bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk stratification of ST-segment elevation myocardial infarction (STEMI) patients using machine learning based on lipid profiles
Authors: Xue Yuzhou , Shen Jian , Hong Weifeng , Zhou Wei , Xiang Zhenxian , Zhu Yuansong , Huang Chuiguo , Luo Suxin
Published: May 2021

Background

Numerous studies have revealed the relationship between lipid expression and increased cardiovascular risk in ST-segment elevation myocardial infarction (STEMI) patients. Nevertheless, few investigations have focused on the risk stratification of STEMI patients using machine learning algorithms.

Methods

A total of 1355 STEMI patients who underwent percutaneous coronary intervention were enrolled in this study during 2015–2018. Unsupervised machine learning (consensus clustering) was applied to the present cohort to classify patients into different lipid expression phenogroups, without the guidance of clinical outcomes. Kaplan-Meier curves were implemented to show prognosis during a 904-day median follow-up (interquartile range: 587–1316). In the adjusted Cox model, the association of cluster membership with all adverse events including all-cause mortality, all-cause rehospitalization, and cardiac rehospitalization was evaluated.

Results

All patients were classified into three phenogroups, 1, 2, and 3. Patients in phenogroup 1 with the highest Lp(a) and the lowest HDL-C and apoA1 were recognized as the statin-modified cardiovascular risk group. Patients in phenogroup 2 had the highest HDL-C and apoA1 and the lowest TG, TC, LDL-C and apoB. Conversely, patients in phenogroup 3 had the highest TG, TC, LDL-C and apoB and the lowest Lp(a). Additionally, phenogroup 1 had the worst prognosis. Furthermore, a multivariate Cox analysis revealed that patients in phenogroup 1 were at significantly higher risk for all adverse outcomes.

Conclusion

Machine learning-based cluster analysis indicated that STEMI patients with increased concentrations of Lp(a) and decreased concentrations of HDL-C and apoA1 are likely to have adverse clinical outcomes due to statin-modified cardiovascular risks.

Trial registration

ChiCTR1900028516 (http://www.chictr.org.cn/index.aspx).
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

Background

All 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.

Methods

We 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.

Discussion

We 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

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

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

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.
Correction to: Immunomodulatory effects of a new whole ingredients extract from Astragalus: a combined evaluation on chemistry and pharmacology
Authors: Li Zhi Xin , Zhao Guan Ding , Xiong Wei , Linghu Ke Gang , Ma Qiu Shuo , Cheang Wai San , Yu Hua , Wang Yitao
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
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

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

Background

How 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.

Results

We 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.

Conclusions

Our 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

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

Background

Cucumis 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.

Methods

Silica 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.

Results

Evaluation 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%.

Conclusion

The 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

Background

Q 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.

Methods

Ultra-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.

Results

C. 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.

Conclusions

The 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
Identification of neutrophil β2-integrin LFA-1 as a potential mechanistic biomarker in ANCA-associated vasculitis via microarray and validation analyses
Authors: Matsumoto Kotaro , Kurasawa Takahiko , Yoshimoto Keiko , Suzuki Katsuya , Takeuchi Tsutomu
Published: May 2021

Background

Leukocyte activation by anti-neutrophil cytoplasmic antibody (ANCA) and the subsequent leukocyte–endothelium interaction play a key role in the development of endothelial damage in ANCA-associated vasculitis (AAV). In contrast to that of leukocyte activation, the exact role of the leukocyte–endothelium interaction via integrin remains unclear. Here, we performed microarray and validation analyses to explore association between the expression levels of lymphocyte function-associated antigen-1 (LFA-1) and the clinical characteristics of patients with AAV.

Methods

We performed gene set enrichment analysis (GSEA) to identify the functional gene sets differentially expressed between patients with AAV and other types of vasculitis and the healthy controls (HCs). Flow cytometry was performed to validate the GSEA results. Treatment-naïve patients were monitored until 24 weeks of treatment. To examine the role of LFA-1 in the neutrophil–endothelium interaction, we performed a leukocyte adhesion and transmigration assay using peripheral blood and human umbilical vein endothelial cells (HUVECs).

