bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 addressedIn 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.MethodsGeneral 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.ResultsCompliance 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 questionWearing 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

BackgroundPatients 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.MethodsA 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.Results14 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.ConclusionFan 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

Abstract
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

Abstract
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

Abstract
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

AbstractAstaxanthin 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.
TAZ maintains telomere length in TNBC cells by mediating Rad51C expression
Authors: Yang Lu , Wang Bo , Jiao Xinyan , Zhou Can , Chen Su , Gao Xiaoqian , Sun Wei , Song Shaoran , Li Juan , Liu Jie , Wang Yaochun , Liu Peijun 
Published: September 2021

Abstract
Background
Telomere maintenance is crucial for the unlimited proliferation of cancer cells and essential for the “stemness” of multiple cancer cells. TAZ is more extensively expressed in triple negative breast cancers (TNBC) than in other types of breast cancers, and promotes proliferation, transformation and EMT of cancer cells. It was reported that TAZ renders breast cancer cells with cancer stem cell features. However, whether TAZ regulates telomeres is still unclear. In this study, we explored the roles of TAZ in the regulation of telomere maintenance in TNBC cells.

Methods
siRNA and shRNA was used to generate TAZ-depleted TNBC cell lines. qPCR and Southern analysis of terminal restriction fragments techniques were used to test telomere length. Co-immunoprecipitation, Western blotting, immunofluorescence, Luciferase reporter assay and Chromatin-IP were conducted to investigate the underlying mechanism.

Results
By knocking down the expression of TAZ in TNBC cells, we found, for the first time, that TAZ is essential for the maintenance of telomeres in TNBC cells. Moreover, loss of TAZ causes senescence phenotype of TNBC cells. The observed extremely shortened telomeres in late passages of TAZ knocked down cells correlate with an elevated hTERT expression, reductions of shelterin proteins, and an activated DNA damage response pathway. Our data also showed that depletion of TAZ results in overexpression of TERRAs, which are a group of telomeric repeat‐containing RNAs and regulate telomere length and integrity. Furthermore, we discovered that TAZ maintains telomere length of TNBC cells likely by facilitating the expression of Rad51C, a crucial element of homologous recombination pathway that promotes telomere replication.

Conclusions
This study supports the notion that TAZ is an oncogenic factor in TNBC, and further reveals a novel telomere-related pathway that is employed by TAZ to regulate TNBC.
Comparing accuracy of bedside ultrasound examination with physical examination for detection of pleural effusion
Authors: Walsh Michael H. , Zhang Kang X. , Cox Emily J. , Chen Justin M. , Cowley Nicholas G. , Oleynick Christopher J. , Smyth Leo M. , Ma Irene W. Y. 
Published: September 2021

Abstract
Background
In detecting pleural effusion, bedside ultrasound (US) has been shown to be more accurate than auscultation. However, US has not been previously compared to the comprehensive physical examination. This study seeks to compare the accuracy of physical examination with bedside US in detecting pleural effusion.

Methods
This study included a convenience sample of 34 medical inpatients from Calgary, Canada and Spokane, USA, with chest imaging performed within 24 h of recruitment. Imaging results served as the reference standard for pleural effusion. All patients underwent a comprehensive lung physical examination and a bedside US examination by two researchers blinded to the imaging results.

Results
Physical examination was less accurate than US (sensitivity of 44.0% [95% confidence interval (CI) 30.0–58.8%], specificity 88.9% (95% CI 65.3–98.6%), positive likelihood (LR) 3.96 (95% CI 1.03–15.18), negative LR 0.63 (95% CI 0.47–0.85) for physical examination; sensitivity 98% (95% CI 89.4–100%), specificity 94.4% (95% CI 72.7–99.9%), positive LR 17.6 (95% CI 2.6–118.6), negative LR 0.02 (95% CI 0.00–0.15) for US). The percentage of examinations rated with a confidence level of 4 or higher (out of 5) was higher for US (85% of the seated US examination and 94% of the supine US examination, compared to 35% of the PE, P < 0.001), and took less time to perform (P < 0.0001).

Conclusions
US examination for pleural effusion was more accurate than the physical examination, conferred higher confidence, and required less time to complete.
Cross-education and detraining effects of eccentric vs. concentric resistance training of the elbow flexors
Authors: Sato Shigeru , Yoshida Riku , Kiyono Ryosuke , Yahata Kaoru , Yasaka Koki , Nosaka Kazunori , Nakamura Masatoshi 
Published: September 2021

Abstract
Background
Unilateral resistance training increases the strength of the contralateral non-trained homologous muscles known as the cross-education effect. We tested the hypothesis that unilateral eccentric resistance training (ET) would induce greater and longer-lasting cross-education effect when compared with concentric resistance training (CT).

Methods
Young (20–23 y) participants were allocated to ET (5 males, 4 females) or CT (5 males, 4 females) group that performed unilateral progressive ET or CT of the elbow flexors, twice a week for 5 weeks (10 sessions) followed by a 5-week detraining, and control group (7 males, 6 females) that did not perform any training. Maximum voluntary isometric contraction torque of the elbow flexors (MVIC), one-repetition maximum of concentric dumbbell curl (1-RM), and biceps brachii and brachialis muscle thickness (MT) were measured from the trained and non-trained arms before, several days after the last training session, and 5 weeks later. A ratio between the trained and non-trained arms for the change in MVIC or 1-RM from pre- to post-training (cross-body transfer ratio) was compared between ET and CT groups.

Results
The control group did not show significant changes in any variables. Both ET and CT increased (P < 0.05) MVIC (22.5 ± 12.3 % vs. 26.0 ± 11.9 %) and 1-RM (28.8 ± 6.6 % vs. 35.4 ± 12.9 %) of the trained arm without a significant difference between groups. MVIC was maintained after detraining for ET but returned to the baseline for CT, and 1-RM was maintained after detraining for both ET and CT. For the non-trained arm, MVIC (22.7 ± 17.9 % vs. 12.2 ± 10.2 %) and 1-RM (19.9 ± 14.6 % vs. 24.0 ± 10.6 %) increased similarly (P > 0.05) after ET and CT, and MVIC returned to the baseline after detraining, but 1-RM was maintained for both groups. An increase (P < 0.05) in MT was found only after ET for the trained arm (7.1 ± 6.1 %). The cross-body transfer ratio for MVIC was greater (P < 0.05) for ET (90.9 ± 46.7 %) than CT (49.0 ± 30.0 %).

Conclusions
These results did not support the hypothesis and showed similar changes in the most of the variables between ET and CT for the trained and non-trained arms, and strong cross-education effects on MVIC and 1-RM, but less detraining effect after ET than CT on MVIC of the trained arm.

Trial registration
University Hospital Medical Information Network Clinical Trials Registry (UMIN000044477; Jun 09, 2021).
Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging
Authors: Reseco Lucia , Atienza Mercedes , Fernandez-Alvarez Marina , Carro Eva , Cantero Jose L. 
Published: September 2021

AbstractBackgroundAging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer’s disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with deterioration of the immune system requires from non-invasive biomarkers able to detect failures in the brain-immunity connection. Reduced levels of salivary lactoferrin (sLF), an iron-binding protein with immunomodulatory activity, have been related to AD diagnosis. However, it remains unknown whether decreased sLF is associated with increased cortical amyloid-beta (Aβ) load and/or with loss of cortical integrity in normal aging.MethodsSeventy-four cognitively normal older adults (51 females) participated in the study. We applied multiple linear regression analyses to assess (i) whether sLF is associated with cortical Aβ load measured by 18F-Florbetaben (FBB)-positron emission tomography (PET), (ii) whether sLF-related variations in cortical thickness and cortical glucose metabolism depend on global Aβ burden, and (iii) whether such sLF-related cortical abnormalities moderate the relationship between sLF and cognition.ResultssLF was negatively associated with Aβ load in parieto-temporal regions. Moreover, sLF was related to thickening of the middle temporal cortex, increased FDG uptake in the posterior cingulate cortex, and poorer memory. These associations were stronger in individuals showing the highest Aβ burden.ConclusionssLF levels are sensitive to variations in cortical Aβ load, structural and metabolic cortical abnormalities, and subclinical memory impairment in asymptomatic older adults. These findings provide support for the use of sLF as a non-invasive biomarker of cerebral vulnerability in the general aging population.