bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking long-term functional connectivity maps in human stem-cell-derived neuronal networks by holographic-optogenetic stimulation
Authors: Schmieder Felix , Habibey Rouhollah , Striebel Johannes , Büttner Lars , Czarske Jürgen , Busskamp Volker
Published: May 2021

Neuronal networks derived from human induced pluripotent stem cells (hiPSCs) have been exploited widely for modelling neuronal circuits, neurological diseases and drug screening. As these networks require extended culturing periods to functionally maturein vitro, most studies are based on immature networks. To obtain insights on long-term functional features of human networks, we improved a long-term glia-co-culture culturing protocol directly on multi-electrode arrays (MEA), facilitating long-term assessment of electrical features at weekly intervals. We applied optogenetic stimulation to induce neuronal activity, which resulted in accelerated neuronal responses during network development. Using holographic stimulation with single-cell-resolution, propagating evoked activities of 400 individually stimulated neurons per MEA were traceable, and precise network functional connectivity motifs were revealed. Our integrated holographic optogenetic stimulation platform on MEAs facilitates studying long-term functional dynamics of human neuronal networksin vitro. This is an important step towards establishing hiPSC-derived neurons as profound functional testbeds for basic and biomedical research.

Highlights

Integrated platform allowed long-term optogenetic experiments on hiPSC-derived networks.

Full-field optogenetic stimulation boosted hiPSC-derived neuronal network activity.

Single-neuron resolution holographic stimulation evoked local responses in the network.

Holographic stimulation of each neuron revealed its functional connectivity patterns.

Subsequent holographic stimulation of more than 400 neurons revealed the whole network connectivity map.
Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions
Authors: Zhang Yuning , Ho Tiffany D. , Buchler Nicolas E. , Gordân Raluca
Published: May 2021

Most eukaryotic transcription factors (TFs) are part of large protein families, with members of the same family (i.e., paralogous TFs) recognizing similar DNA-binding motifs but performing different regulatory functions. Many TF paralogs are coexpressed in the cell and thus can compete for target sites across the genome. However, this competition is rarely taken into account when studying the in vivo binding patterns of eukaryotic TFs. Here, we show that direct competition for DNA binding between TF paralogs is a major determinant of their genomic binding patterns. Using yeast proteins Cbf1 and Pho4 as our model system, we designed a high-throughput quantitative assay to capture the genomic binding profiles of competing TFs in a cell-free system. Our data show that Cbf1 and Pho4 greatly influence each other's occupancy by competing for their common putative genomic binding sites. The competition is different at different genomic sites, as dictated by the TFs’ expression levels and their divergence in DNA-binding specificity and affinity. Analyses of ChIP-seq data show that the biophysical rules that dictate the competitive TF binding patterns in vitro are also followed in vivo, in the complex cellular environment. Furthermore, the Cbf1-Pho4 competition for genomic sites, as characterized in vitro using our new assay, plays a critical role in the specific activation of their target genes in the cell. Overall, our study highlights the importance of direct TF-TF competition for genomic binding and gene regulation by TF paralogs, and proposes an approach for studying this competition in a quantitative and high-throughput manner.
Personal income tax design and background-related earnings advantages: evidence from Italy and Poland
Authors: Bloise Francesco , Franzini Maurizio , Raitano Michele
Published: May 2021

Purpose

The authors analyse how the association between parental background and adult children's earnings changes when net rather than gross children's earnings are considered and disentangle what such changes depend on: differences between pre and after taxes earnings inequality or reranking of individuals along the earnings distribution before and after taxes.

Design/methodology/approach

Using data from European Union Statistics on Income and Living Conditions (EU-SILC) 2011, the authors focus on two large European countries, Italy and Poland, with comparable levels of inequality and background-related earnings premia but very different personal income tax (PIT) design and estimate – at both the mean and the deciles of the earnings distribution – the association between parents' characteristics and children's gross and net earnings.

Findings

The authors find that in Italy the PIT reduces the magnitude of the association between parental background and adult children's earnings at the top of the distribution, while no effects emerge for Poland, and the reduction is mostly due to a decrease in earnings inequality rather than to a re-ranking of children along the distribution. The findings are confirmed when the authors simulate the introduction of a “quasi flat tax” regime in Italy.

Social implications

The findings suggest that the higher the tax progressivity, the higher the background-related inequality reduction and the lower the intergenerational association, signalling that the degree of progressivity amongst children may be an effective weapon to reduce intergenerational inequality.

Originality/value

In the literature on intergenerational inequality, the role of taxes is usually overlooked. In this paper, the authors try to fill this gap and enquire how the PIT design affects the association between parental background and adult children's earnings.
Evaluation of enablers of cloud technology to boost industry 4.0 adoption in the manufacturing micro, small and medium enterprises
Authors: Subramanian Geetha , Patil Bhushan T. , Gardas Bhaskar B.
Published: May 2021

Purpose

Cloud technology is extremely critical for the continuing progress of Industry 4.0 and it helps in pooling centralized information for the business. Further, it offers a platform for collaboration for improving the performance of the industry. This paper aims to investigate the factors affecting the implementation of cloud technology for boosting Industry 4.0 adoption in micro, small and medium enterprises (MSMEs) of the manufacturing sector.

