bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension
Authors: Yang Guang , Tan Zihu , Zhou Ling , Yang Min , Peng Lang , Liu Jinjin , Cai Jingling , Yang Ru , Han Junyan , Huang Yafei , He Shaobin
Published: April 2020

With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.
Hematologist-level classification of mature B-cell neoplasm using deep learning on multiparameter flow cytometry data
Authors: Zhao Max , Mallesh Nanditha , Schabath Richard , Höllein Alexander , Haferlach Claudia , Haferlach Torsten , Elsner□ Franz , Lüling□ Hannes , Krawitz Peter , Kern Wolfgang
Published: April 2020

The wealth of information captured by multiparameter flow cytometry (MFC) can be analyzed by recent methods of computer vision when represented as a single image file. We therefore transformed MFC raw data into a multicolor 2D image by a self-organizing map (SOM) and classified this representation using a convolutional neural network (CNN). By this means, we built an artificial intelligence that is not only able to distinguish diseased from healthy samples, but that can also differentiate seven subtypes of mature B-cell neoplasm (B-NHL). We trained our model with 18,274 cases including chronic lymphocytic leukemia (CLL) and its precursor monoclonal B-cell lymphocytosis (MBL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), prolymphocytic leukemia (PL), follicular lymphoma (FL), hairy cell leukemia (HCL), lymphoplasmacytic lymphoma (LPL) and achieved a weighted F1 score of 0.94 on a separate test set of 2,348 cases. Furthermore, we estimated the trustworthiness of a classification and could classify 70% of all cases with a confidence of 0.95 and higher. Our performance analyses indicate that particularly for rare subtypes further improvement can be expected when even more samples are available for training.
Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores
Authors: Coombes Brandon J. , Markota Matej , Mann J. John , Colby Colin , Stahl Eli , Talati Ardesheer , Pathak Jyotishman , Weissman Myrna M. , McElroy Susan L. , Frye Mark A. , Biernacka Joanna M.
Published: April 2020

Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic PRS analysis using multiple polygenic risk scores (PRSs) from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N = 968) and Genetic Association Information Network (N = 1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR = 1.3 per S.D.; p = 3e-5) but lower PRSs for anhedonia (OR = 0.87; p = 0.003) and BMI (OR = 0.87; p = 0.003). Rapid cycling cases had higher PRS for ADHD (OR = 1.23; p = 7e-5) and MDD (OR = 1.23; p = 4e-5) and lower BD PRS (OR = 0.8; p = 0.004). Cases with a suicide attempt had higher PRS for MDD (OR = 1.26; p = 1e-6) and anhedonia (OR = 1.22; p = 2e-5) as well as lower PRS for educational attainment (OR = 0.87; p = 0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity underlies the clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.
Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients
Authors: Herold Tobias , Jurinovic Vindi , Arnreich Chiara , Hellmuth Johannes C. , von Bergwelt-Baildon Michael , Klein Matthias , Weinberger Tobias
Published: April 2020

The pandemic Coronavirus-disease 19 (COVID-19) is characterized by a heterogeneous clinical course. While most patients experience only mild symptoms, a relevant proportion develop severe disease progression with increasing hypoxia up to acute respiratory distress syndrome. The substantial number of patients with severe disease have strained intensive care capacities to an unprecedented level. Owing to the highly variable course and lack of reliable predictors for deterioration, we aimed to identify variables that allow the prediction of patients with a high risk of respiratory failure and need of mechanical ventilation Patients with PCR proven symptomatic COVID-19 infection hospitalized at our institution from 29th February to 27th March 2020 (n=40) were analyzed for baseline clinical and laboratory findings. Patients requiring mechanical ventilation 13/40 (32.5%) did not differ in age, comorbidities, radiological findings, respiratory rate or qSofa score. However, elevated interleukin-6 (IL-6) was strongly associated with the need for mechanical ventilation (p=1.2.10-5). In addition, the maximal IL-6 level (cutoff 80 pg/ml) for each patient during disease predicted respiratory failure with high accuracy (p=1.7.10-8, AUC=0.98). The risk of respiratory failure for patients with IL-6 levels of >; 80 pg/ml was 22 times higher compared to patients with lower IL-6 levels. In the current situation with overwhelmed intensive care units and overcrowded emergency rooms, correct triage of patients in need of intensive care is crucial. Our study shows that IL-6 is an effective marker that might be able to predict upcoming respiratory failure with high accuracy and help physicians correctly allocate patients at an early stage.
Core-periphery structure in mutualistic networks: an epitaph for nestedness?
Authors: Martín González Ana M. , Vázquez Diego P. , Ramos-Jiliberto Rodrigo , Lee Sang Hoon , Miele Vincent
Published: April 2020

