bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear: Introduction to special issue
Authors: Hill Annette , Mortensen Mette , Hermes Joke
Published: September 2021

Fear needs dealing with. Fear demands to be abated, countered or turned into something else, contributing and curtailing how we ‘do’ being human beings. This special issue of the European Journal of Cultural Studies addresses fear within media and popular culture, adopting a cultural studies approach to fear in a variety of socio-cultural and political contexts. A cultural studies approach allows us to enhance the horizon of understanding cultural practices, mediation and the subjective experience of fear as something we need to work through, in a process of recognition and shock, action and reaction, understanding and reflection. This focus on ‘working through fear’ offers new insights into the intensely subjective aspects of fear as it is creatively explored in representations within drama and documentary, photography and art, and in user-generated content, memes and political satire, and as it is embodied and experienced by people in the context of their realities. In addition, it shows how fear generates energy, anxiety and even desire. Rather than offering a generalizing account, this issue seeks to address fear in specific contexts, localities and from specific roles and perspectives.
A comparative study of univariate models for container throughput forecasting of major ports in Asia
Authors: Huang Juan , Chu Ching-Wu , Hsu Hsiu-Li
Published: September 2021

This study aims to make comparisons on different univariate forecasting methods and provides a more accurate short-term forecasting model on the container throughput for rendering a reference to relevant authorities. We collected monthly data regarding container throughput volumes for three major ports in Asia, Shanghai, Singapore, and Busan Ports. Six different univariate methods, including the grey forecasting model, the hybrid grey forecasting model, the multiplicative decomposition model, the trigonometric regression model, the regression model with seasonal dummy variables, and the seasonal autoregressive integrated moving average (SARIMA) model, were used. We found that the hybrid grey forecasting model outperforms the other univariate models. This study’s findings can provide a more accurate short-term forecasting model for container throughput to create a reference for port authorities.
Protecting nurse survey participants: Ethical considerations for conducting survey research among nurses
Authors: Campbell Caitlin M , Taylor-Clark Tanekkia , A Loan Lori
Published: September 2021

The nurse perspective is critical in survey research investigating various aspects of healthcare services, staff, and patient outcomes. Researchers are responsible for ensuring that survey research utilizing survey questionnaires employs research methodological strategies that are aligned with the ethical principles of beneficence, respect for persons, and justice. The purpose of this paper is to discuss best practices to facilitate high-quality survey data collection for nurse survey participants. Recommendations are based on the fundamental ethical principles described in the Belmont Report, an overview of evidence published in the current literature, and the application of practical knowledge. Literature searches conducted in PubMed resulted in the inclusion of over 50 articles from a wide range of disciplines. The results include actionable methods for researchers to consider and follow when conducting survey research utilizing nurse participants. This article serves as a resource to guide researchers through ethically responsible design, implementation, and reporting of nurse survey research.
The effects of aircraft use and available repair spares on aircraft sortie generation: a long-duration logistical wargaming simulation tool
Authors: Choo Nathaniel , Ahner Darryl , Champagne Lance
Published: September 2021

Long-duration logistical wargames within the Air domain are complex and highly dynamic events that are driven by aircraft availability. In order to gain insight into the impact of aircraft use, this research developed a simulation tool that uses a stepwise approach for adjudication and provides the user many capabilities including, but not limited to, the ability to have multiple bases and types of aircraft. Daily aircraft availability and missions accomplished are two critical metrics of interest. Within the simulation, the user has the ability to control types of part failures, control parts availability, control maintenance capabilities, and control number of mission scheduled. Finally, the user can account for the possibility of attrition along with the effects of numerous major events present in real-life scenarios. This tool is validated through application of a space covering design along with regression modeling and shows that the tool is well-behaved, functions as expected, and can quickly provide meaningful insights into operational scenarios.
Pioglitazone combined with atorvastatin promotes plaque stabilization in a rabbit model
Authors: Zhang Xuehui , Chen Xue , Liang Zhe , Nie Maoxiao , Yan Yunfeng , Zhao Quanming
Published: September 2021

Objective

It is not yet clear whether plaque inflammation and cardiovascular events are reduced further when pioglitazone and atorvastatin are combined. Our study aimed to determine whether pioglitazone combined with atorvastatin can restrain the progression of atherosclerosis and promote plaque stabilization in a rabbit model

Method and Result

Thirty rabbits were randomly divided into an atherosclerosis group, an atorvastatin group, and an atorvastatin plus pioglitazone group. The atherosclerosis model was induced using balloon injury and feeding a high-fat diet. Plasma samples were then used to analyze glucose, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hs-CRP), and matrix metalloproteinase-9 (MMP-9). The area percentage of atherosclerotic plaques was analyzed by hematoxylin-eosin staining. The relative reductions in TG and LDL-C and the increase in HDL-C levels were significantly greater in the combination therapy group than in the atorvastatin monotherapy group (TG: −33.60 ± 7.17% vs −24.16 ± 8.04%, p < 0.001; LDL-C: −42.89 ± 1.63% vs −37.13 ± 1.35%, p < 0.001; and HDL-C: 25.18 ± 5.53% vs 10.43 ± 6.31%, p < 0.001). The relative reductions in hs-CRP and MMP-9 levels were significantly greater in the combination therapy group than in the atorvastatin monotherapy group (−69.38 ± 1.06% vs-53.73 ± 1.92%, p < 0.001; −32.77 ± 2.49% vs −13.36 ± 1.66%, p < 0.001). The area percentage of atherosclerotic plaques was significantly smaller in the atorvastatin group (47.75%, p < 0.05) and in the atorvastatin plus pioglitazone group (22.57%, p < 0.05) than in the atherosclerosis group (84.08%, p < 0.05)

Conclusion

We can thus conclude that the combination treatment of atorvastatin and pioglitazone provided additive benefits on inflammatory parameters and lipid metabolism. Pioglitazone combined with atorvastatin can further restrain the progression of atherosclerosis and promote plaque stabilization in a rabbit model.
Violence, crime dystopia and the dialectics of (dis)order inThe Purgefilms
Authors: Alexandrescu Liviu
Published: September 2021

Crime dystopia is the cultural site where some of the most gripping fears around the failure to order, civilise and make life secure are expressed. In The Purge film franchise, crime becomes legal in America for a night each year, when violence and destructive impulses are freely discharged and actively encouraged by the US government. This article proposes a critical discussion of some of the criminological themes in the films, reading the institutionalised carnage of Purge night as a metaphor for the systemic violence of the market and further on for liberal governance as a philosophy of war, scarred by the horror of hidden monsters. It then argues that dystopian aesthetics can obscure the failures and antagonisms of the social order in the present, as well as punctuate anti-utopian fears of the future.
Examining the geographic distribution of six chronic disease risk factors for severe COVID-19: Veteran–nonveteran differences
Authors: McDaniel Michelle , McDaniel Justin T
Published: September 2021

Objectives

We aimed to better understand where the prevalence of risk factors for severe COVID-19 occur, especially among veterans and nonveterans – populations that are given the opportunity to seek healthcare from separate entities.

Methods

In this cross-sectional study, we use data from the SMART Behavioral Risk Factor Surveillance System to estimate the prevalence (i.e., survey-weighted %) of six risk factors for severe COVID-19 (i.e., chronic obstructive pulmonary disorder [COPD], asthma, diabetes, obesity, cardiovascular disease, and kidney disease) for veterans and nonveterans at the national level, in 155 metropolitan/micropolitan statistical areas, and in Veteran Integrated Service Networks (veterans only). We examine differences in these outcomes among veterans and between geographic areas using chi-square analysis or multivariable logistic regression.

Results

In the national aggregate, veterans exhibited higher prevalence rates of COPD, diabetes, cardiovascular disease, and kidney disease than nonveterans, but not asthma and obesity. However, we show significant variation in the prevalence of risk factors for severe COVID-19 among veterans by geographic location.

Discussion

This study provides a dataset that can be used by healthcare providers in order to prioritize prevention programming for veterans who may be at higher risk for COVID-19 due to their increased risk for certain chronic diseases.
Notification alert! Effects of auditory text alerts on attention and heart rate variability across three developmental periods
Authors: Whiting Wythe L , Murdock Karla Klein
Published: September 2021

In a modern world saturated with cellphone-related stimuli, surprisingly little is known about their psychological effects. A small number of previous studies have found global distracting effects of cellphone rings on cognitive performance in undergraduate students. However, moment-to-moment reactions to cellphone sounds have not been investigated, nor have physiological changes that might accompany the cognitive effects. Developmental variations also remain unexamined. Thus, two experiments were conducted to examine the effects of cellphone notification sounds on cognitive performance (i.e., reaction time and accuracy on math problems) and heart rate variability in three age groups: adolescents (mean age: 15 years); young adults (mean age: 20 years); and mid-life adults (mean age: 48 years). Effects were most pronounced in the adolescent group, whose math problem accuracy and reaction time was compromised in response to notification sounds. These compromises were accompanied by increases in heart rate variability.
Basic science approaches to common hand surgery problems
Authors: Wong Jason , Murphy Matthew , Wu Ya Fang , Murphy Ralph , Frueh Florian S. , Farnebo Simon
Published: September 2021

The field of hand surgery is constantly evolving to meet challenges of populations with increasing age and higher demands for active living. While our surgical care has improved over the last decades, it seems that future major improvement in outcomes of clinical treatment will come through advances in biologics and the translation of major discoveries in basic science. This article aims to provide an update on where basic science solutions may answer some of the most critical issues in hand surgery, with a focus on augmentation of tissue repair.
Clinical factors and mortality rates for non-traumatic upper extremity amputations
Authors: Ting Yong-Zheng Jonathan , Tan An-Sen , Lai Chi-Peng Timothy , Satku Mala
Published: September 2021

Non-traumatic upper extremity amputations are an increasing concern with the rising prevalence of diabetes mellitus. To ascertain the risk factors and mortality rates for these amputations, the demographic information, amputation history, comorbidities and clinical outcomes of 140 patients who underwent non-traumatic upper extremity amputations between 1 January 2004 and 31 October 2017 were studied. Correlations were assessed using Cochran-Armitage chi-squared tests, odds ratios and multivariate binomial logistic regression as appropriate. Diabetes mellitus, coronary artery disease, end-stage renal failure, peripheral arterial disease and prior lower extremity amputation were significant risk factors for multiple upper extremity amputations. One-year, 2-year and 5-year mortality rates were 12%, 15% and 38%, respectively, following first upper extremity amputation. The risk factors for upper extremity amputations correspond with those for lower extremity amputations, comprising mainly diabetes mellitus and its related comorbidities. The mortality rates for non-traumatic upper extremity amputations highlight their significant burden on patients.

Level of evidence: III
Genetic and Environmental Factors of Non-Ability-Based Confidence
Authors: Vogt Randi L. , Zheng Anqing , Briley Daniel A. , Malanchini Margherita , Harden K. Paige , Tucker-Drob Elliot M.
Published: September 2021

Non-ability-based confidence is confidence in one’s ability that is not calibrated to actual ability. Here, we examine what psychological factors are associated with possessing more or less confidence relative to one’s ability and to what extent genetic and environmental processes contribute to these links. Using data from the Texas Twin Project ( N = 1,588 participants, aged 7–15 years), we apply a latent variable residual approach to calculate non-ability-based confidence as self-rated confidence net of ability on standardized cognitive tests. Non-ability-based confidence was modestly heritable (9%–28%) and strongly positively correlated with the need for cognition, mastery goal orientation, grit, openness, and emotional stability. These correlations were partly mediated by genetic factors (57% of the association on average). This widespread pattern of associations between non-ability-based confidence and several other measures of thinking, feeling, and acting suggest that non-ability-based confidence can be conceptualized as a personality attribute.
The Two Minds of Non-Work-Related Computing in the Workplace
Authors: Park Sang Cheol , Tserendulam Munkh-Erdene , Ryoo Sung Yul
Published: September 2021

As information technology (IT) advances and grows in its capabilities, employees are willing to find even more novel ways to fulfill non-work purposes while at work. Non-work-related computing (NWRC), defined as employees’ non-sanctioned personal use of the IT resources in their workplace, has attracted a fair amount of attention. In order to understand why NWRC behavior often occurs, this study adopted a dual approach considering two aspects of human nature: automatic and reflective decision-making systems. Drawing on dual thinking processes, our study aims to examine the relationships among the following: habit as a trigger of automatic thinking, neutralization as a trigger of reflective thinking, and employees’ NWRC behavior in the workplace. Our model posits that employees’ NWRC is influenced by both habit and neutralization. Survey data collected from 176 employees of several banks in Mongolia were used to test our model by using partial least squares analysis. This study found that both habit and neutralization have significant impacts on NWRC. By conducting mediated regression techniques, we also found that neutralization partially mediates the relationship between habit/neutralization and NWRC. In addition to identifying the mediating role of neutralization, the results imply that it is important to prevent NWRC from becoming habitual and to make employees internalize the importance of compliance with internet use policy.
Correlation of Femoral Trochlear Dysplasia With Anterior Cruciate Ligament Injury in Skeletally Immature Patients
Authors: Kwak Yoon Hae , Nam Ji-Hoon , Koh Yong-Gon , Kang Kyoung-Tak
Published: September 2021

Background:

Reports of anterior cruciate ligament (ACL) injury in patients with skeletal immaturity have been increasing. Variations in knee joint anatomy have been linked to ACL injury risk factors.

Purpose:

To identify associations between ACL injury, patella alta, and femoral trochlear dysplasia in patients with skeletal immaturity by using magnetic resonance imaging (MRI).