Design/methodology/approach

A total of 14 enablers were considered for the case study which were obtained from the literature survey and shortlisted by the experts of the domain (academia and industries). The interpretive structural modelling (ISM) approach has been used as a methodology for exploring the relationships between the enablers. Matrices impact croises multiplication applique and classment (MICMAC) analysis has been carried out for the validation of the developed structural model. MICMAC analysis helps to identify driving power and dependency potential of all considered enablers.

Findings

The results of the investigation indicate that three factors, namely, system integration, project management and competitive pressure, were significant. These factors drive all other considered factors in the implementation process.

Research limitations/implications

The opinions of the experts from the industry and academia were analyzed for the development of the hierarchical model and these inputs could be biased. This investigation intends to help the decision makers in the effective adoption of the cloud and Industry 4.0 technologies and for the formulation of the efficient implementation policies.

Originality/value

The present study aims to focus on cloud technology as well as Industry 4.0 in the context of manufacturing MSMEs and none of the previous investigations analyzed the enablers that influence the adoption of cloud technology for boosting Industry 4.0, especially using the ISM approach.
Sharing economy services in Dhaka: a change towards women’s perception of commuting
Authors: Hoque Md. Mukitul , Saumi Bildana Haque
Published: May 2021

Purpose

In the modern era of transportation, using a ride-sharing service can add an extra value to the lifestyles of women. Also, women are thinking about the ride-sharing service, what are the factors they consider while purchasing the service and so on. The purpose of this study is to find out women’s perception of ride-sharing services.

Design/methodology/approach

This paper is based on deductive research approach and descriptive research design. This paper has followed mixed research method by using qualitative and quantitative data. By dividing the larger population into subgroups, the researchers have conducted a survey on 240 respondents. To select these respondents, researchers have applied simple random technique. Based on a survey on consumers’ buying behaviour of ride-sharing service, the researchers tested the impact of tangibility, reliability, safety, fare, efficiency and convenience as the factors for choosing ride-share rather than other public transportation.

Findings

The study results indicate that reliability which includes consistency, punctuality and schedule routes are the major concerning issue for women while choosing ride-share service. Women are also concerned about efficiency which includes global positioning system tracking, smartphone technology and so on. One of the important criteria for choosing a ride-sharing service is safety, which includes verified drivers, and drivers review scores. So, reliability, efficiency and safety are the most effective issues. On the other hand, tangibility, fare and convenience do not affect that much.

Originality/value

To the best of the authors’ knowledge, this is the first research to scrutinize the sharing economy service in Dhaka city towards women’s perception of commuting.
Roads pose a significant barrier to bee movement, mediated by road size, traffic and bee identity
Authors: Fitch Gordon , Vaidya Chatura
Published: May 2021

Roads are a major driver of environmental stress, yet we know surprisingly little about how roads impact the movement of insect pollinators, and consequent pollination.

We investigated the influence of roads on pollinator movement and pollination by examining patterns of pigment transfer between focal plants of two species, Coreopsis verticillata and Monarda fistulosa. We asked whether roads reduced pigment transfer, and what characteristics of roads were important in driving this reduction. We also evaluated whether pollinator assemblage differed between species, and if this mediated the effect of roads on pigment transfer.

Plants across a road from a pigment‐added plant received significantly less pigment than plants on the same side of the road. This effect was stronger for coreopsis than for monarda. The mean body size of visitors to coreopsis was significantly smaller than that of visitors to monarda, suggesting that smaller bees are more limited by roads.

Road width was the best predictor of pigment transfer, with a smaller effect of traffic volume; further research is needed to fully disentangle the effects of different road characteristics. Roadside habitat had little influence on pigment transfer, and roadside plants did not receive significantly less pigment than plants in contiguous habitat.