The calculation of nestedness has become a routine analysis in the study of ecological networks, as it is commonly associated with community resilience, robustness and species persistence. While meaningful in species distributional patterns, for an interaction matrix to be nested, specialist species must interact with ordered subsets of subsequently more generalized species — not just with a lower number of species. However, after reviewing 419 papers on mutualistic networks published since nestedness was introduced for the study of species interactions in 2003, we have found that only two theoretical studies considered explicitly ordered subsets. Instead, most studies interpret nestedness as a core of densely connected generalist species, surrounded by a periphery of specialist species attached to this core — a so-called core-periphery structure. Such a topological feature is generally perceived as a core-periphery structure in network science. Here, we argue that the concept of core-periphery may be more relevant for studies on mutualistic networks than the concept of nestedness, as ecologists are usually not interested in exploring in detail the ordered subsets that characterize nestedness but instead use nestedness to describe a topology with a core of densely linked generalist species surrounded by a sparsely linked periphery of specialists. To illustrate our arguments and the quantification of core-periphery structures, we calculate core-periphery and nestedness in a large publicly available dataset of mutualistic networks. We also describe the calculation of core-periphery structures, its relationship with nestedness, and provide the code inside the R packageeconetworkfor its calculation in mutualistic networks. We hope that our review will help ecologists to move beyond nestedness towards a more explicit representation of the structure of ecological networks.
Modeling the COVID-19 outbreaks and the effectiveness of the containment measures adopted across countries
Authors: De Brouwer Edward , Raimondi Daniele , Moreau Yves
Published: April 2020

On March 11, 2020, the World Health Organization declared the COVID-19 outbreak, originally started in China, a global pandemic. Since then, the outbreak has indeed spread across all continents, threatening the public health of numerous countries. Although the Case Fatality Rate (CFR) of COVID-19 is relatively low when optimal level of healthcare is granted to the patients, the high percentage of severe cases developing severe pneumonia and thus requiring respiratory support is worryingly high, and could lead to a rapid saturation of Intensive Care Units (ICUs). To overcome this risk, most countries enacted COVID-19 containment measures. In this study, we use a Bayesian SEIR epidemiological model to perform a parametric regression over the COVID-19 outbreaks data in China, Italy, Belgium, and Spain, and estimate the effect of the containment measures on the basic reproduction ratioR0.

We find that the effect of these measures is detectable, but tends to be gradual, and that a progressive strengthening of these measures usually reduces theR0below 1, granting a decay of the outbreak. We also discuss the biases and inconsistencies present in the publicly available data on COVID-19 cases, providing an estimate for the actual number of cases in Italy on March 12, 2020. Lastly, despite the data and model’s limitations, we argue that the idea of “flattening the curve” to reach herd immunity is likely to be unfeasible.
An oscillating MinD protein determines the cellular positioning of the motility machinery in archaea
Authors: Nußbaum Phillip , Ithurbide Solenne , Walsh James C. , Patro Megha , Delpech Floriane , Rodriguez-Franco Marta , Curmi Paul M.G. , Duggin Iain G. , Quax Tessa E.F. , Albers Sonja-Verena
Published: April 2020

MinD proteins are well studied in rod-shaped bacteria such asE. coli, where they display self-organized pole-to-pole oscillations that are important for correct positioning of the Z-ring at mid-cell for cell division. Archaea also encode proteins belonging to the MinD family, but their functions are unknown. MinD homologous proteins were found to be widespread in Euryarchaeota and form a sister group to the bacterial MinD family, distinct from the ParA and other related ATPase families. We aimed to identify the function of four archaeal MinD proteins in the model archaeonHaloferax volcanii. Deletion of theminDgenes did not cause cell division or size defects, and the Z-ring was still correctly positioned. Instead, one of the mutations (ΔminD4) reduced swimming motility, and hampered the correct formation of motility machinery at the cell poles. In ΔminD4cells, there is reduced formation of the motility structure and chemosensory arrays, which are essential for signal transduction. In bacteria, several members of the ParA family can position the motility structure and chemosensory arrays via binding to a landmark protein, and consequently these proteins do not oscillate along the cell axis. However, GFP-MinD4 displayed pole-to-pole oscillation and formed polar patches or foci inH. volcanii. The MinD4 membrane targeting sequence (MTS), homologous to the bacterial MinD MTS, was essential for the oscillation. Surprisingly, MinD4 ATPase domain point-mutations did not block oscillation, but they failed to form pole-patches. Thus, MinD4 fromH. volcaniicombines traits of different bacterial ParA/MinD proteins.
Lack of Adipocyte Purinergic P2Y6Receptor Greatly Improves Whole Body Glucose Homeostasis
Authors: Jain Shanu , Pydi Sai P. , Toti Kiran S. , Robaye Bernard , Idzko Marco , Gavrilova Oksana , Wess Jürgen , Jacobson Kenneth A.
Published: April 2020

Uridine diphosphate (UDP)-activated purinergic receptor P2Y6(P2Y6R) plays a crucial role in controlling energy balance through central mechanisms. However, P2Y6R’s roles in peripheral tissues regulating energy and glucose homeostasis remain unexplored. Here, we report the surprising novel finding that adipocyte-specific deletion of P2Y6R protects mice from diet-induced obesity, improving glucose tolerance and insulin sensitivity with reduced systemic inflammation. These changes were associated with reduced JNK signaling, and enhanced expression and activity of PPARα affecting downstream PGC1α levels leading to beiging of white fat. In contrast, P2Y6R deletion in skeletal muscle reduced glucose uptake resulting in impaired glucose homeostasis. Interestingly, whole body P2Y6R KO mice showed metabolic improvements similar to those observed with mice lacking P2Y6R only in adipocytes. Our findings provide compelling evidence that P2Y6R antagonists may prove useful for the treatment of obesity and type 2 diabetes.
The Effect of Sudanese Smokeless Tobacco (Toombak) using on Oral Microbiota
Authors: Abakar Mudathir Abdelshafea Abdelkareem , Omer Abdalazim Abubaker Ismail , Yousif Albashir Mosab Mustafa
Published: April 2020

Background

Toombak,saffaandsaodare the common local name of Sudanese smokeless tobacco which used by large population in different regions in Sudan. That chemical nature of Toomback includes very high levels of carcinogenic substances, strong alkaline materials and microorganisms. The used of Toombak implying application of the highly addictive product in the mouth many times per day for long times differed from users to other.

Objectives

The objective of this study was to study the effect of Toombak on the oral microbial flora (Microbiota).

Materials and Methods

100 buccal swabs were collected in this study, 50 swabs from Toombak users and 50 swabs from non Toombak users as control group. All the participants were non smokers. The swabs were cultured on Chocolate agar, Blood agar and Sabouraud agar and incubated aerobically for up to 7 days. Then colonial morphology, indirect microscopy and biochemical tests were used to identify the isolated organism.

Results

Toomback shows inhibitory effect on theviridanas streptococciand the baccual swabs collected from toomback users show significant increase in number of mixed growth (P value 0.000/ likelihood ratio 43.24) and colonization of oral cavity withBacillus species(P value 0.000/ likelihood ratio 57.41),Aspergillus species(P value 0.003/ likelihood ratio 10.462) andAspergillus flavus(P value 0.036/ likelihood ratio 4.45).

Conclusion

Toombak using is affecting the quality and quantity of the oral normal flora because it has inhibitory effect onviridians streptococci, leading to rising of new colonizing species such asBacillus speciesandAspergillus specieespecially aflatoxins producingAspergillus flavus. These changes in the microenvironment may affect the immunity and health of the Toombak users and may lead to serious oral and systemic health problems.
Pex11β knockdown decreases peroxisome abundance and reverses the inhibitory effect of palmitate on pancreatic beta-cell function
Authors: Blair Helen R , Tomas Cara , Brown Audrey E , Miwa Satomi , Health Alan , Russell Alison , Ginkel Michael-van , Gunn David , Walker Mark
Published: April 2020

Aims

Reactive oxygen species generated by the peroxisomes and mitochondria contribute to lipotoxicity in pancreatic beta-cells. Through targetedPex11β knockdown and peroxisome depletion, our aim was to investigate the specific contribution of peroxisomes to palmitate mediated pancreatic beta-cell dysfunction.

Methods

MIN6 cells were transfected with probes targeted againstPex11β, a regulator of peroxisome abundance, or with scrambled control probes. Peroxisome abundance was measured by PMP-70 protein expression. 48hrs post transfection, cells were incubated with or without 250μM palmitate for a further 48hrs before measurement of reactive oxygen species, mitochondrial respiratory function, and glucose stimulated insulin secretion.

Results

Pex11β knockdown decreased target gene expression by more than 80% compared with the scrambled control (P<0.001), leading to decreased PMP-70 expression (p<0.01).Pex11β knockdown decreased palmitate mediated generation of reactive oxygen species (P<0.001), but with no effect on mitochondrial respiratory function. At 25mM glucose, palmitate treatment decreased insulin secretion in the control cells (2.54±0.25 vs 7.07±0.83 [mean±SEM] ng/hr/μg protein; P<0.001), with a similar pattern in thePex11β knockdown cells. However, in the presence of palmitate, insulin secretion was significantly higher in thePex11β knockdown versus control cells (4.04±0.46 vs 2.54±0.25 ng/hr/μg protein; p<0.05).

