bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary spastic angina after the administration of intravenous immunoglobulin in myasthenia gravis: a case report
Authors: Yanagihashi Masaru , Okamoto Ryuichi , Morioka Harumi , Sawada Masahiro , