bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning from public health and hospital resilience to the SARS-CoV-2 pandemic: protocol for a multiple case study (Brazil, Canada, China, France, Japan, and Mali)
Authors: Ridde Valéry , Gautier Lara , Dagenais Christian , Chabrol Fanny , Hou Renyou , Bonnet Emmanuel , David Pierre-Marie , Cloos Patrick , Duhoux Arnaud , Lucet Jean-Christophe , Traverson Lola , de Araujo Oliveira Sydia Rosana , Cazarin Gisele , Peiffer-Smadja Nathan , Touré Laurence , Coulibaly Abdourahmane , Honda Ayako , Noda Shinichiro , Tamura Toyomitsu , Baba Hiroko , Kodoi Haruka , Zinszer Kate 
Published: May 2021

AbstractBackgroundAll prevention efforts currently being implemented for COVID-19 are aimed at reducing the burden on strained health systems and human resources. There has been little research conducted to understand how SARS-CoV-2 has affected health care systems and professionals in terms of their work. Finding effective ways to share the knowledge and insight between countries, including lessons learned, is paramount to the international containment and management of the COVID-19 pandemic. The aim of this project is to compare the pandemic response to COVID-19 in Brazil, Canada, China, France, Japan, and Mali. This comparison will be used to identify strengths and weaknesses in the response, including challenges for health professionals and health systems.MethodsWe will use a multiple case study approach with multiple levels of nested analysis. We have chosen these countries as they represent different continents and different stages of the pandemic. We will focus on several major hospitals and two public health interventions (contact tracing and testing). It will employ a multidisciplinary research approach that will use qualitative data through observations, document analysis, and interviews, as well as quantitative data based on disease surveillance data and other publicly available data. Given that the methodological approaches of the project will be largely qualitative, the ethical risks are minimal. For the quantitative component, the data being used will be made publicly available.DiscussionWe will deliver lessons learned based on a rigorous process and on strong evidence to enable operational-level insight for national and international stakeholders.
How to disseminate national recommendations for physical activity: a qualitative analysis of critical change agents in Germany
Authors: Wolbring Laura , Reimers Anne Kerstin , Niessner Claudia , Demetriou Yolanda , Schmidt Steffen Christian Ekkehard , Woll Alexander , Wäsche Hagen 
Published: May 2021

Abstract
Background
Physical activity recommendations are reached by only a small part of the population. A common problem is that research findings on public health-related topics such as physical activity promotion are oftentimes not translated into practice. The involvement of relevant stakeholders, such as change agents (role models, decision-makers, and/or knowledge mediators), is a common strategy to implement physical activity recommendations in specific settings, as they have the necessary knowledge of contextual factors. However, dissemination and implementation of physical activity recommendations are often prevented by focusing exclusively on the health sector and by underestimating the individual perceptions and needs of change agents. Therefore, the purpose of this study was to address the problem of how physical activity recommendations can be translated into practice through comprehensive consideration of the situation and context of change agents from various sectors of society at different administrative levels. This allows for deriving recommendations for action on how a national dissemination strategy of physical activity recommendations should be designed.

Methods
Qualitative expert interviews were conducted with change agents from different sectors of society and administrative levels in Germany (N = 21). Case selection took place via a sampling plan. The interviews were recorded, transcribed verbatim, and analysed by two trained researchers using qualitative content analysis.

Results
The change agents’ perceived relevance of physical activity and physical activity promotion and their knowledge of physical activity recommendations varied across different sectors. Nine themes were identified covering the change agents’ needs for the implementation of physical activity recommendations: strengthening of political will and cooperation, availability of public space for physical activity, change in awareness and health education, professional qualification, financial incentives, development of physical activity-promoting programmes and structures, provision of resources, bridging the theory–practice gap, and knowledge of physical activity recommendations.

Conclusions
This exploratory study contributes to the development of an evidence-based dissemination strategy of physical activity recommendations involving change agents from various sectors. Cross-sectoral needs and obstacles were identified indicating gaps that have to be addressed. Future research should choose practice-oriented approaches to develop dissemination strategies that are adapted to the needs of local contexts.
Conditional knockout of Tsc1 in RORγt-expressing cells induces brain damage and early death in mice
Authors: Deng Yafei , Yang Qinglan , Yang Yao , Li Yana , Peng Hongyan , Wu Shuting , Zhang Shuju , Yao Baige , Li Shuhui , Gao Yuan , Li Xiaohui , Li Liping , Deng Youcai 
Published: May 2021

Abstract
Background
Tuberous sclerosis complex 1 (Tsc1) is known to regulate the development and function of various cell types, and RORγt is a critical transcription factor in the immune system. However, whether Tsc1 participates in regulating RORγt-expressing cells remains unknown.

Methods
We generated a mouse model in which Tsc1 was conditionally deleted from RORγt-expressing cells (Tsc1RORγt) to study the role of RORγt-expressing cells with Tsc1 deficiency in brain homeostasis.

Results
Type 3 innate lymphoid cells (ILC3s) in Tsc1RORγt mice displayed normal development and function, and the mice showed normal Th17 cell differentiation. However, Tsc1RORγt mice exhibited spontaneous tonic-clonic seizures and died between 4 and 6 weeks after birth. At the age of 4 weeks, mice in which Tsc1 was specifically knocked out in RORγt-expressing cells had cortical neuron defects and hippocampal structural abnormalities. Notably, over-activation of neurons and astrogliosis were observed in the cortex and hippocampus of Tsc1RORγt mice. Moreover, expression of the γ-amino butyric acid (GABA) receptor in the brains of Tsc1RORγt mice was decreased, and GABA supplementation prolonged the lifespan of the mice to some extent. Further experiments revealed the presence of a group of rare RORγt-expressing cells with high metabolic activity in the mouse brain.

Conclusions
Our study verifies the critical role of previously unnoticed RORγt-expressing cells in the brain and demonstrates that the Tsc1 signaling pathway in RORγt-expressing cells is important for maintaining brain homeostasis.
Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways
Authors: Grytting Vegard Sæter , Refsnes Magne , Øvrevik Johan , Halle Marit Sigrid , Schönenberger Jasmin , van der Lelij Roelant , Snilsberg Brynhild , Skuland Tonje , Blom Richard , Låg Marit 
Published: May 2021

Abstract
Background
Respirable stone- and mineral particles may be a major constituent in occupational and ambient air pollution and represent a possible health hazard. However, with exception of quartz and asbestos, little is known about the toxic properties of mineral particles. In the present study, the pro-inflammatory and cytotoxic responses to six stone particle samples of different composition and with diameter below 10 μm were assessed in human bronchial epithelial cells (HBEC3-KT), THP-1 macrophages and a HBEC3-KT/THP-1 co-culture. Moreover, particle-induced lysis of human erythrocytes was assessed to determine the ability of the particles to lyse biological membranes. Finally, the role of the NLRP3 inflammasome was assessed using a NLRP3-specific inhibitor and detection of ASC oligomers and cleaved caspase-1 and IL-1β. A reference sample of pure α-quartz was included for comparison.

Results
Several stone particle samples induced a concentration-dependent increase in cytotoxicity and secretion of the pro-inflammatory cytokines CXCL8, IL-1α, IL-1β and TNFα. In HBEC3-KT, quartzite and anorthosite were the most cytotoxic stone particle samples and induced the highest levels of cytokines. Quartzite and anorthosite were also the most cytotoxic samples in THP-1 macrophages, while anorthosite and hornfels induced the highest cytokine responses. In comparison, few significant differences between particle samples were detected in the co-culture. Adjusting responses for differences in surface area concentrations did not fully account for the differences between particle samples. Moreover, the stone particles had low hemolytic potential, indicating that the effects were not driven by membrane lysis. Pre-incubation with a NLRP3-specific inhibitor reduced stone particle-induced cytokine responses in THP-1 macrophages, but not in HBEC3-KT cells, suggesting that the effects are mediated through different mechanisms in epithelial cells and macrophages. Particle exposure also induced an increase in ASC oligomers and cleaved caspase-1 and IL-1β in THP-1 macrophages, confirming the involvement of the NLRP3 inflammasome.

Conclusions
The present study indicates that stone particles induce cytotoxicity and pro-inflammatory responses in human bronchial epithelial cells and macrophages, acting through NLRP3-independent and -dependent mechanisms, respectively. Moreover, some particle samples induced cytotoxicity and cytokine release to a similar or greater extent than α-quartz. Thus, these minerals warrant further attention in future research.
A qualitative investigation into the impact of hemophagocytic lymphohistiocytosis on children and their caregivers
Authors: Nixon Annabel , Roddick Elina , Moore Karen , Wild Diane 
Published: May 2021

Abstract
Background
Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare and life-threatening disorder, which usually occurs during infancy or early childhood and is characterized by abnormal activation of the immune system. However, the burden of pHLH on children and their families has not been previously evaluated. This qualitative study investigated the impact of pHLH and its treatment on the physical, emotional, and social well-being of patients and caregivers in the USA and UK using interviews to provide a comprehensive insight from the perspective of the caregivers and young survivors.