Conclusion

Pex11β knockdown decreased peroxisome abundance, decreased palmitate mediated ROS generation, and reversed the inhibitory effect of palmitate on insulin secretion. These findings highlight a specific and independent role for peroxisomes in pancreatic beta-cell lipotoxicity.
UltraPrep is a scalable, cost-effective, bead-based method for purifying cell free DNA
Authors: Raymond Christopher K. , Raymond Fenella C. , Hill Kay
Published: April 2020

UltraPrep is an open-source, two-step method for purification of cell-free DNA that entails extraction of total DNA followed by size-selective enrichment of the smaller fragments that are characteristic of DNA originating from fragmentation between nucleosome. The advantages of the method are that it can easily accommodate a wide range of sample input volumes, it relies on simple, magnetic bead-based technology, the yields of cfDNA are directly comparable to the most popular methods for cfDNA purification, and it dramatically reduces the cost of cfDNA isolation relative to currently available commercial methods. We provide a framework for physical and molecular quality analysis of purified cfDNA and demonstrate that the cfDNA generated by UltraPrep meets or exceeds the quality metrics of the most commonly used procedure. Our method removes high molecular weight genomic DNA that can interfere with downstream assay results, thereby addressing one of the primary concerns for preanalytical collection of blood samples.
Multi-trait regressor stacking increased genomic prediction accuracy of sorghum grain composition
Authors: Sapkota Sirjan , Boatwright Jon Lucas , Jordan Kathleen , Boyles Richard , Kresovich Stephen
Published: April 2020

Cereal grains, primarily composed of starch, protein, and fat, are major source of staple for human and animal nutrition. Sorghum, a cereal crop, serves as a dietary staple for over half a billion people in the semi-arid tropics of Africa and South Asia. Genomic prediction has enabled plant breeders to estimate breeding values of unobserved genotypes and environments. Therefore, the use of genomic prediction will be extremely valuable for compositional traits for which phenotyping is labor-intensive and destructive for most accurate results. We studied the potential of Bayesian multi-output regressor stacking (BMORS) model in improving prediction performance over single trait single environment (STSE) models using a grain sorghum diversity panel (GSDP) and a biparental recombinant inbred lines (RILs) population. A total of five highly correlated grain composition traits: amylose, fat, gross energy, protein and starch, with genomic heritability ranging from 0.24 to 0.59 in the GSDP and 0.69 to 0.83 in the RILs were studied. Average prediction accuracies from the STSE model were within a range of 0.4 to 0.6 for all traits across both populations except amylose (0.25) in the GSDP. Prediction accuracy for BMORS increased by 41% and 32% on average over STSE in the GSDP and RILs, respectively. Predicting whole environments by training with remaining environments in BMORS yielded higher average prediction accuracy than from STSE model. Our results show regression stacking methods such as BMORS have potential to accurately predict unobserved individuals and environments, and implementation of such models can accelerate genetic gain.
Paxillin Promotes ATP-induced Activation of P2X7 Receptor and NLRP3 Inflammasome
Authors: Wang Wenbiao , Hu Dingwen , Feng Yuqian , Wu Caifeng , Song Yunting , Liu Weiyong , Li Aixin , Wang Yingchong , Chen Keli , Tian Mingfu , Xiao Feng , Zhang Qi , Chen Weijie , Pan Pan , Wan Pin , Liu Yingle , Wu Kailang , Wu Jianguo
Published: April 2020

The stimulation of P2X7 receptor by extracellular ATP leads to activation of NLRP3 inflammasome and release of pro-inflammatory cytokines. Here, we reveal a distinct mechanism by which Paxillin promotes ATP-induced activation of P2X7 receptor and NLRP3 inflammasome. Extracellular ATP induces Paxillin phosphorylation and facilitates Paxillin-NLRP3 interaction. Interestingly, Paxillin enhances NLRP3 deubiquitination and activates NLRP3 inflammasome upon ATP treatment and K+efflux. Moreover, we reveal that UPS13 is a key enzyme for Paxillin-mediated NLRP3 deubiquitination upon ATP treatment. Notably, extracellular ATP promotes Paxillin and NLRP3 migration from cytosol to plasma membrane and facilitates P2X7-Paxillin interaction and Paxillin-NLRP3 association, resulting in the formation of P2X7-Paxillin-NLRP3 complex. Functionally, Paxillin is essential for ATP-induced NLRP3 inflammasome activation in mouse BMDMs and BMDCs as we as in human PBMCs and THP-1-differentiated macrophages. Thus, Paxillin plays key roles in ATP-induced activation of P2X7 receptor and NLRP3 inflammasome by facilitating the formation of the P2X7-Paxillin-NLRP3 complex.
3-Dimensional Organization and Dynamics of the Microsporidian Polar Tube Invasion Machinery
Authors: Jaroenlak Pattana , Cammer Michael , Davydov Alina , Sall Joseph , Usmani Mahrukh , Liang Feng-Xia , Ekiert Damian C. , Bhabha Gira
Published: April 2020

