bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Regulation of the Cytotoxic Activity of Natural Killer Cells
Authors: Mordechay L. , Le Saux G. , Edri A. , Hadad U. , Porgador A. , Schvartzman M.
Published: March 2020

Mechanosensing has been recently explored for T cells and B cells and is believed to be part of their activation mechanism. Here, we explore the mechanosensing of the third type of lymphocytes – Natural Killer (NK) cells, by showing that they modulate their immune activity in response to changes in the stiffness of a stimulating surface. Interestingly, we found that this immune response is bell-shaped, and peaks for a stiffness of a few hundreds of kPa. This bell-shape behavior was observed only for surfaces functionalized with the activating ligand MHC class I polypeptide-related sequence A (MICA), but not for control surfaces lacking immunoactive functionalities. We found that stiffness does not affect uniformly all cells but increases the size of a little group of extra-active cells, which in turn contribute to the overall activation effect of the entire cell population. We further imaged the clustering of costimulatory adapter protein DAP10 on NK cell membrane and found that it shows the same bell –shape dependence to surface stiffness. Based on these findings, we propose a catch-bond-based model for the mechanoregulation of NK cell cytotoxic activity, through interaction of NKG2D activating receptors with MICA. Our findings reveal what seems to be “the tip of iceberg” of mechanosensation of NK cells, and provides an important insight on the mechanism of their immune signaling.

Statement of Significance

The mechanical sensing of immune lymphocytes was recently demonstrated for T cells and B cells, but not for the third type of lymphocytes – Natural Killer (NK) cells. Interestingly, previous reports on lymphocyte mechanosensing were controversial, and showed either positive or negative changes in their immune activity with environmental stiffness, depending on the stiffness range. In this paper, we directly demonstrated that NK cells modulate their response with the stiffness of the stimulating surface, and this modulation has a bell-shape trend. We found that there is a strong correlation between the response to stiffness and clustering of adaptor proteins. Upon this correlation, we proposed a mechanosensing model based on the catch-bond nature of activating ligand-receptor complexes in NK cells.
Natural variation in a glucuronosyltransferase modulates propionate sensitivity in aC. eleganspropionic acidemia model
Authors: Na Huimin , Zdraljevic Stefan , Tanny Robyn E. , Walhout Albertha J.M. , Andersen Erik C.
Published: March 2020

Mutations in human metabolic genes can lead to rare diseases known as inborn errors of human metabolism. For instance, patients with loss-of-function mutations in either subunit of propionyl-CoA carboxylase suffer from propionic acidemia because they cannot catabolize propionate, leading to its harmful accumulation. Interestingly, both the penetrance and expressivity of metabolic disorders can be modulated by genetic background. However, modifiers of these diseases are difficult to identify because of the lack of statistical power for rare diseases in human genetics. Here, we use a model of propionic acidemia in the nematodeCaenorhabditis elegansto identify genetic modifiers of propionate sensitivity. By genome-wide association mapping across wild strains exposed to excess propionate we identify several genomic regions correlated with reduced propionate sensitivity. We find that natural variation in the putative glucuronosyltransferase GLCT-3, a homolog of human B3GAT, partly explains differences in propionate sensitivity in one of these genomic intervals. Using genome-editing, we demonstrate that loss-of-function alleles inglct-3render the animals less sensitive to propionate. Additionally, we find thatC. eleganshas an expansion of theglctgene family, suggesting that the number of members of this family could influence sensitivity to excess propionate. Our findings demonstrate that natural variation in metabolic genes that are not directly associated with propionate breakdown can modulate propionate sensitivity. Our study provides a framework for usingC. elegansto characterize the contributions of genetic background to inborn errors in human metabolism.
Visibility Graph Based Community Detection for Biological Time Series
Authors: Zheng Minzhang , Domanskyi Sergii , Piermarocchi Carlo , Mias George I.
Published: March 2020

Motivation

Temporal behavior is an essential aspect of all biological systems. Time series have been previously represented as networks. Such representations must address two fundamental problems: (i) How to create the appropriate network to reflect the characteristics of biological time series. (ii) How to detect characteristic temporal patterns or events as network communities. General methods to detect communities have used metrics to compare the connectivity within a community to the connectivity one would expect in a random model, or assumed a known number of communities, or are based on the betweenness centrality of edges or nodes. However, such methods were not specifically designed for network representations of time series. We introduce a visibility-graph-based method to build networks from different kinds of biological time series and detect temporal communities within these networks.

Results

To characterize the uneven sampling of typical experimentally obtained biological time series, and simultaneously capture events associated to peaks and troughs, we introduce the Weighted Dual-Perspective Visibility Graph (WDPVG) for time series. To detect communities, we first find the shortest path of the network between start and end nodes to identify nodes which have high intensities. This identifies the main stem of our community detection algorithm. Then, we aggregate nodes outside the shortest path to the nodes found on the main stem based on the closest path length. Through simulation, we demonstrate the validity of our method in detecting community structures on various networks derived from simulated time series. We also confirm its effectiveness in revealing temporal communities in experimental biological time series. Our results suggest our method of visibility graph based community detection can be effective in detecting temporal biological patterns.

Availability

The methods of building WDPVG and visibility graph based community detection are available as a module of the open source Python package PyIOmica (https://doi.org/10.5281/zenodo.3691912) with documentation athttps://pyiomica.readthedocs.io/en/latest/. The dataset and codes we used in this manuscript are publicly available athttps://doi.org/10.5281/zenodo.3693984.

Contact

gmias@msu.edu
Plant origin determines seed mass, seed nutrients and germination behavior of a dominant grass species
Authors: Veselá Andrea , Duongová Lien , Münzbergová Zuzana
Published: March 2020

Although number of studies exploring effects of climate change on plants is increasing, only few studies pay attention to germination. Understanding of germination behaviour is complicated by impact of climate on seed mass and possibly also seed nutrients, which play irreplaceable role in nourishing the sprout. The germination behaviour of species may also depend on trade-off between generative and vegetative reproduction.

We studied Festuca rubra originating from localities situated along a natural climatic grid. Seeds of different origin were germinated in two temperature and two moisture regimes, simulating the extremes of the grid. To study relationship between generative and vegetative reproduction we used data on vegetative traits originating from the same study system.

Seed mass and nutrient concentrations (nitrogen and phosphorus) were significantly affected by original climate, while carbohydrates not. Higher seed mass and warm temperature of origin caused higher and faster germination. Warm and dry condition during germination caused the lowest germination but the highest seed viability. Total germination and proportion of viable seeds negatively correlated with plant performance variables contributing to vegetative reproduction. Despite this, the patterns detected using datasets of germination and plant performance, did not provide fully comparable results.

Simulated changes in climatic condition can modify seed mass and seed nutrients and these changes translate into changes in species germination behavior. After accounting for seed mass, both original and target conditions determine species germination indicating that both genetic differentiation as well as actual conditions drive the germination patterns. As the patterns detected at the level of seed germination do not fully match those detected for the vegetative traits, we urge that future studies should focus on multiple stages of plant life to understand species responses to future climates.
Molecular determinants and heterogeneity of tissue-resident memory CD8+T lymphocytes revealed by single-cell RNA sequencing
Authors: Kurd Nadia S. , He Zhaoren , Milner J. Justin , Omilusik Kyla D. , Louis Tiani L. , Tsai Matthew S. , Widjaja Christella E. , Kanbar Jad N. , Olvera Jocelyn G. , Tysl Tiffani , Quezada Lauren K. , Boland Brigid S. , Huang Wendy J. , Murre Cornelis , Goldrath Ananda W. , Yeo Gene W. , Chang John T.
Published: March 2020

During an immune response to microbial infection, CD8+T cells give rise to distinct classes of cellular progeny that coordinately mediate clearance of the pathogen and provide long-lasting protection against reinfection, including a subset of non-circulating tissue-resident memory (TRM) cells that mediate potent protection within non-lymphoid tissues. Here, we utilized single-cell RNA-sequencing to examine the gene expression patterns of individual CD8+T cells in the spleen and small intestine intraepithelial lymphocyte (siIEL) compartment throughout the course of their differentiation in response to viral infection. These analyses revealed previously unknown transcriptional heterogeneity within the siIEL CD8+T cell population at several states of differentiation, representing functionally distinct TRMcell subsets as well as a subset of TRMcell precursors within the tissue early in infection. Taken together, these findings may inform strategies to optimize CD8+T cell responses to protect against microbial infection and cancer.

One sentence summary

Here, we applied single-cell RNA-sequencing to elucidate the gene expression patterns of individual CD8+T cells differentiating throughout the course of infection in the spleen and small intestinal epithelium, which revealed previously unidentified molecular determinants of tissue-resident T cell differentiation as well as functional heterogeneity within the tissue-resident CD8+T cell population.
Differential neural plasticity of individual fingers revealed by fMRI neurofeedback
Authors: Oblak Ethan , Lewis-Peacock Jarrod , Sulzer James
Published: March 2020

Previous work has shown that fMRI activity patterns associated with individual fingers can be shifted by temporary impairment of the hand. Here, we investigated whether these neural activity patterns could be modulated endogenously and whether any behavioral changes result from this modulation. We used decoded neurofeedback in healthy individuals to encourage participants to shift the neural activity pattern in sensorimotor cortex of the middle finger towards the index finger, and the ring finger towards the little finger. We first mapped the neural activity patterns for all fingers of the right hand in an fMRI pattern localizer session. Then, in three subsequent neurofeedback sessions, participants were rewarded after middle/ring finger presses according to their activity pattern overlap during each trial. A force-sensitive keyboard was used to ensure that participants were not altering their physical finger coordination patterns. We found evidence that participants could learn to shift the activity pattern of the ring finger but not of the middle finger. Increased variability of these activity patterns during the localizer session was associated with the ability of participants to modulate them using neurofeedback. Participants also showed an increased preference for the ring finger but not for the middle finger in a post-neurofeedback motor task. Our results show that neural activity and behaviors associated with the ring finger are more readily modulated than those associated with the middle finger. These results have broader implications for rehabilitation of individual finger movements, which may be limited or enhanced by individual finger plasticity after neurological injury.
Speed and strength of an epidemic intervention
Authors: Dushoff Jonathan , Park Sang Woo
Published: March 2020

An epidemic can be characterized by its speed (i.e., the exponential growth rater) and strength (i.e., the reproductive number ℛ). Disease modelers have historically placed much more emphasis on strength, in part because the effectiveness of an intervention strategy is typically evaluated on this scale. Here, we develop a mathematical framework for this classic, strength-based paradigm and show that there is a corresponding speed-based paradigm which can provide complementary insights. In particular, we note thatr= 0 is a threshold for disease spread, just like ℛ = 1, and show that we can measure the speed and strength of an intervention on the same scale as the speed and strength of an epidemic, respectively. We argue that, just as the strength-based paradigm provides the clearest insight into certain questions, the speed-based paradigm provides the clearest view in other cases. As an example, we show that evaluating the prospects of “test-and-treat” interventions against the human immunodeficiency virus (HIV) can be done more clearly on the speed than strength scale, given uncertainty in the proportion of HIV spread that happens early in the course of infection. We suggest that disease modelers should avoid over-emphasizing the reproductive number at the expense of the exponential growth rate, but instead look at these as complementary measures.
iHyd-ProSite: A novel Computational Approach for Identifying Hydroxylation Sites in Proline Via Mathematical Modeling
Authors: Mahmood Muhammad Khalid , Ehsan Asma , Khan Yaser Daanial
Published: March 2020

In various cellular functions, post translational modifications (PTM) of protein play a vital role. The addition of certain functional group through a covalent bond to the protein induces PTM. The number of PTMs are identified which are closely linked with diseases for example cancer and neurological disorder. Hydroxylation is one of the PTM, modified proline residue within a polypeptide sequence. The defective hydroxylation of proline causes absences of ascorbic acid in human which produce scurvy, and many other dominant health issues. Undoubtedly, the prediction of hydroxylation sites in proline residues is of challenging frontier. The experimental identification of hydroxyproline site is quite difficult, high-priced and time-consuming. The diversity in protein sequences instigates to develop a computational tool to identify hydroxylated site within short time with excellent prediction accuracy to handle such proteomics problems. In this work a novel in silico predictor is developed through rigorous mathematical modeling to identify which site of proline is hydroxylated and which site is not? Then performance of the predictor was verified using three validations tests, namely self-consistency test, cross-validation test and jackknife test over the benchmark dataset. A comparison was established for jackknife test with the previous methods. In comparison with previous predictors the proposed tool is more accurate than the existing techniques. Hence this scheme is highly useful and inspiring in contrast to all previous predictors.
Regulation of gene expression by repression condensates during development
Authors: Treen Nicholas , Shimobayashi Shunsuke F. , Eeftens Jorine , Brangwynne Clifford P. , Levine Michael S.
Published: March 2020

There is emerging evidence for transcription condensates in the activation of gene expression1–3. However, there is considerably less information regarding transcriptional repression, despite its pervasive importance in regulating gene expression in development and disease. Here, we explore the role of liquid-liquid phase separation (LLPS) in the organization of the Groucho/TLE (Gro) family of transcriptional corepressors, which interact with a variety of sequence-specific repressors such as Hes/Hairy4. Gro-dependent repressors have been implicated in a variety of developmental processes, including segmentation of theDrosophilaembryo and somitogenesis in vertebrates. These repressors bind to specific recognition sequences, but instead of interacting with coactivators (e.g., Mediator) they recruit Gro corepressors5. Gro contains a series of WD40 repeats that are thought to mediate oligomerization6. How putative Hes/Gro oligomers repress transcription has been the subject of numerous studies5, 6. Here we show that Hes/Gro complexes form discrete puncta within nuclei of livingCionaembryos. These puncta rapidly dissolve during the onset of mitosis and reappear in the ensuing cell cycle. Modified Hes/Gro complexes that are unable to bind DNA exhibit the properties of viscous liquid droplets, similar to those underlying the biogenesis of P-granules inC. elegans7and nucleoli inXenopusoocytes8. These observations provide vivid evidence for LLPS in the control of gene expression and suggest a simple physical exclusion mechanism for transcriptional repression. WD40 repeats have been implicated in a wide variety of cellular processes in addition to transcriptional repression9. We suggest that protein interactions using WD40 motifs might be a common feature of processes reliant on LLPS.
Examining user experience of eLearning systems implemented in two universities in Tanzania
Authors: Mtebe Joel S.
Published: March 2020

Purpose

This study aims to investigate the factors that influence user experience (UX) of eLearning systems implemented in two institutions in Tanzania.

Design/methodology/approach

The study adopted questionnaire consisting of Nielsen’s heuristics and didactic metrics as pragmatic metrics and hedonic metrics followed by focus group discussions with students.

Findings

The study found that the eLearning system of University of Dar es Salaam had 43 UX problems related to Nielsen’s heuristics and 54 UX problems related to didactic heuristics. The eLearning system of the Open University of Tanzania had 50 UX problems related to Nielsen’s heuristics and 59 UX problems related to didactic heuristics. Moreover, the two systems provided positive UX hedonic quality on identification and evocation dimensions while stimulation was perceived to be neutral.

Research limitations/implications

The study has used learners as evaluators rather than expert evaluators. Learners are not particularly experienced in the learning domain, and therefore, it is difficult for them to identify many didactic violations of the eLearning systems.

Originality/value

The study contributes toward finding the underlying factors for non-use or underuse of the installed eLearning systems in various universities in sub-Saharan Africa.
Sustainability of the rice-shrimp farming system in Mekong Delta, Vietnam: a climate adaptive model
Authors: Dang Huy Duc
Published: March 2020

Purpose

Agricultural systems in Mekong Delta have transformed to cope with climate change. Various researches pointed out that integrated agriculture-aquaculture (IAA) farming systems (i.e., rice-shrimp, rice-fish…) emerged as potential climate adaptive practices. However, limited studies are attempting to assess the sustainability of these agricultural practices. Therefore, it is essential to assess whether or not these systems will be sustainable in the context of climate change and what can be done to make it sustainable. The present study conducted the sustainability assessment of the rice-shrimp system to identify potential areas for improvement as well as policy implication to increase resilience and adaptation of coastal IAA system which could contribute to the understanding of other coastal agricultural deltas around the globe.

Design/methodology/approach

This study used a quantitative approach including the assessment protocol of van Asselt et al. (2014), the assessment framework of Vanloon et al. (2005), and the MCA methodology to flexibly and holistically assess the sustainability level of agricultural systems.

Findings

Results concluded that rice-shrimp systems have the potential to improve livelihood, food security, and adaptation of coastal farmers. Major improvements should be considered for productivity, efficiency, and equity themes, while minor improvements can be made for stability, durability, and compatibility themes.

Originality/value

This research could be used as a guideline for sustainability assessment in a context-specific case study of IAA, which showed a potential for the application of other climate-smart IAAs in similar contexts around the globe.
Economic growth and quality of institutions in 27 postsocialist economies
Authors: Alexiou Constantinos , Vogiazas Sofoklis , Solovev Nikita
Published: March 2020

Purpose

The relationship between institutional quality and economic growth is revisited.

Design/methodology/approach

A panel cointegration methodology and causality analysis are applied to 27 postsocialist economies over the period from 1996 to 2016.

Findings

Utilizing the Worldwide Governance Indicators as a means of assessing the quality of institutions, it is found that in the long run, economic growth is positively associated with the rule of law and voice and accountability. In the short run, regulatory quality retains a positive effect, but voice and accountability demonstrate a puzzling negative effect on economic growth that merits further analysis. In exploring the causal dimension of our variables, supporting evidence of the strong links between the quality of institutions and economic growth is provided, hence rendering robust results.

Originality/value

To the best of the authors’ knowledge, it is the first time that an ARDL methodological framework, which addresses potential endogeneity issues, is used to investigate the relationship between institutional quality and growth in the context of postsocialist economies.
A PCA-DEA method for organizational performance evaluation based on intellectual capital and employee loyalty
Authors: Rahimpour Khojasteh , Shirouyehzad Hadi , Asadpour Milad , Karbasian Mehdi
Published: March 2020

Purpose

The purpose of this study is to propose a model to evaluate the performance of organizational units considering intellectual capital (IC) and employee loyalty approach applying principal component analysis and data envelopment analysis (PCA-DEA) method.

Design/methodology/approach

Organization units are considered as decision-making units, IC components including human capital (HC), structural capital (SC) and customer capital are inputs and employee loyalty is output. The principal component analysis was used to converts inputs and outputs into the independent variables. As a return to scale is variable, a modified envelopment input-oriented BCC model applied to obtain the efficiency of organization units. Also, all units of organization are ranked. Eventually, sensitivity analysis performed to show how input variables influence on output variable.

Findings

Operation, design and construction, production planning, internal affairs, quality control and security were recognized as efficient units. Also, units of operation, internal affairs and quality control ranked first to third, and the human resource unit earned the last rank. In addition, results of sensitivity analysis on input variables showed that the order of impact intensity is: customer capital, HC and SC, respectively.

Originality/value

Existence a framework for the development of human resource strategies and prioritization in the allocation of organizational resources to improve the performance of the organization considering human resources is vital. Most of the previous studies, just have examined the impact of IC on different dimensions of organizational performance. Meanwhile, evaluating the performance of IC with employee loyalty approach, using PCA-DEA simultaneously can evaluate and measure the impact of IC on the performance of the organization and its units regarding employee loyalty, which has a significant impact on improving the organization’s level of IC and human resource management.
Innovation and intellectual capital as intermediary variables among transformational leadership, transactional leadership, and organizational performance
Authors: Alrowwad Ala'aldin , Abualoush Shadi Habis , Masa'deh Ra'ed
Published: March 2020

Purpose

The purpose of this paper is to examine the mediating effect of intellectual capital and innovation on the relationship between transformational and transactional leadership and organizational performance in Jordanian banks located in Irbid city.

Design/methodology/approach

A questionnaire that targeted 350 respondents resulted in 298 usable ones with a response rate of 85.14 percent. To test the research hypotheses, a structural equation model was conducted, in addition to descriptive statistics that provided background on the respondents.

Findings

The findings indicate that transformational and transactional leadership relate positively to organizational performance. The results also support the argument that intellectual capital and innovation played mediating roles in transformational and transactional leadership and organizational performance.

Practical implications

The present study provides managers with empirical proof that possessing strong intellectual capital in its three dimensions seems to help the banking sector in Jordan to reinforce their ability to generate both radical and incremental innovation. Also, applying an effective leadership style will motivate and lead to superior performance.

Originality/value

Although papers have shown that leadership style is an important factor influencing employees' performance and outcomes, this is one of the few studies that investigates the interrelationships between leadership styles, intellectual capital, and innovation on organization performance. Furthermore, it is the first to test the model on the banking sector in Jordan.
Vanillin-based thiol-ene systems as photoresins for optical 3D printing
Authors: Navaruckiene Aukse , Kasetaite Sigita , Ostrauskaite Jolita
Published: March 2020

Purpose

This study aims to present a design and investigation of novel vanillin-based thiol-ene photocurable systems as candidate materials for optical three-dimensional printing.

Design/methodology/approach

Two vanillin acrylates, vanillin dimethacrylate and vanillin diacrylate, were tested in thiol-ene photocurable systems with 1,3-benzenedithiol. The kinetics of photocross-linking was investigated by real-time photorheometry using two photoinitiators, diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide or ethyl (2,4,6-trimethylbenzoyl)phenylphosphinate in different quantities. The dependencies of rheological properties of resins on the used vanillin derivative, photoinitiator, and the presence of a solvent, as well as structure, thermal and mechanical properties of the selected polymers were investigated.

Findings

The most rigid polymers were obtained from vanillin diacrylate-based resins without any solvent. The vanillin diacrylate-based polymer possessed higher values of cross-linking density, the yield of insoluble fraction, thermal stability and better mechanical properties in comparison to the vanillin dimethacrylate-based polymer.

Originality/value

The kinetics of photocross-linking of vanillin-based thiol-ene systems was investigated by real-time photorheometry for the first time. The designed novel photocurable systems based on vanillin acrylates and 1,3-benzenedithiol are promising renewable photoresins for optical three-dimensional printing on demand.
Short‐term changes in polysaccharide utilization mechanisms of marine bacterioplankton during a spring phytoplankton bloom
Authors: Reintjes Greta , Fuchs Bernhard M. , Scharfe Mirco , Wiltshire Karen H. , Amann Rudolf , Arnosti Carol
Published: March 2020

Spring phytoplankton blooms in temperate environments contribute disproportionately to global marine productivity. Bloom‐derived organic matter, much of it occurring as polysaccharides, fuels biogeochemical cycles driven by interacting autotrophic and heterotrophic communities. We tracked changes in the mode of polysaccharide utilization by heterotrophic bacteria during the course of a diatom‐dominated bloom in the German Bight, North Sea. Polysaccharides can be taken up in a ‘selfish’ mode, where initial hydrolysis is coupled to transport into the periplasm, such that little to no low‐molecular weight (LMW) products are externally released to the environment. Alternatively, polysaccharides hydrolyzed by cell‐surface attached or free extracellular enzymes (external hydrolysis) yield LMW products available to the wider bacterioplankton community. In the early bloom phase, selfish activity was accompanied by low extracellular hydrolysis rates of a few polysaccharides. As the bloom progressed, selfish uptake increased markedly, and external hydrolysis rates increased, but only for a limited range of substrates. The late bloom phase was characterized by high external hydrolysis rates of a broad range of polysaccharides and reduced selfish uptake of polysaccharides, except for laminarin. Substrate utilization mode is related both to substrate structural complexity and to the bloom‐stage dependent composition of the heterotrophic bacterial community.
Background‐dependentWolbachia‐mediated insecticide resistance inLaodelphax striatellus
Authors: Li Yongteng , Liu Xiangdong , Wang Na , Zhang Yueliang , Hoffmann Ary A. , Guo Huifang
Published: March 2020

Although facultative endosymbionts are now known to protect insect hosts against pathogens and parasitoids, the effects of endosymbionts on insecticide resistance are still unclear. Here we show thatWolbachiaare associated with increased resistance to the commonly used insecticide, buprofezin, in the small brown planthopper (Laodelphax striatellus) in some genetic backgrounds while having no effect in other backgrounds. In threeWolbachia‐infected lines from experimental buprofezin‐resistant strains and one line from a buprofezin‐susceptible line established from Chuxiong, Yunnan province, China, susceptibility to buprofezin increased after removal ofWolbachia. An increase in susceptibility was also evident in aWolbachia‐infected line established from a field population in Rugao, Jiangsu province. However, no increase was evident in two field populations from Nanjing and Fengxian, Jiangsu province, China. WhenWolbachiawas introgressed into different genetic backgrounds, followed byWolbachiaremoval, the data pointed toWolbachiaeffects that depend on the nuclear background as well as on theWolbachiastrain. However, there was no relationship betweenWolbachiadensity and the component of buprofezin resistance associated with the symbiont. The results suggest thatWolbachiaeffects associated with chemical resistance are complex and unpredictable, but also that they can be substantial.
Learning to manage uncertainty: supervision, trust and autonomy in residency training
Authors: Bochatay Naike , Bajwa Nadia M.
Published: March 2020

Sociologists have debated whether and how medical trainees are socialised to deal with uncertainty for decades. Recent changes in the structure of medical education, however, have likely affected the ways that resident physicians learn to manage uncertainty. Through ethnographic case studies of academic medical centres in Switzerland and the United States, this article provides new insights into the processes through which residents learnt to manage uncertainty. These processes included working under supervision, developing relationships of trust with supervisors and gaining autonomy to practise independently. As a result, residents developed different attitudes towards uncertainty. Residents at the Swiss medical centre tended to develop a more pragmatic attitude and viewed uncertainty as something to be addressed and controlled. On the other hand, residents at the American medical centre tended to develop an acceptive attitude towards uncertainty. More broadly, residents learnt to reproduce their supervisors’ attitudes towards uncertainty. This article therefore provides new perspectives on continuity and the reproduction of social phenomena in medical education.
Evidence on the Use and Efficacy of Internal Whistleblowing Systems
Authors: STUBBEN STEPHEN R. , WELCH KYLE T.
Published: March 2020

Using a proprietary data set from a provider of internal whistleblowing (WB) systems, we analyze nearly two million internal WB reports submitted to over 1,000 publicly traded U.S. firms. We provide descriptive statistics, over time and across report types, on the amount and summary details of information provided, how extensively management reviews reports, the amount of time until reviews were completed, and the outcome of these reviews. Further, we examine the characteristics of firms with more actively used systems (i.e., a higher volume of reports, more information provided in reports, and reports that are more frequently reviewed by management). Finally, we show that internal WB report volume is associated with fewer and lower amounts of government fines and material lawsuits.
Occurrence and preventive strategies to control mycotoxins in cereal‐based food
Authors: Wan Jing , Chen Bingcan , Rao Jiajia
Published: March 2020

Mycotoxins contamination in cereal‐based food is ubiquitous according to systematic review of the scientific documentation of worldwide mycotoxin contamination in cereal and their products between 2008 and 2018, thus representing food safety issue especially in developing tropical countries. Food processing plays a vital role to prevent mycotoxin contamination in food. Therefore, it is with great urgency to develop strategies to inhibit fungi growth and mycotoxin production during food processing. This review begins by discussing physicochemical properties of five most common mycotoxins (aflatoxins, fumonisins, ochratoxins, deoxynivalenol, and zearalenone) found in cereal grains, regulation for mycotoxins in food, and their potential negative impact on human health. The fate of mycotoxins during major cereal‐based food processing including milling, breadmaking, extrusion, malting, and brewing was then summarized. In the end, traditional mitigation strategies including physical and chemical and potential application of biocontrol agent and essential oil nanoemulsions that can be applied during food processing were discussed. It indicated that no single method is currently available to completely prevent mycotoxin contamination in cereal foods.
Bioavailability of nutraceuticals: Role of the food matrix, processing conditions, the gastrointestinal tract, and nanodelivery systems
Authors: Dima Cristian , Assadpour Elham , Dima Stefan , Jafari Seid Mahdi
Published: March 2020

Nowadays, many consumers prefer foods with a high content of nutraceuticals that contribute to the prevention or healing of chronic diseases. Therefore, in recent years, more and more researchers have studied the bioefficiency, safety, and toxicity of nutraceutical‐enriched foods. The key stage of nutraceutical bioefficiency is oral bioavailability, which involves the following processes: the release of nutraceuticals from food matrices or nanocarriers in gastrointestinal fluids, the solubilization of nutraceuticals and their interaction with other components of gastrointestinal fluids, the absorption of nutraceuticals by the epithelial layer, and the chemical and biochemical transformations into epithelial cells. These processes are endogenous factors that greatly influence the bioavailability of nutraceuticals. In addition to endogenous factors, the bioavailability of nutraceuticals is also affected by exogenous factors, such as: physicochemical properties of nutraceuticals, food matrix, food processing and storage, and so forth. Both the endogenous and exogenous factors are comprehensively analyzed in this review. Thus, the physicochemical and enzymatic processes involved in food digestion are described, highlighting the role of each stage of gastrointestinal tract (mouth, stomach, and intestine) in nutraceuticals bioaccessibility. The structure and functions of the mucus and epithelial layers, the mechanisms involved in the active and passive transport of nutraceuticals through the cell membrane, and phase I and phase II metabolism reactions are also discussed. Finally, this review focuses on several types of bioactive‐loaded nanocarriers such as lipid‐based, surfactant‐based, and biopolymeric nanocarriers that improve the bioavailability of nutraceuticals.
Chitinase 10 controls chitin amounts and organization in the wing cuticle of Drosophila
Authors: Dong Wei , Gao Ying‐Hao , Zhang Xu‐Bo , Moussian Bernard , Zhang Jian‐Zhen
Published: March 2020

Wings are essential for insect fitness. A number of proteins and enzymes have been identified to be involved in wing terminal differentiation, which is characterized by the formation of the wing cuticle. Here, we addressed the question whether chitinase 10 (Cht10) may play an important role in chitin organization in the wings of the fruit fly Drosophila melanogaster. Initially, we first found that Cht10 expression coincides with the expression of the chitin synthase coding gene kkv. This suggests that the respective proteins may cooperate during wing differentiation. In tissue‐specific RNA interference experiments, we demonstrate that suppression of Cht10 causes an excess in chitin amounts in the wing cuticle. Chitin organization is severely disrupted in these wings. Based on these data, we hypothesize that Cht10 restricts chitin amounts produced by Kkv in order to ensure normal chitin organization and wing cuticle formation. In addition, we found by scanning electron microscopy that Cht10 suppression also affects the cuticle surface. In turn, cuticle inward permeability is enhanced in Cht10‐less wings. Moreover, flies with reduced Cht10 function are unable to fly. In conclusion, Cht10 is essential for wing terminal differentiation and function.
The efficacy of axitinib as a first‐line treatment for metastatic renal cell carcinoma
Authors: Kameda Tomohiro , Takayama Tatsuya , Sugihara Toru , Takeshima Saki , Yamazaki Masahiro , Komatsubara Maiko , Kamei Jun , Fujisaki Akira , Ando Satoshi , Kurokawa Shinsuke , Fujimura Tetsuya
Published: March 2020

Aim

To evaluate predictive factors which associated with oncological outcomes to first‐line axitinib for metastatic renal cell carcinoma (mRCC).

Methods

A retrospective chart review was conducted patients who had been treated with axitinib as first‐line therapy for the treatment of mRCC from September 2013 to February 2018. Axitinib was given by single daily oral administration at a dose of 10 mg, which was reduced according to adverse events (AEs). We investigated progression‐free survival (PFS), overall survival (OS), objective response rate (ORR) and AEs.

Results

Thirty‐eight mRCC patients were enrolled. The median follow‐up duration of axitinib treatment was 11.3 months (range = 1.0–56.9). ORR was 28.9%. Median PFS and OS was 12.8, and 17.9 months, respectively. In univariate analysis, baseline lactate dehydrogenase (LDH), neutrophil, corrected calcium (Ca), platelets (Plt) and time from diagnosis were selected as potential predictive factors. Multivariate Cox's proportional hazards model analysis showed that the number of risk factors were associated with PFS (P = 0.03) and OS (P = 0.02).

Conclusion

Baseline LDH, neutrophil, Ca, Plt and time from diagnosis are predictive factors for both PFS and OS in first‐line treatment with axitinib for metastatic renal cell carcinoma.
Neutrophil count kinetics during the first cycle of chemotherapy predicts the outcome of patients with locally advanced or metastatic pancreatic cancer
Authors: Colloca Giuseppe Antonio , Venturino Antonella , Guarneri Domenico
Published: March 2020

Background

Neutrophil count reduction after chemotherapy has been related with longer survival of patients with metastatic pancreatic adenocarcinoma, but there is not a standardized measurement for this phenomenon.

Methods

Some parameters related to the change in neutrophil count between the first and the second cycle of chemotherapy or between the baseline count and the nadir have been evaluated among patients with advanced pancreatic cancer at a single institution. A Cox regression model was built which included, in addition to the common prognostic variables, some variables related to the change of the neutrophil count after chemotherapy.

Results

One hundred patients were selected. Two neutrophil kinetics related variables predicted overall survival independently, such as the neutrophil count growth rate (hazard ratio [HR] = 1.245; confidence intervals [CIs], 1.077–1.440) and the chemotherapy‐induced neutropenia after one cycle (HR = 0.499; CIs, 0.269–0.927).

Conclusion

The kinetics of neutrophil count after chemotherapy is an early and independent prognostic factor, which appears to be simple to measure at the start of the second cycle of chemotherapy by means of the neutrophil count growth rate.
The rationale and toxicity of combined cranial radiotherapy and immune checkpoint inhibitors in non‐small cell lung cancer
Authors: Chen Yi , Zhuang Hongqing , Wang Junjie
Published: March 2020

Cranial radiation therapy (CRT) remains to be the foundation stone of the management of brain metastases in non‐small cell lung cancer (NSCLC). Nevertheless, the care of NSCLC, recently, has been remarkably reshaped by the immune checkpoint inhibitors (ICIs), such as programmed death protein‐1 and programmed death ligand‐1 inhibitors, which even showed some efficacy in brain metastases. Furthermore, radiotherapy, traditionally regarded as a therapy via localized cytotoxicity, recently was reported to trigger a systemic immune response, thus probably enhancing the antitumor effect of ICIs. Preliminary datasets confirmed that the combination of these two therapies seemed superior to either monotherapy in NSCLC patients with brain metastases with improved efficacy and comparable toxicity. In this review, we started with discussing the rationale for the combination of CRT and ICIs, then outlined the clinical evidence supporting the high safety of this combined therapy, and finally made a preliminary conclusion on the safety of the combination of CRT and ICIs.
Sydney Facial Nerve Clinic: experience of a multidisciplinary team
Authors: Hayler Raymond , Clark Jonathan , Croxson Glen , Coulson Susan , Hussain Gazi , Ngo Quan , Ch'ng Sydney , Low Tsu‐Hui (Hubert)
Published: March 2020

Background

The Sydney Facial Nerve Clinic (SFNC) is a multidisciplinary clinic established in 2015, consisting of surgeons (otolaryngologists, head and neck and plastics/reconstructive), physiotherapists and speech pathologists.

Methods

We reviewed patients who attended the SFNC in the first 3 years and who had their symptoms recorded using the Facial Disability Index, and clinical staging recorded utilising the House–Brackmann (HB) score, Sydney Facial Nerve Score and Sunnybrook Facial Grading System (SFGS).

Results

Between May 2015 and June 2018, 145 patients attended the clinic. Mean age was 44.6 ± 17.3 years with 94 (64.8%) females. Most referrals came from general practitioners (n = 75, 54.5%). The most common aetiology was iatrogenic injury (n = 55, 37.9%), followed by Bell's palsy (n = 48, 33.1%), congenital (n = 11, 7.6%), herpes zoster oticus (n = 9, 6.2%), trauma (n = 9, 6.2%) and other (n = 13, 9.0%). The median HB was 4, the mean Sydney score 7.3/15 and the mean SFGS was 45/100. Patients with iatrogenic causes had the worse facial nerve scoring in HB, Sydney and SFGS. Patients with congenital aetiology reported the least symptoms on Facial Disability Index (P < 0.001). Most patients were recommended non‐surgical management (n = 92, 64.3%); 51 (35.7%) were referred for botulinum toxin + facial physiotherapy, 25 (17.2%) for physiotherapy alone, seven (4.9%) for botulinum toxin alone and nine (6.3%) for conservative management. Fifty‐one patients (35.7%) were recommended surgery, generating 75 procedures; 24 oculoprotective, 22 static, 12 gracilis transfers, 10 temporalis myoplasties and seven nerve transfers.

Conclusion

Iatrogenic injuries are the most common presentation for this clinic and have a more severe clinical presentation. Most patients presenting to the SFNC were managed non‐surgically.
Influence of obesity on the risk of recurrent acute diverticulitis
Authors: Turner Greg A. , O'Grady Michael , Frizelle Frank A. , Eglinton Tim W. , Sharma Prashant V.
Published: March 2020

Background

Acute diverticulitis (AD) is a common surgical problem with increasing incidence. Obesity has become epidemic in western countries. Obesity has been shown to increase the risk of developing AD; however, little is known about its influence on the risk of recurrence. The decision to perform elective surgical resection to reduce the risk of recurrent AD is made on an individual basis considering perceived risk of recurrence weighed against patient comorbidity. The aim of this study is to assess whether obesity affects the likelihood of developing recurrent AD.

Methods

A retrospective audit was conducted of all admissions with AD to a tertiary centre between 1998 and 2010. Medical records were reviewed and patients with an index presentation with AD included in the analysis. Imaging was used to calculate body mass index (BMI) for assessment of obesity. Follow‐up was for a minimum of 3 years from admission.

Results

A total of 1299 patients were admitted with an index presentation of AD in the study period. 18.3% overall had recurrent AD, all of whom had confirmation on imaging. Computed tomography was used to calculate BMI in 849 patients, of whom 470 (55.4%) were considered obese (BMI >30). The likelihood of recurrent AD was not significantly different in obese patients compared to their non‐obese counterparts (P = 0.2473).

Conclusion

While obesity increases the risk of developing AD overall, it does not appear to increase the likelihood of developing recurrent AD. This has implications for risk stratification when considering surgical resection to prevent recurrent AD.