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

This retrospective study included 231 patients with skeletal immaturity—116 with acute complete noncontact ACL injury and 115 without ACL injury (controls)—who underwent knee MRI. Cases of femoral trochlear dysplasia were divided into 4 types according to the Dejour classification scheme. Patellar height and patellar tendon length were measured via sagittal MRI, and the Insall-Salvati ratio (ISR) was calculated.

Results:

In the ACL injury group, 56 (48.3%) knees exhibited trochlear dysplasia, including 51 (91.1%) that were Dejour type A; and in the control group, 12 (10.4%) knees exhibited trochlear dysplasia, 12 (100%) Dejour type A. The prevalence of femoral trochlear dysplasia was significantly higher in the ACL injury group than in the control group ( P < .001). The ISR was not significantly different between the ACL injury and control groups (0.9 ± 0.2 vs 1 ± 0.2 mm; P = .16). The correlation between ISR >1.2 and presence of ACL injury was not significant.

Conclusion:

Femoral trochlear dysplasia was associated with ACL injury in patients with skeletal immaturity. In particular, Dejour type A femoral trochlear dysplasia was correlated with ACL injury patients with skeletal immaturity. Also, the possibility of ACL damage exists in patients with skeletal immaturity and femoral trochlear dysplasia.
Student–Teacher Gender Matching and Academic Achievement
Authors: Hwang NaYoung , Fitzpatrick Brian
Published: September 2021

Scholars have examined the effects of same-gender teachers on student achievement, but the findings are mixed. In this study, we use 7 years of administrative data from students in elementary and middle schools (i.e., Grades 3 through 8) in Indiana to test links between gender matching and student achievement. We find that female teachers are better at increasing both male and female students’ achievement than their male counterparts in elementary and middle schools. The positive effects of having female math teachers are particularly large for female students’ math achievement, but we do not find evidence for a positive gender matching effect in English language arts. In addition, contrary to popular speculation, boys do not exhibit higher academic achievement when they are assigned to male teachers. Our findings suggest that the effects of teacher gender on student learning vary by subject and gender, but the effect sizes are small.
Determinants of Dual Enrollment Access: A National Examination of Institutional Context and State Policies
Authors: Spencer George , Maldonado Mónica
Published: September 2021

Despite considerable growth in rates of participation in recent years, concerns remain about disparities in access to dual enrollment programs. On one hand, there are questions regarding who has access, which students are most disadvantaged, and which schools fail to offer the opportunity at all? On the other hand, there has been little clarity about what helps to improve access—in particular, what is the role of state policies in this effort? Using nationally representative data sources, this study uses a multilevel approach to understand how dual enrollment participation varies at the level of states, schools, and students. The findings reveal that policy mandates are among the strongest predictors of dual enrollment participation. Furthermore, schools serving greater proportions of racially minoritized students are the least likely to offer dual enrollment, but within schools, students from lower socioeconomic backgrounds have a lower probability of participating relative to their more affluent peers.
Properties of Staphylococcus lugdunensis in Children
Authors: Ochi Fumihiro , Tauchi Hisamichi , Kagajo Mari , Murakami Shinobu , Miyamoto Hitoshi , Hamada Junpei , Eguchi-Ishimae Minenori , Eguchi Mariko
Published: September 2021

Background. Staphylococcus lugdunensis is one of the clinically important coagulase-negative staphylococci. The purpose of this study was to elucidate the microbiological features of S. lugdunensis in hospitalized children. Methods. From January 2012 to December 2019, all isolates were retrospectively screened for S. lugdunensis. Results. Twenty-five children were eligible for study. Nineteen and six children were classified into a critical care unit group (Group A) and a general medical ward group (Group B), respectively. The prevalence of methicillin-resistant S. lugdunensis was significantly higher in Group A than in Group B (68.4% vs 0%; P < .01). Eleven children (44%) had S. lugdunensis infections, while the remaining children were colonized. Six of the 11 infected children (55%) had healthcare-associated infections. Moreover, 3 isolates exhibited the methicillin resistance. Conclusions. The bacteriological characteristics of S. lugdunensis differ depending on patient background. Selection of antibiotic treatment should in part rely on patient background data.
Eye-tunes: role of music in ophthalmology and vision sciences
Authors: Muralidharan Shruti , Ichhpujani Parul , Bhartiya Shibal , Singh Rohan Bir
Published: September 2021