Microsporidia, a divergent group of single-celled eukaryotic parasites, harness a specialized harpoon-like invasion apparatus called the polar tube (PT) to gain entry into host cells. The PT is tightly coiled within the transmissible extracellular spore, and is about 20 times the length of the spore. Once triggered, the PT is rapidly ejected and is thought to penetrate the host cell, acting as a conduit for the transfer of infectious cargo into the host. The organization of this specialized infection apparatus in the spore, how it is deployed, and how the nucleus and other large cargo are transported through the narrow PT are not well understood. Here we use serial block-face scanning electron microscopy to reveal the 3-dimensional architecture of the PT and its relative spatial orientation to other organelles within the spore. Using high-speed optical microscopy, we also capture and quantify the entire PT germination processin vitro. Our results show that the emerging PT experiences very high accelerating forces to reach velocities exceeding 300 μm.s-1, and that firing kinetics differ markedly between species. Live-cell imaging reveals that the nucleus, which is approximately 7 times larger than the diameter of the PT, undergoes extreme deformation to fit through the narrow tube, and moves at speeds comparable to PT extension. Our study sheds new light on the 3-dimensional organization, dynamics, and mechanism of PT extrusion, and shows how infectious cargo moves through the tube to initiate infection.
Who are the multichannel shoppers and how can retailers use them? Evidence from the French apparel industry
Authors: Jo Wooyong , Kim Jikyung (Jeanne) , Choi Jeonghye
Published: April 2020

Purpose

This study aims to identify, within the context of the French fashion industry, the characteristics of multichannel shoppers, that is, consumers who use more than one channel in a single shopping trip. We especially investigate whether consumers' focus on quality versus price affects their multichannel shopping tendency and their flexibilities in their shopping lists (basket flexibility).

Design/methodology/approach

We surveyed a representative sample of 400 French shoppers regarding fashion apparel purchasing. We use a logistic regression framework to measure the probability of a shopper becoming a multichannel shopper based on the key constructs and a battery of control variables.

Findings

The analysis shows that, in fashion buying, shoppers focused on quality and those with high basket flexibility have a higher probability of becoming multichannel shoppers. The probability becomes even greater when a shopper is both quality oriented and has basket flexibility.

Research limitations/implications

We focus on the fashion apparel market for a deeper understanding of multichannel usage of products with both experience and search features. Future research can investigate other industries for higher generalizability.

Practical implications

Our research provides insights into multichannel fashion companies whose managements aim to effectively manage high-value customers who tend to use more channels when shopping. Specifically, an omnichannel marketing strategy should focus on capturing the quality-oriented and highly basket-flexible segment of consumers.

Originality/value

Our study provides evidence that for products having high experiential as well as search features, quality-oriented and highly flexible shoppers engage more in multichannel shopping. Because these characteristics are related to the long-term value of customers, we provide the link between multichannel marketing and firm profitability in the context of the fashion industry.
Successful without profits: personal factors that affect performance in NPOs
Authors: Reinhardt Andreas , Enke Susanne
Published: April 2020

Purpose

Studies on personal characteristics that influence managers' performance in their jobs and their ability to innovate focus mainly on for-profit organizations. We argue that non-profit organizations (NPOs) differ substantially from for-profit organizations in their organizational set-up and processes, so the skills they demand from their managers and employees also differ. We undertake this research to explore the personal factors that could be particularly relevant to managers' performance and innovativeness in the non-profit sector.

Design/methodology/approach

We conduct a qualitative, model-building study to derive the personal factors that influence managers' intention to perform and to innovate and their behavior in that regard. The base of our analysis is 15 interviews with knowledgeable informants who either work in NPOs, provide services to them or perform research about them.

Findings

We derive 14 personal factors that can be aggregated into four categories—experience, virtues and vices, interpersonal skills and management skills—each of which affect NPO managers' individual performance and/or individual innovativeness.