Results
Twenty-one caregivers were enrolled (median [range] age, 41.1 [26–58] years) and represented 20 patients, four from the UK and 16 from the USA. At enrollment, 17 of the 20 patients were alive with a median [range] age of 12.75 [5–31] years at a mean [range] of 7.8 [0.6–11.6] years after diagnosis. In addition, four adult survivors (median [range] age, 23.3 [21–30] years) were also enrolled (total participants n = 25). From noticing initial symptoms to receiving a diagnosis, caregivers reported a mean (range) of 25.9 (0–258) months. pHLH and its treatment had a substantial and long-lasting impact on patients and caregivers, affecting their physical, emotional and social well-being, family relationships, friendships, and ability to work and study. Many of the experiences reported were negative, even after curative treatment, and some participants experienced long-lasting physical and emotional issues. The most noticeable impact of pHLH for patients was on their physical well-being, whereas for caregivers it was emotional well-being. Across all participants there was a sense of isolation due to the illness and its treatment, particularly regarding the patient being immunocompromised and the fear of infection. Areas having a major impact and considered in need of improvement included: delays in diagnosis, lack of patient-specific information on pHLH and a lack of support and understanding about the condition.

Conclusions
pHLH placed a substantial burden on patients and caregivers, which for some were long-lasting. This was compounded by the lack of awareness and understanding of pHLH by healthcare professionals, and a lack of accessible information for those affected by pHLH.
Genetic and environmental modulation of transposition shapes the evolutionary potential of Arabidopsis thaliana
Authors: Baduel Pierre , Leduque Basile , Ignace Amandine , Gy Isabelle , Gil José , Loudet Olivier , Colot Vincent , Quadrana Leandro 
Published: May 2021

AbstractBackgroundHow species can adapt to abrupt environmental changes, particularly in the absence of standing genetic variation, is poorly understood and a pressing question in the face of ongoing climate change. Here we leverage publicly available multi-omic and bio-climatic data for more than 1000 wildArabidopsis thalianaaccessions to determine the rate of transposable element (TE) mobilization and its potential to create adaptive variation in natural settings.ResultsWe demonstrate that TE insertions arise at almost the same rate as base substitutions. Mobilization activity of individual TE families varies greatly between accessions, in association with genetic and environmental factors as well as through complex gene-environment interactions. Although the distribution of TE insertions across the genome is ultimately shaped by purifying selection, reflecting their typically strong deleterious effects when located near or within genes, numerous recent TE-containing alleles show signatures of positive selection. Moreover, high rates of transposition appear positively selected at the edge of the species’ ecological niche. Based on these findings, we predict through mathematical modeling higher transposition activity in Mediterranean regions within the next decades in response to global warming, which in turn should accelerate the creation of large-effect alleles.ConclusionsOur study reveals that TE mobilization is a major generator of genetic variation inA. thalianathat is finely modulated by genetic and environmental factors. These findings and modeling indicate that TEs may be essential genomic players in the demise or rescue of native populations in times of climate crises.
Transgenerational effect of mutants in the RNA-directed DNA methylation pathway on the triploid block in Arabidopsis
Authors: Wang Zhenxing , Butel Nicolas , Santos-González Juan , Simon Lauriane , Wärdig Cecilia , Köhler Claudia 
Published: May 2021

Abstract
Background
Hybridization of plants that differ in number of chromosome sets (ploidy) frequently causes endosperm failure and seed arrest, a phenomenon referred to as triploid block. In Arabidopsis, loss of function of NRPD1, encoding the largest subunit of the plant-specific RNA polymerase IV (Pol IV), can suppress the triploid block. Pol IV generates short RNAs required to guide de novo methylation in the RNA-directed DNA methylation (RdDM) pathway. Recent work suggests that suppression of the triploid block by mutants in RdDM components differs, depending on whether the diploid pollen is derived from tetraploid plants or from the omission in second division 1 (osd1) mutant. This study aims to understand this difference.

Results
In this study, we find that the ability of mutants in the RdDM pathway to suppress the triploid block depends on their degree of inbreeding. While first homozygous generation mutants in RdDM components NRPD1, RDR2, NRPE1, and DRM2 have weak or no ability to rescue the triploid block, they are able to suppress the triploid block with successive generations of inbreeding. Inbreeding of nrpd1 was connected with a transgenerational loss of non-CG DNA methylation on sites jointly regulated by CHROMOMETHYLASES 2 and 3.

Conclusions
Our data reveal that loss of RdDM function differs in its effect in early and late generations, which has important implications when interpreting the effect of RdDM mutants.
Antibacterial and antioxidant activities of extracts and isolated compounds from the roots extract of Cucumis prophetarum and in silico study on DNA gyrase and human peroxiredoxin 5
Authors: Galma Wario , Endale Milkyas , Getaneh Emebet , Eswaramoorthy Rajalakshmanan , Assefa Temesgen , Melaku Yadessa 
Published: May 2021

AbstractBackgroundCucumis prophetarumis traditionally used to treat liver and lung disorders, heart failure, diarrhea, gonorrhea, skin infections, intestinal problems and cancer. In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time.MethodsSilica gel column chromatography was applied to separate constituents of the roots ofC. prophetarum.The structures of isolated compounds were established using1H NMR,13C NMR, DEPT-135, COSY, HSQC and HMBC. Agar well diffusion, DPPH assay and ferric thiocyante methods were used for antibacterial, radical scavenging and anti-lipid peroxidation activities, respectively. AutoDock Vina open source program was used for molecular docking analysis.ResultsEvaluation of the in vitro antibacterial activity of the constituents againstS. aureus, B. subtilis, E. coliandS. thyphimuriumrevealed that the hexane extract were active againstE. coliwith IZ of 15.0 ± 1.41 mm, whereas an IZ of 14.6 ± 1.70 mm for MeOH extract was observed againstS. aureus. Compound1displayed IZ of 13.6 ± 0.94 mm againstE. coliand curcurbiatin2showed activity againstB. subtiliswith IZ of 13.3 ± 0.54 mm. The molecular docking analysis showed that cucurbitacins2and3have binding energy of -6.7 and -6.9 kcal/mol, respectively. The methanol and the hexane extracts of the roots ofC. prophetaruminhibited DPPH radical by 70.4 and 63.3% at 100 µg/mL, respectively. On the other hand, the methanol extract inhibited lipid peroxidation by 53.0%.ConclusionThe present study identified five compounds from the root extracts ofC. prophetarum, of which two are novel cucurbitacins (1,2). The in vitro antibacterial activity of the hexane and methanol extracts was better than the activity displayed by the isolated compounds. This is probably due to the synergistic effects of the constituents present in the root extract. The in silico molecular docking study results showed that, compounds2and3have minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of DNA gyrase B. Furthermore, the “drug-likeness” and ADMET prediction of compounds2–5nearly showed compliance with the Lipinski rule, with good absorption, distribution, metabolism, and excretion generally. The radical scavenging and anti-lipid peroxidation activities of the extracts were better than the isolated compounds. This is attributed to the presence of phenolics and flavonoids as minor constituents in the extracts of these species. Therefore, the in vitro antibacterial activity and molecular docking analysis suggest the potential use of the isolated compounds as medicine which corroborates the traditional use of the roots ofC. prophetarum.
Real-time PCR biochip for on-site detection of Coxiella burnetii in ticks
Authors: Truong A.-Tai , Yun Bo-Ram , Lim Jiyeon , Min Subin , Yoo Mi-Sun , Yoon Soon-Seek , Yun Young-Min , Kim Jong-Taek , Cho Yun Sang 
Published: May 2021

AbstractBackgroundQ fever, a zoonosis caused byCoxiella burnetii, has adverse effects on public health. Ticks are vectors ofC. burnetiiand they contribute to the transmission of the pathogen. A tool for rapid, sensitive, and accurate detection ofC. burnetiifrom ticks is important for the prevention of Q fever.MethodsUltra-rapid real-time PCR (UR-qPCR) as a chip-based real-time PCR system was developed for the detection ofC. burnetiifrom ticks. The UR-qPCR system was established and evaluated for the rapidity, sensitivity, and specificity ofC. burnetiidetection.ResultsC. burnetiiwas detected using UR-qPCR from 5644 larval, nymphal, and adult ticks from 408 pools collected from livestock and epidemiologically linked environments in two provinces, Gangwon and Jeju, in Korea. Ticks from three species were identified;Haemaphysalis longicornisaccounted for the highest number, present in 333 of 408 pools (81.62%),followed byHaemaphysalis flavain 62 pools (15.19%) andIxodes nipponensisin 13 pools (3.19%). The rapidity and sensitivity of PCR detection was demonstrated with the sufficient amplification and detection of approximately 56 copies ofC. burnetiiDNA with only 20 min of PCR amplification. The kappa value for the diagnostic agreement between UR-qPCR and stationary qPCR was in perfect agreement (κ = 1). PCR detection and sequencing indicated thatC. burnetiiwas present in 5 of the 408 pools (1.23%), in which four pools containedH. longicornisand one pool containedH. flava. The infection rates ofC. burnetiiin the tick pools collected from Gangwon and Jeju Provinces were 1.70% and 0.58%, respectively. Phylogenetic analysis indicated a close relationship between the detectedC. burnetiiand those originating from goats, humans, and ticks in different countries, such as the USA, France, Germany, and Serbia.ConclusionsThe methods described in this study could be important for the prevention and control of Q fever in the two provinces. The UR-qPCR, with its features of mobility, sensitivity, and rapidity, is helpful for constructing early alert systems in the field forC. burnetiiin ticks and could help alleviate the transmission of and economic damage due to Q fever.Graphical Abstract