bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiome meta-analysis and cross-disease comparison enabled by the SIAMCAT machine-learning toolbox
Authors: Wirbel Jakob , Zych Konrad , Essex Morgan , Karcher Nicolai , Kartal Ece , Salazar Guillem , Bork Peer , Sunagawa Shinichi , Zeller Georg
Published: February 2020

The human microbiome is increasingly mined for diagnostic and therapeutic biomarkers using machine learning (ML). However, metagenomics-specific software is scarce and overoptimistic evaluation and limited cross-study generalization are prevailing issues. To address these, we developed SIAMCAT, a versatile R toolbox for ML-based comparative metagenomics. We demonstrate its capabilities in a meta-analysis of fecal metagenomic studies (10,803 samples). When naively transferred across studies, ML models lost accuracy and disease specificity, which could however be resolved by a novel training set augmentation strategy. This revealed some biomarkers to be disease-specific, others shared across multiple conditions. SIAMCAT is freely available from siamcat.embl.de.
Engineering isoprenoid quinone production in yeast
Authors: Kaur Divjot , Corre Christophe , Alberti Fabrizio
Published: February 2020

Isoprenoid quinones are bioactive molecules that include an isoprenoid chain and a quinone head. They are traditionally found to be involved in primary metabolism, where they act as electron transporters, but specialized isoprenoid quinones are also produced by all domains of life. Here, we report the engineering of a baker’s yeast strain,Saccharomyces cerevisiaeEPYFA3, for the production of isoprenoid quinones. Our yeast strain was developed through overexpression of the shikimate pathway in a well-established recipient strain (S. cerevisiaeEPY300) where the mevalonate pathway is overexpressed. As a proof of concept, our new host strain was used to overproduce the endogenous isoprenoid quinone coenzyme Q6, resulting in a final four-fold production increase. EPYFA3 represents a valuable platform for the heterologous production of high value isoprenoid quinones. EPYFA3 will also facilitate the elucidation of isoprenoid quinone biosynthetic pathways.

Abstract Figure
Histopathological aspects of induced resistance byPseudomonas protegensCHA0 and β-aminobutyric acid in wheat againstPuccinia triticina
Authors: Bellameche Fares , Jasim Mohammed A. , Mauch-Mani Brigitte , Mascher Fabio
Published: February 2020

After perception of specific biotic or abiotic stimuli, such as root colonization by rhizobacteria or selected chemicals, plants are able to enhance their basal resistance against pathogens. Due to its sustainability, such induced resistance is highly valuable for disease management in agriculture. Here we study an example of resistance against wheat-leaf rust induced byPseudomonas protegensCHA0 (CHA0) and β-aminobutyric acid (BABA), respectively. Seed dressing with CHA0 reduced the number of sporulating pustules on the leaves and the expression of resistance was visible as necrotic or chlorotic flecks. Moreover, a beneficial effect of CHA0 on growth was observed in wheat seedlings challenged or not with leaf rust. BABA was tested at 10, 15 and 20 mM and a dose-dependent reduction of leaf rust infection was observed with the highest level of protection at 20 mM. However, BABA treatment repressed plant growth at 20 mM. Balancing between BABA-impact on plant growth and its protective capacity, we selected 15 mM as suitable concentration to protect wheat seedlings against leaf rust with the least impact on vegetative growth. To understand the mechanisms behind the observed resistance, we have studied the histological aspects of the fungal infection process. Our results showed that the p re-entry process was not affected by the two resistance inducers. However, both treatments reduced fungal penetration and haustoria formation. The timing and the amplitude of the resistance reactions was different after bacterial or chemical induction, leading to different levels of resistance to leaf rust. During fungal colonization of the tissues, a high deposition of callose and the accumulation of H2O2in both CHA0-and BABA-treated plants pointed to an important contribution to resistance.
A Precision Medicine Approach to Stress Testing Using Metabolomics and Microribonucleic Acids
Authors: Limkakeng Alexander T. , Rowlette Laura-Leigh , Hatch Ace , Nixon Andrew B. , Ilkayeva Olga , Corcoran David L. , Modliszewski Jennifer L. , Griffin S. Michelle , Tsalik Ephraim L. , Ginsburg Geoffrey S. , Voora Deepak
Published: February 2020

Background

Acute coronary syndrome (ACS) is a growing global health problem, and precision medicine techniques hold promise for the development of diagnostic indicators of ACS. In this pilot, we sought to assess the utility of an integrated analysis of metabolomic and microRNA data in peripheral blood to distinguish patients with abnormal cardiac stress testing from matched controls.