Originality/value

This study adds to existing research on Ajzen's (1985) Theory of Planned Behavior by extending it to the nonprofit context, so it contributes to the literature on individuals' behavioral intentions.
The affective component of ageism needs attention
Authors: Solem Per Erik
Published: April 2020

Purpose

The purpose of this paper is to explore responses of older workers and of managers to the call from the authorities to extend working life.

Design/methodology/approach

Data are from the Norwegian Senior Policy Barometer with interviews with samples of about 750 managers and 1,000 workers each year from 2003. There is no panel data.

Findings

Older workers increasingly prefer to extend their working career. The preferred age for exit has increased from 61 years in 2003 to 66 years in 2018. Managers seem less interested in expanding their older workforce. A majority of managers expressed quite positive conceptions of older workers' performance, but less often they liked to recruit older workers. As an average, managers told that they would hesitate to call in applicants above 58 years of age to job interviews. Age for hesitation is only moderately correlated (r = 0.29) to managers' beliefs about older workers’ performance at work. Thus, the managers' beliefs about older workers’ performance made only a small difference for their willingness to hire older workers.

Research limitations/implications

The results suggest that counteracting stereotypes, prejudice and age discrimination in working life needs a broad approach, including attention to the affective component of ageism. For research, the measurement of the affective component needs consideration and further exploration.

Originality/value

The article brings data from a distinctive Norwegian context and approaches the rarely studied affective component of ageism in working life.
Heat-related productivity loss: benefits derived by working in the shade or work-time shifting
Authors: Morabito Marco , Messeri Alessandro , Crisci Alfonso , Bao Junzhe , Ma Rui , Orlandini Simone , Huang Cunrui , Kjellstrom Tord
Published: April 2020

Purpose

Agricultural workers represent an important part of the population exposed to high heat-related health and productivity risks. This study aims to estimate the heat-related productivity loss (PL) for moderate work activities in sun and shady areas and evaluating the economic cost locally in an Italian farm and generally in the whole province of Florence. Benefits deriving by working in the shade or work-time shifting were provided. Comparisons between PL estimated in Mediterranean (Florence, Italy) and subtropical (Guangzhou, China) areas were also carried out.

Design/methodology/approach

Meteorological data were collected during summers 2017–2018 through a station installed in a farm in the province of Florence and by two World Meteorological Organization (WMO)‐certified meteorological stations located at the Florence and Guangzhou airports. These data were used to calculate the wet-bulb globe temperature and to estimate the hourly PL and the economic cost during the typical working time (from 8 a.m. to 5 p.m.) and by advancing of 1 h and 2 h the working time. Significant differences were calculated through nonparametric tests.

Findings

The hourly PL and the related economic cost significantly decreased (p < 0.05) by working in the shade and by work-time shifting. Higher PL values were observed in Guangzhou than in Florence. The decrease of PL observed by work-time shifting was greater in Florence than in Guangzhou.

Originality/value

Useful information to plan suitable heat-related prevention strategies to counteract the effects of heat in the workplace are provided. These findings are essential to quantify the beneficial effects due to the implementation of specific heat-related adaptation measures to counter the impending effects of climate change.
Genetic analyses of mosaic neurofibromatosis type 1 with giant café‐au‐lait macule, plexiform neurofibroma and multiple melanocytic nevi
Authors: Hida Tokimasa , Idogawa Masashi , Okura Masae , Sugita Shintaro , Sugawara Taro , Sasaki Yasushi , Tokino Takashi , Yamashita Toshiharu , Uhara Hisashi
Published: April 2020

Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second‐hit NF1 aberration results in the formation of café‐au‐lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1‐related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café‐au‐lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25–30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1‐like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.
Population viability analysis of small population: a case study for Asian elephant in China
Authors: HE Changhuan , DU Jiaojiao , ZHU Di , ZHANG Li
Published: April 2020

Small populations are at risk of extinction from deterministic and stochastic factors. Less than 250 Asian elephants (Elephas maximus) remain in China, and are distributed in a few isolated areas; yet, population viability analyses of this endangered population have not been conducted. Here, the current genetic status of the Pu'Er‐Mengyang Asian elephant populations in China was analyzed, and the risk of extinction was predicted over the next 500 years. Factors affecting the viability of this population were determined through simulations. The genetic diversity of the population was very low (mean allele number: 3.1; expected heterozygosity: 0.463), even though a recent population bottleneck was not detected. The effective population size was approximately 24.1 adult elephants. Enough adult breeding individuals exist to maintain population viability. VORTEX simulation model showed that this population would not go extinct in the next 500 years. However, illegal poaching and harvesting could negatively affect population size. A sensitivity analysis showed that the mean stochastic growth rate of the study population is sensitive to sex ratio, number of breeding females, mortality of females of different age classes, carrying capacity, and lethal equivalents. Based on our results, we suggest that action should be taken to alleviate inbreeding and any further loss of genetic diversity, by connecting fragmented elephant habitat or by translocating individual elephants. In addition, human–elephant conflict should be mitigated using various modern approaches, including crop guarding techniques, and by encouraging farmers to switch to crops and income sources not vulnerable to elephant raids.
Prophage encoding toxin/antitoxin system PfiT/PfiA inhibits Pf4 production in Pseudomonas aeruginosa
Authors: Li Yangmei , Liu Xiaoxiao , Tang Kaihao , Wang Weiquan , Guo Yunxue , Wang Xiaoxue
Published: April 2020