Although the healing effect of music has been recognized since time immemorial, there has been a renewed interest in its use in modern medicine. This can be attributed to the increasing focus on holistic healing and on the subjective and objective aspects of well-being. In ophthalmology, this has ranged from using music for patients undergoing diagnostic procedures and surgery, as well as for doctors and the operation theatre staff during surgical procedures. Music has proven to be a potent nonpharmacological sedative and anxiolytic, allaying both the pain and stress of surgery. This review aims to explore the available evidence about the role of music as an adjunct for diagnostic and surgical procedures in current ophthalmic practices.
Dynamic updating of post-earthquake damage and functional restoration forecasts of water distribution systems using Bayesian inferencing
Authors: Tomar Agam , Burton Henry V , Mosleh Ali
Published: September 2021

A framework for dynamically updating post-earthquake functional recovery forecasts is presented to reduce the epistemic uncertainty in the predictive model. A Bayesian Network (BN) model is used to provide estimates of the total recovery time, and a process-based discrete event simulation (PBDES) model generates forecasts of the complete recovery trajectory. Both models rely on component damage and duration-based input parameters that are dynamically updated using Bayes’ theorem, as information becomes available throughout the recovery process. The effectiveness of the proposed framework is demonstrated through an application to the pipe network of the City of Napa water distribution system. More specifically, pipe damage and repair data from the 2014 earthquake are used as a point of comparison for the dynamic forecasts. It is shown that, over time, the mean value of the total recovery duration generated by the BN-based model converges to the observed value and the dispersion is reduced. Also, despite a crude initial estimate, the median trajectory generated by the PBDES model provides a reasonable approximation of the observed recovery within 30 days following the earthquake. The proposed framework can be used by emergency managers to investigate the efficacy of post-event mitigation measures (e.g. crew allocation, resource prioritization) utilizing the most current data and knowledge.
Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study
Authors: Ceccato Adrian , Dominedò Cristina , Ferrer Miquel , Martin-Loeches Ignacio , Barbeta Enric , Gabarrús Albert , Cillóniz Catia , Ranzani Otavio T. , De Pascale Gennaro , Nogas Stefano , Di Giannatale Pierluigi , Antonelli Massimo , Torres Antoni
Published: September 2021

Background

Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes.

Methods

We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens.

Results

157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25–9.40),Staphylococcus aureusisolation at VAP diagnosis (OR 2.87, 95% CI 1.06–7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48–0.95, per +1°C) to be associated with superinfection.

Conclusions

Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.
Ex vivodelivery of regulatory T-cells for control of alloimmune priming in the donor lung
Authors: Miyamoto Ei , Takahagi Akihiro , Ohsumi Akihiro , Martinu Tereza , Hwang David , Boonstra Kristen M. , Joe Betty , Umana Juan Mauricio , Bei Ke F. , Vosoughi Daniel , Liu Mingyao , Cypel Marcelo , Keshavjee Shaf , Juvet Stephen C.
Published: September 2021

Background

Survival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T-cells (Tregs) are being studied as a cellular therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesised thatin vitro-expanded recipient-derived Tregs can be delivered to donor lungs prior to LTxvia ex vivolung perfusion (EVLP), maintaining their immunomodulatory ability.

Methods

In a rat model, Wistar Kyoto (WKy) CD4+CD25highTregs were expandedin vitroprior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localisation and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127lowTregs were thawed and injected into discarded human lungs during EVLP.

Results

Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet-to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3 days post-transplant where they reduced activation of intra-graft effector CD4+T-cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+and CD15s+).

Conclusions

Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post-transplant. Our organ-directed approach has potential for clinical translation.
Anti-IL5 mepolizumab minimally influences residual blood eosinophils in severe asthma
Authors: Van Hulst Glenn , Jorssen Joseph , Jacobs Nathalie , Henket Monique , Louis Renaud , Schleich Florence , Bureau Fabrice , Desmet Christophe J.
Published: September 2021

Neutralising antibodies against the cytokine interleukin (IL)5 have become widely used for the control of severe eosinophilic asthma. Remarkably, patients receiving neutralising anti-IL5 biological therapies retain a very stable population of residual blood eosinophils. Whether these residual eosinophils are endowed with particular biological activity has not yet been studied, but is of importance in predicting potential long-term effects of IL5 neutralisation in patients. To tackle the effect of IL5 depletion on residual eosinophils, we used a comparative RNA-sequencing approach and compared the gene expression programme of eosinophils arising in IL5-depleted or IL5-replete human or murine hosts, at steady-statein vivoand followingin vitrostimulation with the eosinophil-activating alarmin IL33. We compared blood eosinophils from patients with severe allergic eosinophilic asthma treated with anti-IL5 mepolizumab therapy to those of healthy controls and matched asthma patients receiving anti-IgE omalizumab therapy. We made similar comparisons on bone marrow eosinophils from mice genetically deficient or not for IL5. We report that restriction of IL5 availability did not elicit any detectable transcriptional response in steady-state residual eosinophils in mepolizumab-treated patients or IL5-deficient mice, and influenced only a handful of genes in their response to IL33. Together, these results support the notion that treatment with IL5 neutralising antibodies spares a pool of circulating residual eosinophils largely resembling those of healthy individuals.
Myeloid-cell-specific deletion of inducible nitric oxide synthase protects against smoke-induced pulmonary hypertension in mice
Authors: Gredic Marija , Wu Cheng-Yu , Hadzic Stefan , Pak Oleg , Savai Rajkumar , Kojonazarov Baktybek , Doswada Siddartha , Weiss Astrid , Weigert Andreas , Guenther Andreas , Brandes Ralf P. , Schermuly Ralph T. , Grimminger Friedrich , Seeger Werner , Sommer Natascha , Kraut Simone , Weissmann Norbert
Published: September 2021

Background

Pulmonary hypertension (PH) is a common complication of COPD, associated with increased mortality and morbidity. Intriguingly, pulmonary vascular alterations have been suggested to drive emphysema development. Previously, we identified inducible nitric oxide synthase (iNOS) as an essential enzyme for development and reversal of smoke-induced PH and emphysema, and showed that iNOS expression in bone-marrow-derived cells drives pulmonary vascular remodelling, but not parenchymal destruction. In this study, we aimed to identify the iNOS-expressing cell type driving smoke-induced PH and to decipher pro-proliferative pathways involved.

Methods

To address this question we used 1) myeloid-cell-specific iNOS knockout mice in chronic smoke exposure and 2) co-cultures of macrophages and pulmonary artery smooth muscle cells (PASMCs) to decipher underlying signalling pathways.

Results

Myeloid-cell-specific iNOS knockout prevented smoke-induced PH but not emphysema in mice. Moreover, iNOS deletion in myeloid cells ameliorated the increase in expression of CD206, a marker of M2 polarisation, on interstitial macrophages. Importantly, the observed effects on lung macrophages were hypoxia-independent, as these mice developed hypoxia-induced PH.In vitro, smoke-induced PASMC proliferation in co-cultures with M2-polarised macrophages could be abolished by iNOS deletion in phagocytic cells, as well as by extracellular signal-regulated kinase inhibition in PASMCs. Crucially, CD206-positive and iNOS-positive macrophages accumulated in proximity of remodelled vessels in the lungs of COPD patients, as shown by immunohistochemistry.

Conclusion

In summary, our results demonstrate that iNOS deletion in myeloid cells confers protection against PH in smoke-exposed mice and provide evidence for an iNOS-dependent communication between M2-like macrophages and PASMCs in underlying pulmonary vascular remodelling.
Lifting dyspnoea invisibility: COVID-19 face masks, the experience of breathing discomfort, and improved lung health perception – a French nationwide survey
Authors: Serresse Laure , Simon-Tillaux Noémie , Decavèle Maxens , Gay Frederick , Nion Nathalie , Lavault Sophie , Guerder Antoine , Châtelet Antoine , Dabi Frédéric , Demoule Alexandre , Morélot-Panzini Capucine , Moricot Caroline , Similowski Thomas
Published: September 2021

Question addressed

In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health.

Methods

General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered “no” to “treated for a chronic respiratory disease” (“respiratory healthy”), and 152 answered “yes” (“respiratory disease”). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family+). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision.

Results

Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). “Air hunger” was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+(OR 1.85, 95% CI 1.16–2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73–7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25–0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients’ experiences.

Answer to the question

Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions.
Impact of fan therapy during exercise on breathlessness and recovery time in patients with COPD: a pilot randomised controlled crossover trial
Authors: Long Alex , Cartwright Martin , Reilly Charles C.
Published: September 2021

Background

Patients with COPD reduce physical activity to avoid the onset of breathlessness. Fan therapy can reduce breathlessness at rest, but the efficacy of fan therapy during exercise remains unknown in this population. The aim of the present study was to investigate 1) the effect of fan therapy on exercise-induced breathlessness and post-exercise recovery time in patients with COPD and 2) the acceptability of fan therapy during exercise; and 3) to assess the reproducibility of any observed improvements in outcome measures.

Methods

A pilot single-centre, randomised, controlled, crossover open (nonmasked) trial (clinicaltrials.govNCT03137524) of fan therapyversusno fan therapy during 6-min walk test (6MWT) in patients with COPD and a modified Medical Research Council (mMRC) dyspnoea score ≥2. Breathlessness intensity was quantified before and on termination of the 6MWT, using the numerical rating scale (NRS) (0–10). Post-exertional recovery time was measured, defined as the time taken to return to baseline NRS breathlessness score. Oxygen saturation and heart rate were measure pre- and post-6MWT.

Results

14 patients with COPD completed the trial per protocol (four male, 10 female; median (interquartile range (IQR)) age 66.50 (60.75 to 73.50) years); mMRC dyspnoea 3 (2 to 3)). Fan therapy resulted in lower exercise-induced breathlessness (ΔNRS; Δ modified Borg scale) (within-individual differences in medians (WIDiM) −1.00, IQR −2.00 to −0.50; p<0.01; WIDiM −0.25, IQR −2.00 to 0.00; p=0.02), greater distance walked (metres) during the 6MWT (WIDiM 21.25, IQR 12.75 to 31.88; p<0.01), and improved post-exertional breathlessness (NRS) recovery time (WIDiM −10.00, IQR −78.75 to 50.00; p<0.01). Fan therapy was deemed to be acceptable by 92% of participants.

Conclusion

Fan therapy was acceptable and provided symptomatic relief to patients with COPD during exercise. These data will inform larger pilot studies and efficacy studies of fan therapy during exercise.
Suppression of epithelial abnormalities by nintedanib in induced-rheumatoid arthritis-associated interstitial lung disease mouse model
Authors: Miura Yoko , Ohkubo Hirotsugu , Niimi Akio , Kanazawa Satoshi
Published: September 2021

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is relevant for the prognosis in patients with RA. Nintedanib, which inhibits both receptor and non-receptor type tyrosine kinases, is an antifibrotic drug for the treatment of progressive fibrosing ILDs, such as idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease. Little is known about the effects of nintedanib on RA-ILD. We examined the characteristics of a novel induced RA-ILD (iRA-ILD) mouse model and the effects of nintedanib on the model.

D1CC×D1BC mice are highly susceptible to arthritogenic antigens, such as bovine type II collagen, resulting in severe inflammatory arthritis. ILD develops after joint inflammation is alleviated. Serum surfactant protein D levels were monitored as an ILD marker. Nintedanib was orally administered to iRA-ILD mice for 2 months.

The iRA-ILD model showed similar symptoms to those in patients with RA-ILD. The histopathological features of pulmonary disorder resembled nonspecific interstitial pneumonia, but with metaplastic epithelium. Histopathological analysis revealed that in addition to reducing fibrosis, nintedanib suppressed M2 macrophage polarisation and hyperplasia of Type 2 alveolar epithelial cells. The metaplastic epithelium acquired invasiveness because of the expression of E-cadherin, MMP7,Tgf-β,Col1a1,Padi2andPadi4. Moreover, citrullinated peptides were detected in these invasive epithelial cells as well as in the bronchiolar epithelium. Administration of nintedanib reduced the expression of Pad4 and citrullinated peptides and eliminated invasive epithelial cells.

The broad inhibitory effects of nintedanib on tyrosine kinases may contribute to the overall improvement in RA-ILD, including epithelial abnormalities associated with progressive lung fibrosis.
Sexual selection on population-level mating opportunities drives morph ratios in a fig wasp with extreme male dimorphism
Authors: Cook James M.
Published: September 2021

Background

Alternative mating tactics are widespread in animals and associated with extreme morphological polymorphism in some insects. Some fig wasps have both highly modified wingless males and dispersing winged males. Wingless males mate inside figs before females disperse, while winged males mate elsewhere after dispersal. Hamilton proposed a model for this system with morphs determined by alternative alleles. This has an equilibrium where the proportion of winged males equals the proportion of females dispersing unmated; i.e. the proportion of matings that they obtain. Previously, we have shown qualitative support for this prediction across nine wing-dimorphic fig wasp species. Here I test the quantitative prediction in the fig wasp Pseudidarnes minerva. In addition, some fig wasp species that lack winged males, but have two wingless morphs, show a conditional strategy with morph determination influenced by the number of wasps developing in a patch. I also test for this alternative pattern in the wing-dimorphic P. minerva.

Results

I sampled 114 figs that contained a mean of 2.1 P. minerva wasps from 44 trees across four sites in Sydney, Australia. At the whole population level, the proportion of winged males (0.84 or 0.79 corrected for sampling bias) did not differ significantly from the proportion of unmated females (0.84), providing strong quantitative support for the prediction of Hamilton’s model. In addition, there was no evidence for other factors, such as local mate competition or fighting between wingless males, that could violate simplifying assumptions of the model. Meanwhile, the proportion of winged males was not correlated with the number of wasps per fig, providing no evidence for a conditional strategy.

Conclusion

The morph ratio in P. minerva is consistent with Hamilton’s simple Mendelian strategy model, where morph ratios are set by average mating opportunities at the population level. This contrasts with some fig wasps from another subfamily that show conditional morph determination, allowing finer scale adaptation to fig-level mating opportunities. However, these conditional cases do not involve wing polymorphism. Male polymorphism is common and variable in fig wasps and has evolved independently in multiple lineages with apparently different underlying mechanisms.
The impact of childhood RSV infection on children's and parents' quality of life: a prospective multicenter study in Spain
Authors: Díez-Gandía Eva , Gómez-Álvarez Carla , López-Lacort Mónica , Muñoz-Quiles Cintia , Úbeda-Sansano Isabel , Díez-Domingo Javier , Orrico-Sánchez Alejandro ,   Study collaborators, Rigual Fernando Calvo , Vicent Eva Suarez , Mañes Carmen , Martí Elena , Cerdán Teresa , Arandes Antonio Soriano , Pavón Lucia Losada , Sánchez Airam Álvarez , Furió Gemma Ricós , Porcuna Tomás Pérez , Benito Noemí Magro , Díaz Javier Martínez , Ortiz Jessica , Mangas Ana , García Mónica , Rovira Patricia , Urgellés Marta , Pozuelo Marta
Published: September 2021

Background

 Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefits of a potential vaccination programme, both economic and health benefits will be needed. Health benefits are usually measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no RSV-specific questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire administered online.

Methods

 An observational prospective multicentre surveillance study was conducted in children aged younger than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Catalonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints (day 0, 7, 14 and 30) after diagnosis.

Results

 117 children were enrolled in the study and 86 (73.5%) were RSV + . Median (interquartile range; IQR) scores were 0.52 (0.42–0.68), 0.65 (0.49–0.79), 0.82 (0.68–0.97) and 0.94 (0.81–1), for days 0, 7, 14 and 30, respectively. Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the disease. The total median cost per patient (including treatments) was €598.8 (IQR: 359.63–2425.85).

Conclusions

 RSV had almost 40% impact on HRQoL during the first week since onset of symptoms and the median cost per episode and patient was about €600. These results represent a substantial input for health-economic evaluations of future RSV-related interventions such as vaccination.
Gestational age as a predictor for subsequent preterm birth in New South Wales, Australia
Authors: Pereira Gavin , Regan Annette K. , Wong Kingsley , Tessema Gizachew A.
Published: September 2021

Background

There is no validated evidence base on predictive ability and absolute risk of preterm birth by gestational age of the previous pregnancy.

Methods

We conducted a retrospective cohort study of mothers who gave birth to their first two children in New South Wales, 1994–2016 (N = 517,558 mothers). For each week of final gestational age of the first birth, we calculated relative and absolute risks of subsequent preterm birth.

Results

For mothers whose first birth had a gestational age of 22 to 30 weeks the absolute risks of clinically significant preterm second birth (before 28, 32, and 34 weeks) were all less than 14%. For all gestational ages of the first child the median gestational ages of the second child were all at least 38 weeks. Sensitivity and positive predictive values were all below 30%.

Conclusion

Previous gestational age alone is a poor predictor of subsequent risk of preterm birth.
Metabolic engineering for high yield synthesis of astaxanthin in Xanthophyllomyces dendrorhous
Authors: Torres-Haro Alejandro , Verdín Jorge , Kirchmayr Manuel R. , Arellano-Plaza Melchor
Published: September 2021

Astaxanthin is a carotenoid with a number of assets useful for the food, cosmetic and pharmaceutical industries. Nowadays, it is mainly produced by chemical synthesis. However, the process leads to an enantiomeric mixture where the biologically assimilable forms (3R, 3′R or 3S, 3′S) are a minority. Microbial production of (3R, 3′R) astaxanthin by Xanthophyllomyces dendrorhous is an appealing alternative due to its fast growth rate and easy large-scale production. In order to increase X. dendrorhous astaxanthin yields, random mutant strains able to produce from 6 to 10 mg/g dry mass have been generated; nevertheless, they often are unstable. On the other hand, site-directed mutant strains have also been obtained, but they increase only the yield of non-astaxanthin carotenoids. In this review, we insightfully analyze the metabolic carbon flow converging in astaxanthin biosynthesis and, by integrating the biological features of X. dendrorhous with available metabolic, genomic, transcriptomic, and proteomic data, as well as the knowledge gained with random and site-directed mutants that lead to increased carotenoids yield, we propose new metabolic engineering targets to increase astaxanthin biosynthesis.