Methods

We used prospectively collected samples from emergency department (ED) patients placed in an ED-based observation unit who underwent stress testing for ACS. We isolated microRNA and quantified metabolites from plasma collected before and after stress testing in patients with myocardial ischemia on stress testing versus those with normal stress tests. The combined metabolomic and microRNA data were analyzed jointly for case (ischemia) and 1:1 matched control patients in a supervised, dimension-reducing discriminant analysis. Two integrative models were implemented: a baseline model utilizing data collected prior to stress-testing (T0) and a stress-delta model, which included the difference between post-stress test (T1) and pre-stress test (T0).

Results

Seven case patients with myocardial ischemia on ED cardiac stress testing (6 females, 85% Caucasian, mean Thrombolysis In Myocardial Infarction Score=3, 4 patients ultimately received percutaneous coronary intervention) were 1:1 age and sex-matched to controls. Several metabolites and microRNAs were differentially expressed between cases and controls. Integrative analysis of the baseline levels of metabolites and microRNA expression showed modest performance for distinguishing cases from controls with an overall error rate of 0.143. The stress-delta model showed worse performance for distinguishing cases from controls, with an overall error rate of 0.500.

Conclusions

Given our small sample size, results are hypothesis-generating. However, this pilot study shows a potential method for a precision medicine approach to cardiac stress testing in patients undergoing workup for ACS.
Two antagonistic microtubule targeting drugs act synergistically to kill cancer cells
Authors: Peronne Lauralie , Denarier Eric , Rai Ankit , Prudent Renaud , Vernet Audrey , Suzanne Peggy , Ramirez-Rios Sacnicté , Michallet Sophie , Guidetti Mélanie , Vollaire Julien , Lucena-Agell Daniel , Ribba Anne-Sophie , Josserand Véronique , Coll Jean-Luc , Dallemagne Patrick , Díaz J. Fernando , Oliva María Ángela , Sadoul Karin , Akhmanova Anna , Andrieux Annie , Lafanechère Laurence
Published: February 2020

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for drugs which could potentiate its therapeutic effect. We have screened a chemical library and selected Carba1, a carbazolone, which exerts synergistic cytotoxic effects on tumor cells grownin vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. The Carba1-induced modulation of microtubule dynamics increases the accumulation of fluorescent paclitaxel inside microtubules, providing a mechanistic explanation of the observed synergy between Carba1 and paclitaxel. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observedin vivoin xenografted mice. Thus, a new mechanism favoring paclitaxel accumulation in microtubules can be transposed toin vivomouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.
In situstructure determination of virus capsids imaged within cell nuclei by correlative light and cryo-electron tomography
Authors: Vijayakrishnan Swetha , McElwee Marion , Loney Colin , Rixon Frazer , Bhella David
Published: February 2020

Cryo electron microscopy (cryo-EM), a key method for structure determination involves imaging purified material embedded in vitreous ice. Images are then computationally processed to obtain three-dimensional structures at atomic resolution. There is increasing interest in extending structural studies by cryo-EM into the cell, where biological structures and processes may be imaged in context. The limited penetrating power of electrons prevents imaging of thick specimens (>500 nm) however. Cryo-sectioning methods employed to overcome this are technically challenging, subject to artefacts or involve specialised equipment of limited availability. Here we describe the first structure of herpesvirus capsids determined by sub-tomogram averaging from nuclei of eukaryotic cells, achieved by cryo-electron tomography (cryo-ET) of re-vitrified cell sections prepared using the Tokuyasu method. Our reconstructions reveal that the capsid associated tegument complex is present on capsids prior to nuclear egress. We show that this approach to cryogenic imaging of cells is suited to both correlative light/electron microscopy and 3D structure determination.
FluoSim: simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins
Authors: Lagardère Matthieu , Chamma Ingrid , Bouilhol Emmanuel , Nikolski Macha , Thoumine Olivier
Published: February 2020

Fluorescence live-cell and super-resolution microscopy methods have considerably advanced our understanding of the dynamics and mesoscale organization of macro-molecular complexes that drive cellular functions. However, different imaging techniques can provide quite disparate information about protein motion and organization, owing to their respective experimental ranges and limitations. To address these limitations, we present here a unified computer program that allows one to model and predict membrane protein dynamics at the ensemble and single molecule level, so as to reconcile imaging paradigms and quantitatively characterize protein behavior in complex cellular environments. FluoSim is an interactive real-time simulator of protein dynamics for live-cell imaging methods including SPT, FRAP, PAF, and FCS, and super-resolution imaging techniques such as PALM, dSTORM, and uPAINT. The software, thoroughly validated against experimental data on the canonical neurexin-neuroligin adhesion complex, integrates diffusion coefficients, binding rates, and fluorophore photo-physics to calculate in real time the distribution of thousands of independent molecules in 2D cellular geometries, providing simulated data of protein dynamics and localization directly comparable to actual experiments.
Pro-inflammatory cytokines drive deregulation of potassium channel expression in primary synovial fibroblasts
Authors: Haidar Omar , O’Neill Nathanael , Staunton Caroline A. , Bavan Selvan , O’Brien Fiona , Zouggari Sarah , Sharif Umar , Mobasheri Ali , Kumagai Kosuke , Barrett-Jolley Richard
Published: February 2020

The synovium secretes synovial fluid, but is also richly innervated with nociceptors and acts as a gateway between avascular joint tissues and the circulatory system. Resident fibroblast-like synoviocytes’ (FLS) calcium-activated potassium channels (KCa) change in activity in arthritis models and this correlates with FLSactivation.

Objective

To investigate this activation in anin vitromodel of inflammatory arthritis; 72hr treatment with cytokines TNFα and IL1β.

Methods

FLS cells were isolated from rat synovial membranes. We analysed global changes in FLS mRNA by RNA-sequencing and then focused on FLS ion channels genes and corresponding FLS electrophysiological phenotype, finally modelling data with Ingenuity Pathway Analysis (IPA) and MATLAB.

Results

IPA showed significant activation of inflammatory, osteoarthritic and calcium signalling canonical pathways by cytokines, and we identified ~200 channel gene transcripts. The large KCa(BK) channel consists of the pore forming Kcnma1 together with β-subunits. Following cytokine treatment, a significant increase in Kcnma1 RNA abundance was detected by qPCR and changes in several ion channels were detected by RNA-sequencing, including a loss of BK channel β-subunit expression Kcnmb1/2 and increase in Kcnmb3. In electrophysiological experiments, there was a decrease in overall current density at 20mV without change in chord conductance at this potential.

Conclusion

TNFα and IL1β treatment of FLS in vitro recapitulated several common features of inflammatory arthritis at the transcriptomic level, including increase in Kcnma1 and Kcnmb3 gene expression.
The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse
Authors: Berwian Isabel M. , Wenzel Julia G. , Kuehn Leonie , Schnuerer Inga , Kasper Lars , Veer Ilya M. , Seifritz Erich , Stephan Klaas E. , Walter Henrik , Huys Quentin J. M.
Published: February 2020

The risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.
Type II Fusarium head blight susceptibility factor identified in wheat
Authors: Hales B. , Steed A. , Giovannelli V. , Burt C. , Lemmens M. , Molnár-Láng M. , Nicholson P.
Published: February 2020

Fusarium head blight (FHB) causes significant grain yield and quality reductions in wheat and barley. Most wheat varieties are incapable of preventing FHB spread through the rachis, but disease is typically limited to individually infected spikelets in barley. We point inoculated wheat lines possessing barley chromosome introgressions to test whether FHB resistance could be observed in a wheat genetic background. The most striking differential was between 4H(4D) substitution and 4H addition lines. The 4H addition line was similarly susceptible to the wheat parent, but the 4H(4D) substitution line was highly resistant, which suggests that there is an FHB susceptibility factor on wheat chromosome 4D. Point inoculation of Chinese Spring 4D ditelosomic lines demonstrated that removing 4DS results in high FHB resistance. We genotyped four Chinese Spring 4DS terminal deletion lines to better characterise the deletions in each line. FHB phenotyping indicated that lines del4DS-2 and del4DS-4, containing smaller deletions, were susceptible and had retained the susceptibility factor. Lines del4DS-3 and del4DS-1 contain larger deletions and were both significantly more resistant, and hence had presumably lost the susceptibility factor. Combining the genotyping and phenotyping results allowed us to refine the susceptibility factor to a 31.7 Mbp interval on 4DS.

Highlight

We have identified a Type II Fusarium head blight susceptibility factor on the short arm of wheat chromosome 4D and refined its position to a 31.7 Mbp interval.
Vitamin D regulates MerTK-dependent phagocytosis in human myeloid cells
Authors: Clarke Jelani , Yaqubi Moein , Futhey Naomi C. , Sedaghat Sara , Baufeld Caroline , Blain Manon , Baranzini Sergio , Butovsky Oleg , White John H. , Antel Jack , Healy Luke M.
Published: February 2020

Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis (MS). The major circulating metabolite of vitamin D (25OHD) is converted to the active form (calcitriol) by the hydroxylase enzymeCYP27B1. In MS lesions the tyrosine kinase MerTK expressed by microglia and macrophages regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. We show that calcitriol downregulates MerTK mRNA and protein expression in adult human microglia and monocyte-derived macrophages, thereby inhibiting myelin phagocytosis and apoptotic cell clearance. Proinflammatory myeloid cells express high levels ofCYP27B1compared to homeostatic (TGFβ-treated) myeloid cells. Only proinflammatory cells in the presence of TNF-α generate calcitriol from 25OHD, resulting in repression of MerTK expression and function. The selective production of calcitriol in proinflammatory myeloid cells leading to downregulation of MerTK-mediated phagocytosis has the potential to reduce the risk for auto-antigen presentation while retaining the phagocytic ability of homeostatic myeloid cells, thereby contributing to inflammation reduction and enhanced tissue repair.
TaxisPy: A Python-based Software for the Quantitative Analysis of Bacterial Chemotaxis
Authors: Valderrama-Gómez Miguel Á. , Schomer Rebecca A. , Savageau Michael A. , Parales Rebecca E.
Published: February 2020

Several species of bacteria are able to modify their swimming behavior in response to chemical attractants or repellents. Methods for the quantitative analysis of bacterial chemotaxis such as quantitative capillary assays are tedious and time-consuming. Computer-based video analysis of swimming bacteria represents a valuable method to directly assess their chemotactic response. Even though multiple studies have used this approach to elucidate various aspects of the bacterial chemotaxis, to date, no computer software for such analyses is freely available. Here, we introduce TaxisPy, a Python-based software for the quantitative analysis of bacterial chemotaxis. The software comes with an intuitive graphical user interface and can be easily accessed through Docker on any operating system. Using a video of freely swimming cells as input, TaxisPy estimates the culture’s average tumbling frequency over time. We demonstrate the utility of the software by assessing the effect of different concentrations of the attractant shikimate on the swimming behavior ofPseudomonas putidaF1 and by capturing the adaptation process thatEscherichia coliundergoes after being exposed to L-aspartate.
Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type-1 diabetes
Authors: Kim Heejoo , Perovanovic Jelena , Shakya Arvind , Shen Zuolian , German Cody N. , Ibarra Andrea , Jafek Jillian L. , Lin Nai-Pin , Evavold Brian D. , Chou Danny H.-C. , Jensen Peter E. , He Xiao , Tantin Dean
Published: February 2020

The transcriptional coregulator OCA-B promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. We hypothesized that T cell-specific OCA-B deletion and pharmacologic OCA-B inhibition would protect mice from autoimmune diabetes. We developed anOcabconditional allele and backcrossed it onto a diabetes-prone NOD/ShiLtJ strain background. T cell-specific OCA-B loss protected mice from spontaneous disease. Protection was associated with large reductions in islet CD8+T cell receptor specificities associated with diabetes pathogenesis. CD4+clones associated with diabetes were present, but associated with anergic phenotypes. The protective effect of OCA-B loss was recapitulated using autoantigen-specific NY8.3 mice, but diminished in monoclonal models specific to artificial or neoantigens. Rationally-designed membrane-penetrating OCA-B peptide inhibitors normalized glucose levels, and reduced T cell infiltration and proinflammatory cytokine expression in newly-diabetic NOD mice. Together, the results indicate that OCA-B is a potent autoimmune regulator and a promising target for pharmacologic inhibition.

~40-word summary statement for the online JEM table of contents and alerts

Kim and colleagues show that OCA-B in T cells is essential for the generation of type-1 diabetes. OCA-B loss leaves the pancreatic lymph nodes largely undisturbed, but associates autoreactive CD4+T cells in the pancreas with anergy while deleting potentially autoreactive CD8+T cells.

Kim et al. show that loss or inhibition of OCA-B in T cells protects mice from type-1 diabetes.
Multi-organ transcriptomic landscape ofAmbystoma velascimetamorphosis
Authors: Janet Palacios-Martínez , Juan Caballero-Pérez , Annie Espinal-Centeno , Gilberto Marquez-Chavoya , Hilda Lomelí , Enrique Salas-Vidal , Denhi Schnabel , Jesus Chimal-Monroy , Alfredo Cruz-Ramírez
Published: February 2020

Metamorphosis is a postembryonic developmental process that involves morphophysiological and behavioral changes, allowing organisms to adapt into a novel environment. In some amphibians, aquatic organisms undergo metamorphosis to adapt in a terrestrial environment. These organisms experience major changes in their circulatory, respiratory, digestive, excretory and reproductive systems. We performed a transcriptional global analysis of heart, lung and gills during diverse stages ofAmbystoma velascimetamorphosis. In our analyses, we identified eight gene clusters for each organ, according to the expression patterns of differentially expressed genes. We found 4,064 differentially expressed genes in the heart, 4,107 in the lung and 8,265 in the gills. Among the differentially expressed genes in the heart, we observed genes involved in the differentiation of cardiomyocytes in the interatrial zone, vasculogenesis and in the maturation of coronary vessels. In the lung, we found genes differentially expressed related to angiogenesis, alveolarization and synthesis of the surfactant protein. In the case of the gills, the most prominent biological processes identified are degradation of extracellular matrix, apoptosis and keratin production. Our study sheds light on the transcriptional responses and the pathways involved in the transformation of the facultative metamorphic salamanderA. velasciin an organ-specific manner.
Emerging trends in the literature of value co-creation: a bibliometric analysis
Authors: Saha Victor , Mani Venkatesh , Goyal Praveen
Published: February 2020

Purpose

The purpose of this paper is to review the extant literature on value co-creation using bibliometric analysis in an attempt to gauge the evolving journey of this concept since its inception in the business and management domain.

Design/methodology/approach

Based on a bibliometric analysis of 458 research articles retrieved from the Thompson Reuters’ Web of Science Core Collection™ for the period of 2004–July 2018, this study carries out the following bibliometric techniques: citation analysis, co-citation analysis and co-occurrence of author keywords.

Findings

The study reveals the nature and direction of research that the field of value co-creation has taken over the past decade. Three significant areas emerge out as prominent themes in the literature of value co-creation: value co-creation in the context of customer service, value co-creation in the context of enhancing brand value and value co-creation for marketing of services through the adoption of service logic. Apart from these, the study also reveals the most influential authors, journals, institutions and countries pertaining to the research on value co-creation, along with the possible future directions of research in this area.

Research limitations/implications

This study has limitations in terms of usage of a single database and its inability to contextualize the citation structure of articles revealed from the review.

Practical implications

This study would enable practitioners gain a comprehensive understanding of the concept of value co-creation that they can eventually adopt as a strategy for enhancing their business growth, customer satisfaction and customer loyalty.

Originality/value

This study identifies the intellectual structure of the value co-creation literature and maps out the gradual advancement of the field over the years.
School governing body for parents' productive involvement in South Africa
Authors: Quan-Baffour Kofi Poku
Published: February 2020

Purpose

The democratic constitution that came into effect in 1994 and ushered in the new South Africa recognises parents' role in education hence the established of an innovative school governance structure of which parents are in the majority. Before then, there existed parents–teachers association in schools. Its members were handpicked and therefore undemocratic and ineffective. The purpose of this paper is to investigate how the innovation in school governance encourages parents in the rural areas to be productively involved in school matters.

Design/methodology/approach

The study used the qualitative research method of focus group interviews to explore the extent to which the school governing body fosters active involvement of parents in school matters. The purposive sampling technique was used in selecting 21 school governors from three rural schools who were deemed information-rich to participate in the study.

Findings

The study found that the post-apartheid school governing body concept, which is an innovation in education management and leadership, encourages and promotes productive parents' involvement in education of their children.

Originality/value

The findings have lessons and implications for school management and leadership in the developing countries because as an Africa adage says, “it takes a whole village to bring up a child”.
Formation mechanism of environmental protection behaviours of community residents
Authors: Xu Ruihua , Luo Fan , Chen Xiaofang , Li Mingze , Barua Zapan
Published: February 2020

Purpose

The purpose of this paper is to analyse the characteristics of environmental protection behaviours of community residents from the perspective of system dynamics.

Design/methodology/approach

Documentation method is used to collect the factors and environmental improvement intervention strategies that influence the environmental protection behaviours of community residents from the top journals. To analyse the characteristics of the environmental protection behaviours of community residents which are nonlinear and dynamic, system dynamics (SD) are drawn. The initial value for simulation is obtained from the investigation report of some communities in China by questionnaires method.

Findings

The simulation shows that a process of continuous and interactional feedback is formed among environmental improvement intervention strategies, living context, environmental behavioural intention and environmental protection behaviours. These influences affect how environmental protection behaviour is affected by frequency of community environmental publicity, frequency of community participation regulation and local government investment, all of which are significant and decrease successively. Living context and environmental behavioural intention, which are intervened by the three strategies, can promote community residents’ environmental protection behaviours and reduce the degree of environmental pollution in communities.

Practical implications

The goal of reducing the community environmental pollution may be achieved, because the community environmental management departments can use this system dynamics approach to intervene the environmental protection behaviours of community residents.

Originality/value

The nonlinear and dynamic interactions among influencing factors are illustrated for an in-depth understanding of the environmental protection behaviours of community residents in this study. In addition, the initial parameter value and correlation coefficients are obtained for simulation through the questionnaire survey given to Chinese community residents to avoid the subjectivity of system dynamics.
Local and disease control for nasal melanoma treated with radiation and concomitant anti‐programmed death 1 antibody
Authors: Hanaoka Yuma , Tanemura Atsushi , Takafuji Madoka , Kiyohara Eiji , Arase Noriko , Suzuki Osamu , Isohashi Fumiaki , Ogawa Kazuhiko , Fujimoto Manabu
Published: February 2020

Mucosal melanoma of the nasal cavity is a rare disease that has been consistently associated with poor outcome. While complete surgical excision offers the only prospect of a cure, it is associated with a high risk of surgical morbidity due to the challenging anatomical location, and most patients still develop incurable metastatic disease. The efficacy of immunotherapy on mucosal melanoma is lower in comparison with cutaneous melanoma, and mucosal melanoma rarely has BRAF mutations. Although preclinical data have shown that combination treatment with immune checkpoint inhibitors and radiotherapy (RT) improve the response, there have been few reports on the combination of RT and anti‐programmed death 1 therapy for mucosal melanoma of the nasal cavity. We retrospectively investigated 10 cases of mucosal melanoma of the nasal cavity in which combined treatment was applied. The local control (LC) rate of the primary lesion and regional lymph nodes was favorably 100%. On the other hand, the median progression‐free survival (PFS) time was 29.6 weeks (range, 2–82). The 6‐month PFS rate was 60%. Although severe mucositis occurred in one patient, the incidence of treatment‐related adverse events was not significantly increased. RT with anti‐programmed death 1 antibody therapy for mucosal melanoma of the nasal cavity was tolerable and had the potential to improve LC and PFS.
Structural complexity‐guided predictive filtering
Authors: Liu Bin , Fu Chao , Ren Yuxiao , Zhang Qingsong , Xu Xinji , Chen Yangkang
Published: February 2020

Random noise attenuation utilizing predictive filtering achieves great performance in denoising seismic data. Conventional predictive filtering methods are based on fixed filter operators and neglect the complexity of structures. In this way, the denoised data cannot meet the requirement of balancing the signal preservation and noise removal. In this study, we proposed a structural complexity‐guided predictive filtering method that utilizes an adapted filter operator to adjust the changes of structural complexity. The proposed structural complexity‐guided predictive filtering mainly consists of two stages. A slope field information is acquired according to plane‐wave destruction to assess the structural complexity. In addition, an adaptive filter operator is obtained to denoise the seismic data according to the adaptive factor. Both synthetic data and real seismic profiles are employed to examine the denoising capacity and flexibility of the refined predictive filtering using adaptive lengths. The analysis of the predicted results shows that adaptive predictive filtering is powerful and has the ability to eliminate random noises with negligible distortions.
Flow regimes control the establishment of invasive crayfish and alter their effects on lotic macroinvertebrate communities
Authors: Mathers Kate L. , White James C. , Fornaroli Riccardo , Chadd Richard
Published: February 2020

Invasive non‐native species (INNS) threaten biodiversity and ecosystem functioning globally. However, there remains a pressing need to understand the environmental factors controlling the dispersal, successful establishment and subsequent ecological impacts of INNS for receiving ecosystems. Here, we examine how region‐wide flow regime magnitudes facilitate the successful establishment of an invasive crayfish species (Pacifastacus leniusculus, signal crayfish) in England (UK). We also consider the interactive effects of invasive crayfish with flow regime variations on the structural and functional diversity of macroinvertebrate communities.

Low‐flow magnitudes increased the likelihood of P. leniusculus establishment, with 80% of recorded invasion dates falling in years with flow magnitudes below average (low‐ and low‐moderate flow classes), whilst only 1.6% occurred in high‐flow years.

Temporal trajectories of structural and functional macroinvertebrate responses in invaded rivers demonstrated reduced diversity compared to control rivers. Lower taxonomic and functional richness measures typically coincided with periods of low discharge in invaded rivers and were greatest during regionally high‐flows.

Macroinvertebrate communities displayed significant structural and functional responses to the interaction between invasive crayfish and flow regime variations. Specifically, a number of low‐ and high‐flow indices yielded significant associations, highlighting the role of extreme hydrological events in shaping INNS effects on receiving ecosystems. We also detected greater ecological effects of invasive crayfish under hydrologically stable conditions. Importantly, and for the first time, we observed that invasive crayfish reversed macroinvertebrate community responses to flow regime cues (e.g. discharge fall rate and minimum flows in the preceding 180 days).

Synthesis and applications. Results from this study indicate that low‐flow events facilitate the spread/establishment of invasive crayfish and correspond with greater ecological effects for receiving ecosystems. Given that low‐flow events are predicted to increase in intensity, duration and frequency over the 21st century, our results highlight the potential threat that invasive crayfish may pose under future hydroclimatic changes. Managing river flow regimes effectively (including maintaining higher flow events and flow variability) is likely to be vital in conserving ecological diversity following crayfish invasion.
Recommended Practices for Macerating Human Thyroid Cartilage
Authors: LaGoy Alexis , Evangelou Elizabeth A. , Somogyi Tessa , DiGangi Elizabeth A.
Published: February 2020

Visible abnormalities on the thyroid cartilage may be indicative of perimortem trauma including fractures or sharp force trauma. During autopsy, the thyroid cartilage must be freed of surrounding soft tissue before these abnormalities can be clearly observed. Several processing methods were first experimentally tested on pig ears to narrow down which might work best to process human thyroid cartilage. Several methods in the categories of hot water maceration, chemical/enzyme maceration, and dermestid beetles were then tested on a sample of 37 human thyroid cartilages. An adapted 22‐point scoring system was used to score the efficacy of each processing method. Chemical maceration using bleach was found to be the best method for removing surrounding tissue from thyroid cartilage, with Arm & HammerTM powdered laundry detergent as a close second. These methods are inexpensive, quick, and easy to implement, making them a simple addition to busy medical examiner’s offices or forensic anthropology laboratories.
Cannabis use and stressful life events during the perinatal period: cross‐sectional results from Pregnancy Risk Assessment Monitoring System (PRAMS) data, 2016
Authors: Allen Alicia M. , Jung Alesia M. , Alexander Adam C. , Allen Sharon S. , Ward Kenneth D. , al'Absi Mustafa
Published: February 2020

Aims

We aimed to determine the association between stressful life events (SLEs) in the year prior to childbirth with (1) pre‐pregnancy cannabis use, (2) cessation of cannabis use during pregnancy and (3) postpartum relapse to cannabis use.

Design

We used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) 2016, a cross‐sectional, population‐based surveillance system.

Setting

Mailed and telephone surveys conducted in five states—Alaska, Colorado, Maine, Michigan and Washington—in the United States.

Participants

Women (n = 6061) who delivered a live infant within the last 6 months and had data on cannabis use.

Measurements

Self‐reported data included SLEs (yes/no response for 14 individual events in the 12 months prior to childbirth) and cannabis use [yes/no prior to pregnancy, during pregnancy, and at the time of the survey (approximately 2–6 months postpartum)]. The associations between SLEs and cannabis use (primary outcomes) were examined in logistic regression models adjusted for maternal demographics (e.g. age, race, education), geography (i.e. state of residence) and cigarette smoking.

Findings

Pre‐pregnancy, 16.4% (997/6061) of respondents endorsed using cannabis, with 36.4% (363/997) continuing cannabis use during pregnancy. Among the 63.6% (634/997) who did not report use during pregnancy, 23.2% (147/634) relapsed to cannabis use during the postpartum. Nine of the 14 possible SLEs were associated with increased odds of pre‐pregnancy cannabis use [e.g. husband/partner or mother went to jail, adjusted odds ratio (aOR) = 2.16, 95% confidence interval (CI) = 1.30–3.62] and four were associated with increased odds of continued cannabis use during pregnancy (e.g. husband/partner lost job, aOR = 2.19, 95% CI = 1.21–3.96). The odds of postpartum relapse to cannabis were significantly associated with two SLEs (husband/partner said they did not want pregnancy, aOR = 2.86, CI = 1.10–7.72; husband/partner or mother went to jail, aOR = 0.37, 95% CI = 0.13–1.00).

Conclusions

Stressful life events during the year prior to childbirth appear to be linked to greater odds of women's cannabis use during the perinatal period, especially during pre‐pregnancy.
The potential of the estimands framework for clinical pharmacology trials: Some discussion points
Authors: Ring Arne , Wolfsegger Martin J.
Published: February 2020

The recently finalised and published guideline ICH E9 (R1) introduced a new framework for the statistical analysis of clinical trials, namely that of “estimands”. While the framework was originally developed for the analysis of late‐phase trials, it could also provide a rigorous basis for the analysis of clinical pharmacology trials. We illustrate potential applications on two examples: a multiple dose pharmacology trial and the interpretation of confirmatory bioequivalence (BE) trials according to the current FDA and EMA BE guidelines.
Regulation of iron homeostasis through the erythroferrone‐hepcidin axis in sickle cell disease
Authors: Mangaonkar Abhishek A. , Thawer Fahim , Son James , Ajebo Germame , Xu Hongyan , Barrett Nadine J. , Wells Leigh G. , Bowman Latanya , Clair Betsy , Patel Niren , Bora Pritam , Jung Grace , Nemeth Elizabeta , Kutlar Abdullah
Published: February 2020

Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion‐dependent β‐thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non‐IO cases, n = 11), and non‐SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non‐SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non‐IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non‐IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = −0·2, P = 0·4). Although a direct non‐linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0·4, P = 0·08) and non‐IO state (Spearman ρ = −0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.
Impact of lymphoma‐linked Asn11Tyr point mutation on the interaction between Bcl‐2 and a BH3 mimetic: Insights from molecular dynamics simulation
Authors: Singh Khushboo , Briggs James M.
Published: February 2020

Frequent mutations in the Bcl‐2 anti‐apoptotic protein are often implicated in diffuse large B‐cell lymphoma (DLBCL), a disease profoundly resistant to drugs. Bcl‐2‐competitive inhibitors, “BH3 mimetics,” activate apoptosis by interfering with the interactions between pro‐apoptotic BH3 domains and the hydrophobic groove of Bcl‐2. The aim of our research is to determine the potential of DLBCL‐linked N11Y mutation to facilitate resistance against a “BH3 mimetic” using molecular dynamics simulation. Binding free energy calculations suggest a significant decrease in the binding affinity in the mutant model. In‐depth analysis of the models using residue interaction network, dynamic cross‐correlation, and free energy landscape approaches reveal that the mutation modifies the conformations of key residues, thereby altering the shape of the hydrophobic groove. This subsequently changes the ligand orientation and counteracts the phenomenon of LB region unwinding, a crucial event observed in the wild‐type model. Lowest frequency motions captured by principal component analysis reflect the stretching of the groove for efficient ligand accommodation in the wild‐type complex but not in the mutant model. This is the first in silico study that unravels the mechanism of drug resistance induced by a Bcl‐2 mutation, which could be of great relevance while designing and tailoring therapeutics.
Slavery and Anglo‐American capitalism revisited
Authors: Wright Gavin
Published: February 2020

British and American debates on the relationship between slavery and economic growth have had little interaction with each other. This article attempts intellectual arbitrage by joining these two literatures. The linkage turns on the neglected part two of the ‘Williams thesis’: that slavery and the slave trade, once vital for the expansion of British industry and commerce, were no longer needed by the nineteenth century. In contrast to recent assertions of the centrality of slavery for US economic development, the article argues that part two of the Williams thesis applies with equal force to nineteenth‐century America. Unlike sugar, cotton required no large investments of fixed capital and could be cultivated efficiently at any scale, in locations that would have been settled by free farmers in the absence of slavery. Cheap cotton was undoubtedly important for the growth of textiles, but cheap cotton did not require slavery. The best evidence for this claim is that after two decades of war, abolition, and Reconstruction, cotton prices returned to their prewar levels. In both countries, the rise of anti‐slavery sentiment was not driven by the prospect of direct economic benefits, but major economic interest groups acquiesced in abolition because they no longer saw slavery as indispensable.
Sustainability at a cost: An inceptive analysis of “extended” fishing ban on the livelihoods of fishers of Tamil Nadu
Authors: Amali Infantina John , Priya Parasuram , Deepak Samuel Vijay Kumar , Abhilash Kottarathil Rajendiran , Purvaja Ramchandran , Ramesh Ramachandran
Published: February 2020

An emphasis on sustainable marine fish production has paved the way for the enactment of Marine Fisheries Regulation Acts and subsequent regulations in India. A closed season ban on fishing has been one of the very few successful regulatory measures since its introduction in 2001 in Tamil Nadu. Since 2017, the fishing ban period has been extended from 45 to 60 days for the east coast of India, for ecosystem‐based marine fisheries management. This study analyses the socioeconomic impacts of change in the fishing ban (closed season) across the four coastal zones of Tamil Nadu. For the past 10 years, CPUE has been stable or increased marginally. Among the four coasts, the relative change in employment and labour income loss was highest for Palk Bay (36.84%). Transaction costs of implementation of the ban caused an additional expense of Rs 496.5 million to the Government in 2017 and the overall total labour income loss has leaped from Rs 1,638.2 to 2,100.2 million due to the extension of the ban. The fishing ban has aided in the recovery of habitat and regeneration of stock through recruitment. Training and capacity building on alternative livelihood options are highly recommended to enable the workers to cope with the ban period.
Lung inflammation in the pathogenesis of rheumatoid arthritis
Authors: Demoruelle M. Kristen , Wilson Timothy M. , Deane Kevin D.
Published: February 2020

The primary manifestation of rheumatoid arthritis (RA) is articular disease; however, extra‐articular disease can also occur. In particular, pulmonary disease is a leading cause of morbidity and mortality in individuals with RA. Herein, we will review the types, prevalence, risk factors, and potential pathophysiology of lung disease in individuals with established RA. We will also discuss the emerging understanding of potential role of the lung in the generation of RA‐related autoantibodies during a period of disease development termed “pre‐RA.” Finally, we will discuss a research agenda outlining the next steps to improve our understanding and management of lung inflammation and lung disease throughout the natural history of RA.