Pf prophages are ssDNA filamentous prophages that are prevalent among various Pseudomonas aeruginosa strains. The genomes of Pf prophages contain not only core genes encoding functions involved in phage replication, structure and assembly but also accessory genes. By studying the accessory genes in the Pf4 prophage in P. aeruginosa PAO1, we provided experimental evidence to demonstrate that PA0729 and the upstream ORF Rorf0727 near the right attachment site of Pf4 form a type II toxin/antitoxin (TA) pair. Importantly, we found that the deletion of the toxin gene PA0729 greatly increased Pf4 phage production. We thus suggest the toxin PA0729 be named PfiT for Pf4 inhibition toxin and Rorf0727 be named PfiA for PfiT antitoxin. The PfiT toxin directly binds to PfiA and functions as a corepressor of PfiA for the TA operon. The PfiAT complex exhibited autoregulation by binding to a palindrome (5′‐AATTCN5GTTAA‐3′) overlapping the ‐35 region of the TA operon. The deletion of pfiT disrupted TA autoregulation and activated pfiA expression. Additionally, the deletion of pfiT also activated the expression of the replication initiation factor gene PA0727. Moreover, the Pf4 phage released from the pfiT deletion mutant overcame the immunity provided by the phage repressor Pf4r. Therefore, this study reveals that the TA systems in Pf prophages can regulate phage production and phage immunity, providing new insights into the function of TAs in mobile genetic elements.
Cantharidin‐loaded functional mesoporous titanium peroxide nanoparticles for non‐small cell lung cancer targeted chemotherapy combined with high effective photodynamic therapy
Authors: Zheng Kun , Chen Runze , Sun Yanxue , Tan Zhenquan , Liu Ye , Cheng Xiao , Leng Junke , Guo Zhaoming , Xu Pengcheng
Published: April 2020

Background

Although photodynamic therapy (PDT) has emerged as a potential alternative to conventional chemotherapy, the low reactive oxygen species (ROS) yield of the photosensitizer such as TiO2 nanoparticles has limited its application. In addition, it is difficult to achieve effective tumor treatment with a single tumor therapy.

Methods

We used TiOx nanocomposite (YSA‐PEG‐TiOX) instead of TiO2 as a photosensitizer to solve the problem of insufficient ROS generation in PDT. Benefiting from the desired mesoporous structure of TiOx, Cantharidin (CTD), one of the active components of mylabris, is loaded into TiOx for targeted combination of chemotherapy and PDT. The cellular uptake in human non‐small cell lung carcinoma cell line (A549) and human normal breast cell line (MCF 10A) was evaluated by confocal microscopy. in vitro cytotoxicity was evaluated using Cell Counting Kit‐8 assay. The ROS was detected via a chemical probe DCFH‐DA and the photodynamic treatment effect of YSA‐PEG‐TiOx was further evaluated by a living‐dead staining. The cell apoptosis was detected by the flow cytometry.

Results

Our findings showed that the modification of YSA peptide improved the cytotoxicity of YSA‐PEG‐TiOX/CTD to EphA2 overexpressing A549 non‐small cell lung cancer (NSCLC) than non‐YSA modified counterparts. In addition, TiOx generated adequate ROS under X‐ray irradiation to further kill cancer cells. Flow analysis results also proved the superiority of this combined treatment.