Synthesis and applications. This study demonstrates that roads pose substantial barriers to bee movement, reducing pollen flow between plants located across roadways from one another. Road characteristics, particularly width and traffic volume, mediated this effect, as did bee size. Our results suggest that the effects of roads on pollinators and pollination can be mitigated by many of the same design strategies currently being implemented to reduce human traffic accidents, offering the opportunity for win–win scenarios.
Nucleoid‐associated Rok differentially affects chromosomal transformation on Bacillus subtilis recombination‐deficient cells
Authors: Serrano Ester , Torres Rubén , Alonso Juan C.
Published: May 2021

Rok, a Bacillus subtilis nucleoid‐associated protein (NAP), negatively regulates competence development and silences xenogeneic genes. We show that rok inactivation increases rpoB482 natural intraspecies chromosomal transformation (CT) and plasmid transformation to a different extent. In ΔaddAB, ΔrecO, recF15, ΔrecU, ΔruvAB or rec+ cells intraspecies CT significantly increases, but the ΔrecD2 mutation reduces, and the ΔrecX, ΔradA or ΔdprA mutation further decreases CT in the Δrok context when compared to rok+ cells. These observations support the idea that rok inactivation, by altering the topology of the recipient DNA, differentially affects the integration of homologous DNA in rec‐deficient strains, and in minor extent the competent subpopulation size. The impairment of other NAP (Hbsu or LrpC) also increased intra‐ and interspecies CT (nonself‐DNA, ~8% nucleotide sequence divergence) in rec+ cells, but differentially reduced both types of CTs in certain rec‐deficient strains. We describe that rok inactivation significantly stimulates intra and interspecies CT but differentially reduces them in transformation‐deficient cells, perhaps by altering the nucleoid architecture. We extend the observation to other NAPs (Hbsu, LrpC).
RNase1 can modulate gut microbiota and metabolome after Aeromonas hydrophila infection in blunt snout bream
Authors: Geng Ruijing , Liu Han , Tan Kianann , Wang Zhiqiang , Wang Weimin
Published: May 2021

Pancreatic ribonuclease (RNase1) of Megalobrama amblycephala exhibits both antimicrobial and digestive activity. The gut microbiome improve the digestion and metabolic capacity and enhance the functioning of the immune system of the host against pathogenic bacteria. In this study, we aimed to assess the protective effect of RNase1 on Aeromonas hydrophila‐induced inflammation and intestinal microbial metabolism. Megalobrama amblycephala were randomly divided into three groups: control (injected PBS), infection (A. hydrophila‐injected), and treatment group (RNase1 pretreatment 24 h before the A. hydrophila injection). The morphological symptoms were significantly alleviated by RNase1. RNase1 reshaped the perturbed gut microbiota by upregulating Proteobacteria and Vibrio richness and downregulating Firmicutes, Chlamydiae, Bacillus, and Gemmobacter richness. The lysophosphatidylcholine, (±) 17 HETE, D‐ (+) ‐cellobiose, and PC (20:5) in the treatment group were restored by RNase 1 protein treatment to the level of the control group. In the treatment group, phospholipid metabolism, fatty acid metabolism, glucose metabolism and lipid metabolism were different from the control and infection groups. The proinflammatory factors concentration in intestinal samples significantly increased after A. hydrophila infection. Our results revealed that RNase1 plays an important role in resistance to pathogen invasion, reducing inflammation, and improving intestinal function, thus inhibiting the occurrence of disease.
Tonogenesis in Northeastern Trans‐Himalayan
Authors: Sims Nathaniel A.
Published: May 2021

Tonogenesis is a topic of perennial interest in Trans‐Himalayan linguistics (the name of the family is the subject of some debate. Other terms for the family are Sino‐Tibetan and Tibeto‐Burman). The phonetic origins of the tones of the many languages in the family, such as Tibetan (Huáng 1995), Burmese (Nishi 1999; Hill 2019), and Chinese (Haudricourt 1954; Sagart 1999) are relatively well understood. However, the phonetic origins of tone in many Trans‐Himalayan languages remains an open question (Sagart 2006). There has been a paucity of work describing the origins of tone in the languages classified as belonging to the Qiangic subgroup of Trans‐Himalayan. This paper gives an account of tonogenesis in three tonal subgroups of Trans‐Himalayan languages: Rma (also called 羌 Qiāng (see Wang 1999 for a history of the terminology)) and Prinmi (also called 普米 Pǔmı̌), two modern subgroups, along with Tangut, a mediaeval Trans‐Himalayan language attested from 1042–1502 ce.
Australia’s Forgotten Copper Mining Boom: Understanding How South Australia Avoided Dutch Disease, 1843–1850
Authors: Harris Edwyna , La Croix Sumner
Published: May 2021

Great Britain established the new colony of South Australia (SA) in 1834, and migration from Britain to the colony began in 1836. After seven turbulent years, the discovery of two large deposits of copper at Kapunda (1843–4) and Burra (1844–5) renewed the colony’s economic prospects. Over the 1845–50 period, SA supplied roughly 9 per cent of the world’s copper production. Immigration to SA from Britain soared, with the colony’s population more than tripling between 1844 and 1851. We use the Beine–Coulombe–Vermeulen model of an economy with a booming resource sector to frame our empirical investigation of the boom’s effects on the export of other traded goods and worker living standards. Using newly developed SA wage and price series for this period, we find that immigration mitigated and offset some Dutch disease effects: there were just modest increases in SA living standards, increases in the export of wool and wheat, and a larger share in production for non‐traded goods. Finally, we conclude that the decision by Governor Grey to force broad ownership of the ‘monster’ Burra mine and the use of revenues from land sales to subsidise immigration helped SA avoid the corruption and rent‐seeking associated with other resource booms.
Equity should know no borders: The role of Australasian radiation oncologists in supporting radiation oncology services in low‐ and middle‐income countries in the Asia‐Pacific
Authors: Hassan Sean , Oar Andrew , Ward Iain , Koh Eng‐Siew , Shakespeare Thomas P , Yap Mei Ling
Published: May 2021

The rapid rise in cancer incidence within the world’s poorest nations highlights the need for equitable access to evidence‐based cancer care. It has been previously demonstrated that radiotherapy is a cost‐effective and necessary tool in cancer treatment. However, globally there is a growing divide between demand and supply of radiotherapy services. In low‐ and middle‐income countries, this resource gap is particularly problematic. By region, the Asia‐Pacific has been demonstrated to have the highest absolute deficit in radiotherapy services. Radiation oncologists in Australia and New Zealand are geographically well positioned to assist departments within the Asia‐Pacific to help to reduce these inequities. The Asia‐Pacific Radiation Oncology Special Interest Group (APROSIG) aims to support oncology professionals in the Asia‐Pacific to develop safe and sustainable cancer services. Members have already contributed to multiple projects throughout the region, supported by grants and departmental funding. However, the backbone of support comes from volunteers sharing their time and expertise. The Australasian oncological community has the skills and knowledge to help not only those within our borders but also beyond. Such efforts provide the potential to develop valuable clinical, educational, research and leadership experiences whilst establishing networking opportunities throughout the most populated regions of the world. More options for growth and work in global health must be investigated, encouraging future trainees to consider a role within the global cancer community. Without prompt and continued action, the resource deficit is likely to grow and the inequity in accessing radiotherapy and other cancer services further magnified.
A prospective evaluation of treatment recommendations compared to outcomes for a lung cancer multidisciplinary team and legal implications
Authors: Klemm Daniel , Lehman Margot
Published: May 2021

Introduction

This cross‐sectional study compared treatment recommendations made by a respiratory multi‐disciplinary team with the treatment received by those patients in practice. The aim was to evaluate the rate at which patients were treated in keeping with MDT recommendations. It was hypothesised that most patients would be treated in accordance with these recommendations. These data were then used to provide a practical basis to consider the potential legal liability of multi‐disciplinary teams.

Methods

All patients discussed in the Princess Alexandra Hospital Lung MDT over a three‐month period were included. The recommendations made by the MDT were compared with the treatment received. Where available, the reason for any change in management plan was recorded.

Results

74/109 evaluable patients were treated in accordance with the MDT recommendation. A further 7 patients had commenced treatment prior to MDT discussion. The most common reasons for change in management were patient choice (n = 6) or deterioration in clinical condition prior to treatment (n = 6).

Conclusion

As hypothesised, there was a high rate of treatment in accordance with recommendations made by the MDT. Changes in management are mostly related to patient preference or change in condition after MDT discussion. In practice, there are only limited opportunities for an MDT to be liable for patient outcomes. It is suggested however that careful documentation and representation of cases where appropriate could further mitigate this risk.
Phylogeographic model selection using convolutional neural networks
Authors: Fonseca Emanuel M. , Colli Guarino R. , Werneck Fernanda P. , Carstens Bryan C.
Published: May 2021

The discipline of phylogeography has evolved rapidly in terms of the analytical toolkit used to analyse large genomic data sets. Despite substantial advances, analytical tools that could potentially address the challenges posed by increased model complexity have not been fully explored. For example, deep learning techniques are underutilized for phylogeographic model selection. In non‐model organisms, the lack of information about their ecology and evolution can lead to uncertainty about which demographic models are appropriate. Here, we assess the utility of convolutional neural networks (CNNs) for assessing demographic models in South American lizards in the genus Norops. Three demographic scenarios (constant, expansion, and bottleneck) were considered for each of four inferred population‐level lineages, and we found that the overall model accuracy was higher than 98% for all lineages. We then evaluated a set of 26 models that accounted for evolutionary relationships, gene flow, and changes in effective population size among the four lineages, identifying a single model with an estimated overall accuracy of 87% when using CNNs. The inferred demography of the lizard system suggests that gene flow between non‐sister populations and changes in effective population sizes through time, probably in response to Pleistocene climatic oscillations, have shaped genetic diversity in this system. Approximate Bayesian computation (ABC) was applied to provide a comparison to the performance of CNNs. ABC was unable to identify a single model among the larger set of 26 models in the subsequent analysis. Our results demonstrate that CNNs can be easily and usefully incorporated into the phylogeographer's toolkit.
Interaction Effect of Capital Controls and Macroeconomic Policies
Authors: Zehri Chokri
Published: May 2021

This study highlights recent approaches to reducing capital flow volatility using capital controls. Through a SVAR model, variance decomposition and shocks analysis, applied to 22 developed and developing countries over the period between 2000 and 2017, this study examines the effectiveness of capital controls in reducing capital flow volatility. The results show that the portfolio balance approach of capital controls can be applied and enables to predict capital inflow movements. The findings show asymmetric impacts of capital controls, where a floating exchange rate allows capital controls to be more effective compared to a fixed exchange rate. Furthermore, controls on capital inflows are more useful than controls on outflows. This study found that the exchange rate policy is more responsive to capital controls actions compared to the monetary policy.
Using a risk model for probability of cancer in pulmonary nodules
Authors: Liu Si‐Qi , Ma Xiao‐Bin , Song Wan‐Mei , Li Yi‐Fan , Li Ning , Wang Li‐Na , Liu Jin‐Yue , Tao Ning‐Ning , Li Shi‐Jin , Xu Ting‐Ting , Zhang Qian‐Yun , An Qi‐Qi , Liang Bin , Li Huai‐Chen
Published: May 2021

Background

Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide.

Methods

A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video‐assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm.

Results

The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient.

Conclusions

Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population.
Genomic signatures of demographic declines in an imperiled amphibian inform conservation action
Authors: Hardy B. M. , Pope K. L. , Latch E. K.
Published: May 2021

Catastrophic population declines due to disease often lead to fragmented remnant populations and loss of gene flow. Managers are left to determine appropriate conservation actions to recover and maintain population persistence. The recent utilization of genomic data to assist in species recovery now allows us to combine genome‐wide surveys of differentiation and diversity with the identification of potentially adaptive regions to develop conservation plans that incorporate ecological and evolutionary processes. The unprecedented global decline of amphibian populations due to the pathogen Batrachochytrium dendrobatidis has increased the need to apply genomic tools to amphibian conservation practices. We show here how understanding genetic characteristics of remnant frog populations affected by disease can be applied directly to restoration efforts. Cascades frogs (Rana cascadae) occur in the mountainous regions of the Pacific northwestern United States and have declined dramatically at the southern edge of their range in California. We conducted genome‐wide surveys within this region to inform conservation and reintroduction efforts. We found strong north‐south genetic differentiation between Oregon and California and novel spatial structure within California. Genetic diversity was lower in California than Oregon and genetic drift was the most important driver of genetic diversity and population structure in California, making conservation efforts aimed at boosting overall genetic diversity most urgent. Spatial genetic structure of populations within California suggests that reintroductions to Lassen Volcanic National Park, where they were recently extirpated, should use remaining source populations south of the park. Our findings support the treatment of California's R. cascadae populations separately from the rest of their range and highlight the importance of conservation genomics in applied species conservation.
Health, economic, and social implications of COVID‐19 for China's rural population
Authors: Wang Huan , Dill Sarah‐Eve , Zhou Huan , Ma Yue , Xue Hao , Sylvia Sean , Smith Kumi , Boswell Matthew , Medina Alexis , Loyalka Prashant , Abby Cody , Friesen Dimitris , Rose Nathan , Guo Yian , Rozelle Scott
Published: May 2021

This study examines the effects of local and nationwide COVID‐19 disease control measures on the health and economy of China's rural population. We conducted phone surveys with 726 randomly selected village informants across seven rural Chinese provinces in February 2020. Four villages (0.55%) reported infections, and none reported deaths. Disease control measures had been universally implemented in all sample villages. About 74% of informants reported that villagers with wage‐earning jobs outside the village had stopped working due to workplace closures. A higher percentage of rural individuals could not work due to transportation, housing, and other constraints. Local governments had taken measures to reduce the impact of COVID‐19. Although schools in all surveyed villages were closed, 71% of village informants reported that students were attending classes online. Overall, measures to control COVID‐19 appear to have been successful in limiting disease transmission in rural communities outside the main epidemic area. Rural Chinese citizens, however, have experienced significant economic consequences from the disease control measures.
Innovative robust basophil activation test using a novel gating strategy reliably diagnosing allergy with full automation
Authors: Behrends Jochen , Schwager Christian , Hein Martina , Scholzen Thomas , Kull Skadi , Jappe Uta
Published: May 2021

Background

Allergy is one of the most common chronic diseases in Europe. Therefore, an increased need for specific and sensitive diagnostic tests that truly detect allergy exists. This study aimed at establishing a highly specific high‐throughput and automated basophil activation test (BAT) that proves the existence of an allergy with utmost probability.

Methods

BAT from 1104 samples was analyzed; a novel gating strategy with three antibodies (FcεRIα, CD203c, CD63) was established and compared with our published protocol (12 antibodies). Based on the novel gating strategy, storage conditions, automated measurement, and analyses using R (1376 samples out of 1389) were optimized to set up a high‐throughput BAT.

Results

No differences in sensitivity and specificity were found between the novel three antibody (FcεRIα, CD203c, CD63) and the 12 antibody gating strategy or between automated and manually analyzed samples (saving up to 90% of labor time). The time frame for basophil activation measurement after blood donation has been extended considerably (whole blood storage ≤7 days (RT) and 17 days (4°C) prior to BAT preparation and measurement). Respective storage conditions were optimized for samples after stimulation, staining, and preparation (≤7 days (RT) and 28 days (4°C)). These achievements were confirmed by a nationwide ring trial showing robustness and applicability of our BAT on a variety of flow cytometers.

Conclusion

Our considerable optimizations overcame the hurdles that until now prevented the BAT from being used as high‐throughput allergy diagnostic test in routine laboratories and shall allow for collaborative studies between clinics and research centers.
Systematic review confirmed the benefits of early skin‐to‐skin contact but highlighted lack of studies on very and extremely preterm infants
Authors: Gupta Nidhi , Deierl Aniko , Hills Emily , Banerjee Jayanta
Published: May 2021

Aim

We systematically reviewed the literature to identify the benefits of early skin‐to‐skin contact (SSC) for all gestational ages.

Methods

The MEDLINE, Embase and CINAHL databases were searched for papers published in English from 1 January 1975 to 31 March 2020. Early SSC was defined as when the infant was placed directly onto the mother's chest within 180 min of birth. Two authors independently searched the databases, appraised study quality and extracted the study design and outcome data. The primary outcomes were the infants’ physiological stability after birth: thermoregulation and stabilisation. The secondary outcomes were exclusive breastfeeding and mother‐infant interaction.

Results

We reviewed 30 studies that assessed the benefits of early SSC: 22 comprised term‐born healthy infants and eight focused on preterm or ill infants. These included various gestational ages, birth methods and cultural backgrounds. The studies demonstrated that early SSC stabilised neonatal physiological parameters, promoted exclusive breastfeeding and supported bonding. Most of the data were from term and late preterm births.

Conclusion

This systematic review showed that early SSC could be beneficial. Further studies that focus on providing very and extremely preterm infants with SSC, and parental experiences, are needed to enable SSC to be adopted as routine practice.
Complementary variable‐ and person‐centred approaches to the dimensionality of workaholism
Authors: Gillet Nicolas , Morin Alexandre J. S. , Ndiaye Adama , Colombat Philippe , Sandrin Emilie , Fouquereau Evelyne
Published: May 2021

This research relies on complementary variable‐ and person‐centred approaches to investigate the underlying dimensionality of the workaholism construct. In three studies (Study 1: N = 343 workers; Study 2: N = 654 firefighters in Sample 1 and N = 247 administrative and technical employees in Sample 2; and Study 3: N = 153 nurses in Sample 1 and N = 359 educators in Sample 2), the results showed that employees' workaholism ratings simultaneously reflected a global overarching workaholism construct, which co‐existed with two specific dimensions (working excessively and compulsively). In Study 1, global levels of self‐determined motivation were associated with higher global levels of workaholism, whereas perceived supervisor support was negatively related to global levels of workaholism. We then examined the distinct configurations, or profiles, taken by workaholism dimensions (global workaholism, and specific working excessively and compulsively; Studies 2 and 3) and psychological detachment (Study 3). Studies 2 and 3 also documented the associations between these workaholism profiles, and correlated predictor (e.g. supervisor support, workload) and outcome (e.g. emotional exhaustion, work performance) variables. Three of the four profiles identified were similar across studies (Low Global and Average Specific Workaholism,Average Global and Specific Workaholism and High Global and Average Specific Workaholism), whereas one profile was different across studies and samples. In both studies, the High Global and Average Specific Workaholism profile was associated with the worst correlated outcome variables (e.g. high levels of emotional exhaustion, low levels of job satisfaction).
Effect of alfalfa (Medicago sativa L.) saponins on meat color and myoglobin reduction status in the longissimus thoracis muscle of growing lambs
Authors: Liu Ce , Xu Chen‐chen , Qu Yang‐hua , Guo Ping‐ting , Ma Yong , Wang Bo , Zhang Hao , Luo Hai‐ling
Published: May 2021

The effect of alfalfa saponins (AS) supplementation on the meat quality especially the color for growing lamb was investigated. Fifty Hu male lambs with body weights (BW, 19.21 ± 0.45 kg) were divided into five groups and supplemented AS with 0, 500, 1,000, 2,000, and 4,000 mg/kg of dietary dry matter intake. After 90 days, all lambs were slaughtered. The longissimus thoracis muscle in lamb displayed significant changes in the content of intramuscular fat, especially n‐3 polyunsaturated fatty acids, and drip loss within AS treatment (p < .05) between control and treatments groups. Redness (a*) significantly improved in both 0‐day and 7‐day storage with the AS supplementation coupled with the percentage of met‐myoglobin reduction (p < .05). The redness (a*) change may result from improved met‐myoglobin reducing activity, antioxidant enzymes, lactate dehydrogenase, and succinate dehydrogenase (p < .05) by AS supplementation in muscle. These enzymes may help to protect mitochondria function and reduce met‐myoglobin, which bring a bright and red meat color.
How do standard setters define materiality and why does it matter?
Authors: Clark Cynthia E.
Published: May 2021

Material information is a core aspect of a firm's governance and reporting activities. If corporate information is material, then the firm has a responsibility to disclose it. Currently, firms must judge information as material largely based on a confusing set of standard setters’ definitions. I analyze the particular conditions laid out by each standard setter and explain the ethical implications that result from materiality judgments made by firms using these varied standards. Importantly, this analysis underscores that regulators, firms, and researchers alike must consider the impact of these implications on the fiduciary duty and promise‐keeping that firms make as well as the potential for unfairness and financial harm to others’ welfare that could result.
Vulnerable groups and the hollow promise of benefit from human gene editing
Authors: Tonkens Ryan
Published: May 2021

Mainstream academic debate on the ethics of human gene editing is currently not as inclusive as it should be. For example, it currently does not give due consideration to Indigenous groups and cultures, such as those living in rural and remote areas of Canada. Once such people are given due consideration, then several important points emerge, which have so far gone unnoticed or under‐emphasized in the debate. This article focuses on two of those points: (a) Some vulnerable people who are currently being ignored in the debate may not desire to use gene editing, even if it is safe, effective and affordable, and they will have compelling reasons for making this decision; and (b) even if such people do decide to use the technology, the gene editing enterprise itself is unlikely to do much good for them (and may even be harmful to them), as it alarmingly misses the point regarding the underlying contributing causes of the most pressing problems that those people are facing. Therefore, the promise of the gene editing enterprise is a hollow one for some groups of vulnerable people. These considerations should be used more prominently to guide debate on the ethics of human gene editing.
Characterisation and application of recombinant FVIII‐neutralising antibodies from haemophilia A inhibitor patients
Authors: Coxon Carmen H. , Yu Xinren , Beavis James , Diaz‐Saez Laura , Riches‐Duit Andrew , Ball Chris , Diamond Scott L. , Raut Sanj
Published: May 2021

The development of anti‐drug antibodies (ADAs) is a serious outcome of treatment strategies involving biological medicines. Coagulation factor VIII (FVIII) is used to treat haemophilia A patients, but its immunogenicity precludes a third of severe haemophiliac patients from receiving this treatment. The availability of patient‐derived anti‐drug antibodies can help us better understand drug immunogenicity and identify ways to overcome it. Thus, there were two aims to this work: (i) to develop and characterise a panel of recombinant, patient‐derived, monoclonal antibodies covering a range of FVIII epitopes with varying potencies, kinetics and mechanism of action, and (ii) to demonstrate their applicability to assay development, evaluation of FVIII molecules and basic research. For the first objective we used recombinant antibodies to develop a rapid, sensitive, flexible and reproducible ex vivo assay that recapitulates inhibitor patient blood using blood from healthy volunteers. We also demonstrate how the panel can provide important information about the efficacy of FVIII products and reagents without the need for patient or animal material. These materials can be used as experimental exemplars or controls, as well as tools for rational, hypothesis‐driven research and assay development in relation to FVIII immunogenicity and FVIII‐related products.
Regulation and Quality Assurance Agencies of Higher Education in Mexico
Authors: Hernández‐Fernández Jimena , Pérez‐Durán Ixchel , Portugal‐Celaya Bolivar
Published: May 2021

This article examines the quality assurance (QA) regime of higher education (HE) in Mexico. In particular, we examine how the regulatory framework of HE quality has evolved in the past three decades and the different regulatory configurations and policy instruments used by QA agencies. We argue that the Mexican case is illustrative of a (weak) hybrid regulatory model that combines the policy instruments of both a state‐centred model and a market‐oriented model. Our results show diverse institutional patterns in the evaluation and accreditation of both public and private institutions.
Inhaled bacteriophage therapy in a porcine model of pneumonia caused by Pseudomonas aeruginosa during mechanical ventilation
Authors: Guillon Antoine , Pardessus Jeoffrey , L'Hostis Guillaume , Fevre Cindy , Barc Celine , Dalloneau Emilie , Jouan Youenn , Bodier‐Montagutelli Elsa , Perez Yonatan , Thorey Camille , Mereghetti Laurent , Cabrera Maria , Riou Mickaël , Vecellio Laurent , Le Guellec Sandrine , Heuzé‐Vourc'h Nathalie
Published: May 2021

Background and Purpose 255

Pseudomonas aeruginosa is a main cause of ventilator‐associated pneumonia (VAP) with drug‐resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of pneumonia caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized‐phage therapy.

Experimental Approach

(i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled‐phage therapy was evaluated in pigs, which were anaesthetized, mechanically ventilated and infected with P. aeruginosa.

Key Results

By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5‐log reduction, p < .001). No infective phage was detected in the sera and urines throughout the experiment.

Conclusion and Implications

Our findings demonstrated (i) the feasibility of delivering large amounts of active phages by nebulization during mechanical ventilation and (ii) rapid control of in situ infection by inhaled bacteriophage in an experimental model of P. aeruginosa pneumonia with high translational value.
Inactivation of soluble guanylyl cyclase in living cells proceeds without loss of haem and involves heterodimer dissociation as a common step
Authors: Dai Yue , Stuehr Dennis J.
Published: May 2021

Background and Purpose

Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) for cGMP production, but in disease, sGC becomes insensitive towards NO activation. What changes occur to sGC during its inactivation in cells is not clear.

Experimental Approach

We utilized HEK293 cells expressing sGC proteins to study the changes that occur regarding its haem content, heterodimer status and sGCβ protein partners when the cells were given the oxidant ODQ or the NO donor NOC12 to inactivate sGC. Haem content of sGCβ was monitored in live cells through use of a fluorescent‐labelled sGCβ construct, whereas sGC heterodimer status and protein interactions were studied by Western blot analysis. Experiments with purified proteins were also performed.

Key Results

ODQ‐ or NOC12‐driven inactivation of sGC in HEK293 cells was associated with haem oxidation (by ODQ), S‐nitrosation of the sGCβ subunit (by NOC12), sGC heterodimer breakup and association of the freed sGCβ subunit with cell chaperone Hsp90. These changes occurred without detectable loss of haem from the sGCβ reporter construct. Treating a purified ferrous haem‐containing sGCβ with ODQ or NOC12 caused it to bind with Hsp90 without showing any haem loss.

Conclusion and Implications

Oxidative (ODQ) or nitrosative (NOC12) inactivation of cell sGC involves sGC heterodimer dissociation and rearrangement of the sGCβ protein partners without any haem loss from sGCβ. Clarifying what changes do and do not occur to sGC during its inactivation in cells may direct strategies to preserve or recover NO‐dependent cGMP signalling in health and disease.

LINKED ARTICLES

This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
To enhance function, promote children’s development
Authors: Rosenbaum Peter
Published: May 2021

Video Podcast: https://youtu.be/O2lvW3JPHYY
Watchwords for management of developmental disabilities in developing countries
Authors: Johari Ashok N
Published: May 2021

Video Podcast: https://youtu.be/rsdn6p75c28
Warming threatens habitat suitability and breeding occupancy of rear‐edge alpine bird specialists
Authors: de Gabriel Hernando Miguel , Fernández‐Gil Juan , Roa Isabel , Juan Jara , Ortega Fernando , de la Calzada Francisco , Revilla Eloy
Published: May 2021

Alpine ecosystems are particularly vulnerable to climate change. For widely distributed alpine specialists, rear‐edge populations are disproportionately important; it is expected that climate change will reduce their occupancy ranges due to the loss of suitable habitats and connectivity among them. Using four alpine bird species inhabiting the southwestern Palearctic as models, we aim to study which and how environmental factors influence habitat suitability, identify mountain areas with suitable habitat, estimate the probabilities of hosting breeding populations for these areas, and predict how habitat suitability and breeding occupancy will change under future climate scenarios. We used a species distribution modeling approach to obtain habitat suitability maps for four biological seasons and assessed the importance and effects of climatic and landscape variables for the studied species. We also assessed the probability of occupancy of potential breeding patches using available systematic distribution data, and projected our habitat suitability and occupancy models to future climate conditions. Our results indicated that the habitat suitability of rear‐edge alpine specialists was limited mainly by climatic factors, restricting their suitable areas to the highest mountains where cold climate persist. The actual occupancy of the potential breeding patches was determined by their size, landscape connectivity and habitat quality. For the period 2041–2060 we predicted a substantial reduction of suitable habitats that varied across seasons and species, and a breeding occupancy range loss that varied across mountain ranges and species. Thus, these alpine bird species, currently not considered as threatened, merit a review of their conservation status. Common distribution patterns and potentially similar responses to climatic change suggest that our findings might be applicable for other rear‐edge alpine species. Our study identified specific mountain systems where research and conservation efforts should focus for the conservation of alpine biodiversity in the southwestern Palearctic.
From deep roots to new blooms: The ever‐growing field of evo–devo across land plants
Authors: Smith Stacey D. , Blackman Benjamin K.
Published: May 2021

Highlights

This editorial synthesizes the contribution of the articles in the special issue on plant evo‐devo to our understanding of major themes, such as the evolution of developmental signaling, the co‐option and modification of shared genetic toolkits, and the link between microevolution and macroevolution.