Results

GSEA revealed that the molecular pathways involving integrin-related genes were significantly upregulated in patients with AAV compared to that in patients with other types of vasculitis and the HCs. Flow cytometry revealed that the percentage of neutrophils expressing LFA-1 was significantly higher in patients with AAV than in those with large-vessel vasculitis or polyarteritis nodosa and the HCs. LFA-1 levels in the neutrophils were higher in patients with MPO-ANCA-positive expression than in those with a positive PR3-ANCA expression and correlated with the peripheral eosinophil count, serum rheumatoid factor titre, serum C-reactive protein levels, and the vasculitis activity score of systemic and chest components. After 24 weeks of treatment, including prednisolone, cyclophosphamide, rituximab, azathioprine, methotrexate, and/or tacrolimus, neutrophil LFA-1 expression remained high in the non-responder patients, but decreased in the responder patients. The in vitro assay showed that leukocyte migration toward HUVECs was dependent on the interaction between LFA-1 and intercellular adhesion molecule-1 (ICAM1); the migration of leukocytes was inhibited by blocking the adhesion of LFA-1 to ICAM1.

Conclusions

The expression of LFA-1 in neutrophils is increased in patients with AAV. Neutrophil LFA-1 levels correlate with the clinical features of AAV. Inhibiting the adhesion of LFA-1 and ICAM1 impedes the neutrophil–endothelium interaction and may have a therapeutic role in AAV.
Decreased microRNA-155 in Behcet’s disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production
Authors: Liang Liang , Zhou Qingyun , Feng Lujia
Published: May 2021

Background

Earlier, we reported that the microRNA (miR)-155 expression in dendritic cells (DCs) from Behcet’s disease (BD) patients was decreased and affected cytokine production of DCs. In this study, we investigated the mechanisms whereby miR-155 regulates cytokine production by DCs.

Methods

The formation of autophagosomes in DCs was detected by transmission electron microscopy. Western blotting was used to detect the protein levels of LC3, Beclin-1, P62, p-mTOR, and p-Akt in DCs. TNF-α, IL-6, and IL-1β expression were investigated by ELISA. MiR-155 mimics were transfected to DCs to evaluate its effects on autophagy and cytokine production. RNA interference was used to downregulate the expression of TAB2.

Results

The formation of autophagosomes was found in DCs of active BD patients. The expressions of LC3-II, Beclin-1, and P62 were significantly increased in DCs of active BD patients compared to that of inactive BD patients and healthy controls. The expressions of IL-6, IL-1β, and TNF-α were significantly increased in DCs of active BD patients compared to that of healthy controls. The autophagy promoter (3-MA) and inhibitor (rapamycin) significantly decreased or increased the expression of TNF-α, IL-6, and IL-1β by DCs. The expression of LC3-II and Beclin-1 was significantly increased, but the expression of P62 proteins was decreased in DCs transfected with miR-155 mimics or after TAB2 was downregulated. The expression of TNF-α, IL-6, and IL-1β was decreased in DCs after miR-155 was upregulated or TAB2 was downregulated. The ratios of p-Akt/Akt and p-mTOR/mTOR were decreased in DCs after miR-155 was upregulated.

Conclusions

These results suggest that miR-155 affects the production of TNF-α, IL-6, and IL-1β by DCs through activation of the Akt/mTOR signaling pathway and by affecting the process of autophagy.
Extremely preterm birth and autistic traits in young adulthood: the EPICure study
Authors: O’Reilly Helen , Ni Yanyan , Johnson Samantha , Wolke Dieter , Marlow Neil
Published: May 2021

Background

A high prevalence of autism spectrum disorder is reported in children born extremely preterm (EP), but an even larger proportion of survivors are affected by subclinical difficulties than meet diagnostic criteria. The aims of this study were to investigate autistic traits associated with the broader autism phenotype in a cohort of young adults born EP, and explore how these traits relate to emotion recognition, empathy and autism symptom presentation in childhood. The prevalence of autism diagnoses was also investigated.

Methods

One hundred and twenty-nine young adults born before 26 weeks of gestation and 65 term-born controls participated in the 19-year follow-up phase of the EPICure studies. In addition to a clinical interview, participants completed the Broader Autism Phenotype Questionnaire (BAPQ), the Empathy Quotient questionnaire, and the Frankfurt Test and Training of Facial Affect Recognition. The Social Communication Questionnaire (SCQ) was completed by the participants’ parents at age 11 years.

Results

EP born young adults scored significantly higher on the BAPQ in comparison with their term-born peers, indicating greater autistic traits. Among EP participants, BAPQ scores were correlated with SCQ scores in childhood (r = 0.484, p < 0.001). EP young adults had significantly lower scores in emotion recognition and empathy in comparison with controls; however, this effect was mediated by IQ. At 19 years, a diagnosis of autism was reported by 10% of EP participants versus 1.6% of controls, whereas 31% of EP participants scored above the cut-off for the broader autism phenotype in comparison with 8.5% of term-born controls.

Limitations

The high attrition of EP participants from lower socio-economic backgrounds and with lower cognitive functioning may have led to an underrepresentation of those presenting with difficulties associated with autism.

Conclusions

A larger proportion of EP survivors are affected by difficulties associated with autism than have confirmed diagnoses, with a moderate correlation between autism symptom scores in childhood and autistic traits in young adulthood. EP young adults had significantly higher autism symptom scores and a larger proportion had a diagnosis of autism than controls. Screening for autistic traits at set points throughout childhood will help identify those EP individuals at risk of social difficulties who may benefit from intervention.
Large-cell neuroendocrine tumor of the prostate: a case report and review of the literature
Authors: Sleiman Walid , Karray Omar , Abi Abdallah Mikael , Bleichner-Perez Sarah , Kourda Jihen , Cosma-Opris Mihaela , Assouad Sabine , Riffaud Jean-Charles , Bart Stéphane , Coloby Patrick
Published: May 2021

Background

Primitive neuroendocrine prostate neoplasms are rarely reported. This entity comprises carcinoïd tumors and poorly differentiated neuroendocrine tumors, mainly those of the small-cell type. Large-cell-type primitive tumors are exceptional, and only nine cases are reported in the literature. Similar to neuroendocrine tumors of the prostate, large-cell-type primitive tumors may be observed in the context of conventional adenocarcinoma during androgen deprivation therapy or as prostatic metastasis of a distant neuroendocrine tumor, mainly pulmonary neoplasms.

Case presentation

We report a Caucasian case of a mixed prostatic carcinoma, with the largest component being the large-cell neuroendocine carcinoma, in a patient who underwent a total prostatectomy for a localized cancer. Diagnostic, histological, therapeutic and evolutive aspects are reported and discussed.

Conclusions

Large-cell primitive prostate neuroendocrine carcinoma is a rare but aggressive histological entity, which can be associated or not with an adenocarcinomatous component. Mixed forms have a better outcome, mainly when diagnosed at an early stage.
PINK1 contained in huMSC-derived exosomes prevents cardiomyocyte mitochondrial calcium overload in sepsis via recovery of mitochondrial Ca2+ efflux
Authors: Zhou Qin , Xie Min , Zhu Jing , Yi Qin , Tan Bin , Li Yasha , Ye Liang , Zhang Xinyuan , Zhang Ying , Tian Jie , Xu Hao
Published: May 2021

Background

Sepsis is a systemic inflammatory response to a local severe infection that may lead to multiple organ failure and death. Previous studies have shown that 40–50% of patients with sepsis have diverse myocardial injuries and 70 to 90% mortality rates compared to 20% mortality in patients with sepsis without myocardial injury. Therefore, uncovering the mechanism of sepsis-induced myocardial injury and finding a target-based treatment are immensely important.

Objective

The present study elucidated the mechanism of sepsis-induced myocardial injury and examined the value of human umbilical cord mesenchymal stem cells (huMSCs) for protecting cardiac function in sepsis.

Methods

We used cecal ligation and puncture (CLP) to induce sepsis in mice and detect myocardial injury and cardiac function using serological markers and echocardiography. Cardiomyocyte apoptosis and heart tissue ultrastructure were detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) and transmission electron microscopy (TEM), respectively. Fura-2 AM was used to monitor Ca2+ uptake and efflux in mitochondria. FQ-PCR and Western blotting detected expression of mitochondrial Ca2+ distribution regulators and PTEN-induced putative kinase 1 (PINK1). JC-1 was used to detect the mitochondrial membrane potential (Δψm) of cardiomyocytes.

Results

We found that expression of PINK1 decreased in mouse hearts during sepsis, which caused cardiomyocyte mitochondrial Ca2+ efflux disorder, mitochondrial calcium overload, and cardiomyocyte injury. In contrast, we found that exosomes isolated from huMSCs (huMSC-exo) carried Pink1 mRNA, which could be transferred to recipient cardiomyocytes to increase PINK1 expression. The reduction in cardiomyocyte mitochondrial calcium efflux was reversed, and cardiomyocytes recovered from injury. We confirmed the effect of the PINK1-PKA-NCLX axis on mitochondrial calcium homeostasis in cardiomyocytes during sepsis.

Conclusion

The PINK1-PKA-NCLX axis plays an important role in mitochondrial calcium efflux in cardiomyocytes. Therefore, PINK1 may be a therapeutic target to protect cardiomyocyte mitochondria, and the application of huMSC-exo is a promising strategy against sepsis-induced heart dysfunction.
ASCs derived from burn patients are more prone to increased oxidative metabolism and reactive oxygen species upon passaging
Authors: Burmeister David M. , Chu Grace Chu-Yuan , Chao Tony , Heard Tiffany C. , Gómez Belinda I. , Sousse Linda E. , Natesan Shanmugasundaram , Christy Robert J.
Published: May 2021

Background

Patients with severe burn injury (over 20% of the total body surface area) experience profound hypermetabolism which significantly prolongs wound healing. Adipose-derived stem cells (ASCs) have been proposed as an attractive solution for treating burn wounds, including the potential for autologous ASC expansion. While subcutaneous adipocytes display an altered metabolic profile post-burn, it is not known if this is the case with the stem cells associated with the adipose tissue.

Methods

ASCs were isolated from discarded burn skin of severely injured human subjects (BH, n = 6) and unburned subcutaneous adipose tissue of patients undergoing elective abdominoplasty (UH, n = 6) and were analyzed at passages 2, 4, and 6. Flow cytometry was used to quantify ASC cell surface markers CD90, CD105, and CD73. Mitochondrial abundance and reactive oxygen species (ROS) production were determined with MitoTracker Green and MitoSOX Red, respectively, while JC-10 Mitochondrial Membrane Potential Assays were also performed. Mitochondrial respiration and glycolysis were analyzed with a high-resolution respirometer (Seahorse XFe24 Analyzer).

Results

There was no difference in age between BH and UH (34 ± 6 and 41 ± 4 years, respectively, P = 0.49). While passage 2 ASCs had lower ASC marker expression than subsequent passages, there were no significant differences in the expression between BH and UH ASCs. Similarly, no differences in mitochondrial abundance or membrane potential were found amongst passages or groups. Two-way ANOVA showed a significant effect (P < 0.01) of passaging on mitochondrial ROS production, with increased ROS in BH ASCs at later passages. Oxidative phosphorylation capacities (leak and maximal respiration) increased significantly in BH ASCs (P = 0.035) but not UH ASCs. On the contrary, basal glycolysis significantly decreased in BH ASCs (P = 0.011) with subsequent passaging, but not UH ASCs.

Conclusions

In conclusion, ASCs from burned individuals become increasingly oxidative and less glycolytic upon passaging when compared to ASCs from unburned patients. This increase in oxidative capacities was associated with ROS production in later passages. While the autologous expansion of ASCs holds great promise for treating burned patients with limited donor sites, the potential negative consequences of using them require further investigation.
Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis
Authors: Li Yanju , Wang Feiqing , Liang Huiling , Tang Dongxin , Huang Mei , Zhao Jianing , Yang Xu , Liu Yanqing , Shu Liping , Wang Jishi , He Zhixu , Liu Yang
Published: May 2021

Background

This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM).

Methods

We systematically searched PubMed, ScienceDirect, Google Scholar, CNKI, EMBASE, Web of Science, MEDLINE, and the Cochrane Library for studies published from the establishment of the databases to November 2020. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed- or random-effects models.

Results

We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239 participants) to examine the efficacy of mesenchymal stem cells (MSCs) therapy in the treatment of diabetes mellitus. According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated group was significantly lower than it was at baseline (mean difference (MD) = −1.51, 95% CI −2.42 to −0.60, P = 0.001). The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the control group (SMD = 0.89, 95% CI 0.36 to 1.42, P = 0.001), and their insulin requirement was significantly lower than it was at baseline (SMD = −1.14, 95% CI −1.52 to −0.77, P < 0.00001).

Conclusion

Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially T1DM, and no obvious adverse reactions.
Predictors of the prolonged recovery period in COVID-19 patients: a cross-sectional study
Authors: SeyedAlinaghi SeyedAhmad , Abbasian Ladan , Solduzian Mohammad , Ayoobi Yazdi Niloofar , Jafari Fatemeh , Adibimehr Alireza , Farahani Aazam , Salami Khaneshan Arezoo , Ebrahimi Alavijeh Parvaneh , Jahani Zahra , Karimian Elnaz , Ahmadinejad Zahra , Khalili Hossein , Seifi Arash , Ghiasvand Fereshteh , Ghaderkhani Sara , Rasoolinejad Mehrnaz
Published: May 2021

Background

The clinical course of COVID-19 may vary significantly. The presence of comorbidities prolongs the recovery time. The recovery in patients with mild-to-moderate symptoms might take 10 days, while in those with a critical illness or immunocompromised status could take 15 days. Considering the lack of data about predictors that could affect the recovery time, we conducted this study to identify them.

Methods

This cross-sectional study was implemented in the COVID-19 clinic of a teaching and referral university hospital in Tehran. Patients with the highly suggestive symptoms who had computed tomography (CT) imaging results with typical findings of COVID-19 or positive results of reverse transcriptase-polymerase chain reaction (RT-PCR) were enrolled in the study. Inpatient and outpatient COVID-19 participants were followed up by regular visits or phone calls, and the recovery period was recorded.

Results

A total of 478 patients were enrolled. The mean age of patients was 54.11 ± 5.65 years, and 44.2% were female. The median time to recovery was 13.5 days (IQR: 9). Although in the bivariate analysis, multiple factors, including hypertension, fever, diabetes mellitus, gender, and admission location, significantly contributed to prolonging the recovery period, in multivariate analysis, only dyspnea had a significant association with this variable (p = 0.02, the adjusted OR of 2.05; 95% CI 1.12–3.75).

Conclusion

This study supports that dyspnea is a predictor of recovery time. It seems like optimal management of the comorbidities plays the most crucial role in recovery from COVID-19.
The social issues of smart home: a review of four European cities’ experiences
Authors: Pira Saeid
Published: May 2021

The urban industrialization trend and the increasing urban population have posed global and local concerns related to urban management. Today, scientists introduce the “smart city” concept, among many others. The primary concept purpose is to empower cities to enhance the quality of life of their residents. To achieve this, one of the smart city components named “smart living” has a direct connection to citizens’ quality of life. This research aims to analyze the smart home as one of the sub-components of smart living. Consequently, based on the “smart home” residents’ viewpoint, the main question is which social barriers are more critical?

To achieve this essay’s objectives, the researcher conducts three phases: data collection, analysis based on the constructed conceptual model, and results. The researcher selected four leading smart cities in Europe, including Copenhagen, Berlin, London, and Barcelona, as case studies. The study collected primary data by cluster-random sampling by utilizing a questionnaire survey with 320 participants. In conclusion, according to the inhabitants, the research results list the most significant social challenges in smart homes. Eventually, suggestions offer for reducing the side effect of living in a smart home.
Current views on the genetic landscape and management of variant acute promyelocytic leukemia
Authors: Zhang Xiang , Sun Jiewen , Yu Wenjuan , Jin Jie
Published: May 2021

Acute promyelocytic leukemia (APL) is characterized by the accumulation of promyelocytes in bone marrow. More than 95% of patients with this disease belong to typical APL, which express PML-RARA and are sensitive to differentiation induction therapy containing all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and they exhibit an excellent clinical outcome. Compared to typical APL, variant APL showed quite different aspects, and how to recognize, diagnose, and treat variant APL remained still challenged at present. Herein, we drew the genetic landscape of variant APL according to recent progresses, then discussed how they contributed to generate APL, and further shared our clinical experiences about variant APL treatment. In practice, when APL phenotype was exhibited but PML-RARA and t(15;17) were negative, variant APL needed to be considered, and fusion gene screen as well as RNA-sequencing should be displayed for making the diagnosis as soon as possible. Strikingly, we found that besides of RARA rearrangements, RARB or RARG rearrangements also generated the phenotype of APL. In addition, some MLL rearrangements, NPM1 rearrangements or others could also drove variant APL in absence of RARA/RARB/RARG rearrangements. These results indicated that one great heterogeneity existed in the genetics of variant APL. Among them, only NPM1-RARA, NUMA-RARA, FIP1L1-RARA, IRF2BP2-RARA, and TFG-RARA have been demonstrated to be sensitive to ATRA, so combined chemotherapy rather than differentiation induction therapy was the standard care for variant APL and these patients would benefit from the quick switch between them. If ATRA-sensitive RARA rearrangement was identified, ATRA could be added back for re-induction of differentiation. Through this review, we hoped to provide one integrated view on the genetic landscape of variant APL and helped to remove the barriers for managing this type of disease.