Conclusions

YSA‐PEG‐TiOX nanoparticles could significantly increase ROS production under X‐ray exposure and provide a new drug delivery nanocarrier for CTD in combination with PDT to achieve effective NSCLC treatment.
Rapid development and rupture of a pulmonary cyst in the early postoperative period after pulmonary resection: A case report
Authors: Kawamoto Nobutaka , Okita Riki , Hayashi Masataro , Furukawa Masashi , Inokawa Hidetoshi , Okabe Kazunori
Published: April 2020

Air leakage is a common complication after pulmonary resection, which is usually caused by direct lung damage during surgery. Herein, we describe a case in which a pulmonary cyst developed rapidly in the right lower lobe and ruptured 10 days after right upper lobectomy. A 49‐year‐old man, who was a heavy smoker, underwent thoracoscopic right upper lobectomy for primary lung cancer. No air leakage was observed postoperatively, and the chest drain tube was removed on postoperative day 1. Although his postoperative course was uneventful for more than a week, extensive subcutaneous emphysema developed unexpectedly on postoperative day 10. Computed tomography (CT) scan revealed a large pulmonary cyst in the right lower lobe that was not present before the right upper lobectomy. Surgery was performed on postoperative day 13, and it revealed a large thick‐walled pulmonary cyst in the right lower lobe. The cyst was filled with blood clots, and air leaks were observed inside it, suggesting that the dissection of the pulmonary parenchyma caused its development. The cyst wall was sutured together with the pulmonary parenchyma, and no air leakage was subsequently observed.

Key points

Significant findings of the study

In patients with fragile pulmonary tissue, the pulmonary parenchyma may become dissociated after pulmonary resection and induce rapid development of a pulmonary cyst.

Risk factors for pulmonary cyst development include upper lobectomy and emphysema. Pulmonary cysts are often formed in the lower lobe.

What this study adds

In patients with pulmonary emphysema post‐upper lobectomy, the fragility of the pulmonary parenchyma and hyperinflation of the remaining lung may cause dissection of the pulmonary parenchyma, resulting in massive air leakage.
Persistent Hyperactivation of Endothelial Cells in Patients with Alcoholic Hepatitis
Authors: Xia Ying , Yang Jing , Sanyal Arun J. , Shah Vijay H. , Chalasani Naga P. , Yu Qigui , Zheng Xiaoqun , Li Wei
Published: April 2020

Background

Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up‐regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM‐1, VCAM‐1, and VEGF‐A) and the effect of alcohol abstinence on the reversal of these abnormalities in heavy drinkers with and without AH.

Methods

ELISA and multiplex immunoassays were used to measure soluble EC activation markers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6‐month follow‐up, and 18 AH patients and 25 HDC at 12‐month follow‐up.

Results

At baseline, the 4 soluble markers were significantly up‐regulated in AH patients compared with HDC and HC, whereas only sVCAM‐1 was elevated in HDC relative to HC. At follow‐ups, plasma levels of CD146, VCAM‐1, and VEGF‐A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several soluble inflammatory factors.

Conclusions

The levels of soluble CD146, ICAM‐1, VCAM‐1, and VEGF‐A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities.
Electroretinography and retinal microvascular changes in type 2 diabetes
Authors: Kim Mirinae , Kim Rae‐Young , Park Wookyung , Park Young‐Gun , Kim In‐Beom , Park Young‐Hoon
Published: April 2020

Purpose

To assess whether functional (electrophysiological) parameters are related to changes in the structural (microvascular) parameters in diabetic retina.

Methods

This prospective cohort study included 380 eyes of patients with diabetes mellitus (DM) and 160 eyes of healthy controls. We analysed the electroretinogram (ERG) parameters and vascular parameters acquired from optical coherence tomography (OCT) angiography according to the diabetic retinopathy (DR) severity from early to late stages of DR.

Results

After exclusion, 366 eyes of diabetes and 157 eyes of controls were included in the analysis. The mean age at enrolment was 65.4 ± 7.8 years, and 177 (33.84%) were male. The amplitude and implicit time of the rod and cone and combined response ERG b‐wave were significantly reduced and prolonged in the eyes of patients with DM, compared to the controls. There was a positive correlation between the amplitude and vessel density (VD) of the superficial plexus and a negative correlation between the implicit time and superficial VD in the scotopic and combined response b‐wave. Interestingly, there was no correlation between electrophysiological parameters and deep VD. These correlations between electrophysiological parameters and vascular parameters were not significant in the non‐diabetic, healthy control group.

Conclusions

Functional and structural impairments precede the clinical manifestation of DR. We also found that these neural impairments, evaluated by ERG, were correlated with superficial VD. However, this correlation was absent in the healthy and early DR groups. These findings carefully suggest that neuronal dysfunction is linked to vascular dysfunction in type 2 diabetes.
Ribosomal protein S6 promotes stem‐like characters in glioma cells
Authors: Shirakawa Yuki , Hide Takuichiro , Yamaoka Michiko , Ito Yuki , Ito Naofumi , Ohta Kunimasa , Shinojima Naoki , Mukasa Akitake , Saito Hideyuki , Jono Hirofumi
Published: April 2020

Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans‐differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high‐grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA‐mediated RPS6 knock‐down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC‐predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence.