bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

AbstractAcute 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.