Rajasundaram Dhivyaa , Normolle Daniel P. , Watkins Simon C. , Herman James G. , Kirkwood John M. , Lipson Evan J. , Ferris Robert L. , Bruno Tullia C. , Vignali Dario A.A.
Published: May 2020

Many cancer patients do not develop a durable response to the current standard of care immunotherapies despite substantial advances in targeting immune inhibitory receptors1-5. A potential compounding issue, which may serve as an unappreciated, dominant resistance mechanism, is an inherent systemic immune dysfunction that is often associated with advanced cancer6-12. Minimal response to inhibitory receptor (IR) blockade therapy and increased disease burden have been associated with peripheral CD8+T cell dysfunction, characterized by suboptimal T cell proliferation and chronic expression of IRs (eg. Programmed Death 1 [PD1] and Lymphocyte Activation Gene 3 [LAG3])13, 14. Here, we demonstrate that up to a third of cancer patients express robust intracellular LAG3 (LAG3IC), but not surface LAG3 (LAG3SUR), in peripheral CD8+T cells compared to CD4+T cells and regulatory T cells (Tregs). LAG3ICis associated with: (i) expression of a LAG3IC-dominant IR module that includes PD1IC, NRP1IC, CD39IC, and TIGITIC; (ii) decreased CD8+but not CD4+T cell function that can be reversed by anti-LAG3 (and/or anti-PD1), despite limited constitutive surface IR expression; and (iii) poor disease prognosis. Systemic immune dysfunction is restricted to CD8+T cells, including a high percentage of peripheral naïve CD8+T cells, indicating a TCR-independent mechanism that is driven by the cytokine IL6 and the chemokine IL8. Thus, the combination of an increased LAG3-dominant IR module and elevated systemic IL6 and/or IL8 may serve as predictive biomarkers and increase the possibility that cancer patients will benefit from therapeutic combinations targeting these systemic cytokines in the setting of PD1 and/or LAG3 blockade.
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

Peroxisomes 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

Bacteria 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.

Importance

For 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

Coronavirus 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

Purpose

On 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/approach

Across three-wave data collected from 220 hotel frontline employees, this study tests the proposed model using structural equation modeling through AMOS.

Findings

Employees’ perceived organizational error tolerance positively influenced their psychological well-being through significant sequential mediation effects of POS and OBSE.

Practical implications

This 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/value

This 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

Purpose

This 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/approach

As 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.

Findings

The 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/implications

This 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 implications

This 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/value

This 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

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

Objective

Attention 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.

Design

National register‐based cohort study.

Setting

Sweden.

Population

Nulliparous women giving birth to singleton infants 2007–2014 (n = 377 381).

Methods

Women 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 measures

Preterm birth (<37 weeks).

Results

During 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.

Conclusions

Women with ADHD (i.e. who had been dispensed ADHD medication at any time in 2005–2014) had an increased risk of preterm birth.

Tweetable abstract

Women 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

Background

Insufficient data exist for peristomal pyoderma gangrenosum (PPG), which primarily affects patients with inflammatory bowel disease (IBD).

Aims

To evaluate the risk factors and treatment response of PPG in IBD patients in a real‐life cohort.

Methods

Cases 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.

Results

The 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%).

Conclusions

Female 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

Despite 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.
Possible mechanisms of cancer prevention by nicotinamide
Authors: Buqué Aitziber , Bloy Norma , Kroemer Guido , Galluzzi Lorenzo
Published: May 2020

Nicotinamide (NAM) is a precursor of vitamin B3 commonly sold over the counter as a nutritional supplement with anti‐aging properties. Accumulating preclinical evidence indicates that NAM also mediates oncopreventive effects against a variety of neoplasms. Supporting the translational relevance of dietary NAM supplementation, results from a Phase 3 randomized clinical trial have demonstrated that oral NAM was safe and efficiently reduced the incidence of new non‐melanoma skin cancers and actinic keratosis amongst high‐risk individuals. However, the molecular and cellular mechanisms that underlie this ability of NAM to delay carcinogenesis remain to be clarified, as discussed in this short review.

LINKED ARTICLES

This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
The role of the microbiome in the neurobiology of social behaviour
Authors: Sarkar Amar , Harty Siobhán , Johnson Katerina V.‐A. , Moeller Andrew H. , Carmody Rachel N. , Lehto Soili M. , Erdman Susan E. , Dunbar Robin I. M. , Burnet Philip W. J.
Published: May 2020

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the ‘social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of ‘social’ signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome‐associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe–depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome–sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.
Citizen and government co‐production of data: Analyzing the challenges to government adoption of VGI
Authors: Khan Zarin T. , Johnson Peter A.
Published: May 2020

With the recent rise of open government and open data initiatives, governments are increasingly adopting new approaches of citizen participation to support a more democratic, transparent, and inclusive government system. Among other forms of citizen participation, Volunteered Geographic Information (VGI) is one approach to connecting citizens and government. Accepting VGI as a way to update government data or collect near‐real‐time information from citizens can create a partner‐like relationship where citizens voluntarily contribute time and effort to support government actions. However, as a relatively new approach to citizen participation and data collection, VGI requires evaluation from the perspective of governments. This research investigates the challenges and opportunities that governments have found through the implementation of VGI projects. Results are drawn from interviews conducted with 19 government organizations, revealing organizational and technical challenges that limit the adoption of VGI. Organizational challenges are associated with government mindset, implementation, and project management, while technical challenges involve development of the system and quality of data. Given these challenges, we derive recommendations within the phases of project initiation, implementation, and expansion that can foster VGI adoption in government.
Managing innovation performance: Results from an industry‐spanning explorative study on R&D key measures
Authors: Bican Peter M. , Brem Alexander
Published: May 2020

Research on R&D performance measures applied in firms is still scarce. Based on the established “R&D laboratory as a system” thinking, systematically derive and identify R&D department level key performance measures. Through a mixed‐method approach, grounded in (1) literature and (2) text analysis, 154 R&D performance measures were developed. Amongst those, an (3) online expert survey, as well as (4) three independent focus group workshops with >40 industry experts from more than ten industries identified and validated ten key R&D performance measures. All industry experts involved are members of an innovation network, additionally accounting for innovation network effects. In contrast to earlier research, some of the measures like degree of anticipation of internal customer needs were perceived both by the survey respondents and the focus groups as key measures, indicating that behavioral measures should not be excluded per se. However, the importance of external validity of R&D performance or indicators to measure performance in relation to activities outside the R&D department were not confirmed. Hence, we partly confirm the relevance of the original “R&D Lab” measures, contributing a more granular level, thereby drawing implications for future research and practice.
Global application of oral disease prevention and health promotion as measured 10 years after the 2007 World Health Assembly statement on oral health
Authors: Petersen Poul Erik , Baez Ramon J , Ogawa Hiroshi
Published: May 2020

Objectives

The WHO World Health Assembly established in 2007 a Resolution (WHA60.17) on oral health, which called upon countries to ensure that public health actions for disease prevention and health promotion are established. The objective of the present survey undertaken 10 years later (2017‐2018) was to measure the application of such programmes for key population age groups in low‐, middle‐ and high‐income countries.

Methods

Oral health focal points of ministries of health worldwide (n = 101) answered a structured questionnaire on existing national oral health systems and the actual public health activities. The response rate was 58.4%. The questionnaire was used to collect information about structural factors, country workforce, financial models, provision of preventive services and promotion for oral health, school health programmes, administration of fluoride, national oral health targets and oral health surveillance. The countries were classified by national income for analysis of data.

Results

Coverage of population groups by primary oral health care and emergency care varied by national income. The gap between countries in delivery of preventive care was strong since low‐income countries less often reported preventive activities than middle‐income countries and particularly when compared to high‐income countries. School oral health programmes were less frequent in low‐income than other countries. Moreover, population methods of fluoridation and use of fluoridated toothpaste were unusual in low‐income countries. Health education, mass communication and community events were often essential elements in health promotion. In disease prevention, many countries considered the link between oral health and general health conditions and intervention towards shared risk factors of NCDs. The health concern for the consumption of tobacco, unhealthy diet and sugars was particularly emphasized by high‐income countries but less highlighted by low‐income countries. Finally, while national oral health targets for children and surveillance systems were frequently reported by countries, similar systems for adolescents, adults and older people were rare.

Conclusions

The inequities between countries in oral disease prevention and health promotion were substantial. Limited financial resources for preventive care and health promotion; inadequate workforce for oral health, and insufficient coverage in primary health care were observed in low‐resource countries. The results of the survey demonstrate the need for building effective oral health systems oriented towards oral disease prevention and health promotion.
Expertise Shapes Multimodal Imagery for Wine
Authors: Croijmans Ilja , Speed Laura J. , Arshamian Artin , Majid Asifa
Published: May 2020

Although taste and smell seem hard to imagine, some people nevertheless report vivid imagery in these sensory modalities. We investigate whether experts are better able to imagine smells and tastes because they have learned the ability, or whether they are better imaginers in the first place, and so become experts. To test this, we first compared a group of wine experts to yoked novices using a battery of questionnaires. We show for the first time that experts report greater vividness of wine imagery, with no difference in vividness across sensory modalities. In contrast, novices had more vivid color imagery than taste or odor imagery for wines. Experts and novices did not differ on other vividness of imagery measures, suggesting a domain‐specific effect of expertise. Critically, in a second study, we followed a group of students commencing a wine course and a group of matched control participants. Students and controls did not differ before the course, but after the wine course students reported more vivid wine imagery. We provide evidence that expertise improves imagery, exemplifying the extent of plasticity of cognition underlying the chemical senses.
The Interaction Effect of Goal Misalignment and Metaknowledge Distribution on Team Decision Making in Operations and Supply Chain Management
Authors: Franke Henrik , Foerstl Kai , Heese H. Sebastian
Published: May 2020

Many strategic decisions concerning firms’ operations and supply chain management (OSCM) are executed in teams of multiple functional specialists, to reap the proven benefits of internal integration. However, specialists bring with them not only diverse expertise, but also diverse goals and incentive structures. We examine how functional goal misalignment and the distribution of knowledge of who knows what (metaknowledge) affect self‐serving politics and the performance of cross‐functional teams. To test our model, we develop a vignette‐based social team experiment and analyze data from 468 participants grouped in 156 sourcing teams. Our results provide evidence for both catalyst and inverse‐catalyst effects of the distribution of metaknowledge. Specifically, under goal alignment, centralized metaknowledge leads to the catalyzation of cross‐functional expertise, reducing team politics and enhancing team performance. However, under goal misalignment, centralized metaknowledge significantly amplifies team politics and reduces performance via mediation. We contribute to the growing body of research on behavioral OSCM at the team level of analysis by offering theoretical and practical implications for the design of team integration processes from the perspective of organizational politics and group cognition. We also provide management with clear design recommendations regarding how to govern cross‐functional OSCM teams in terms of functional goals and the distribution of metaknowledge.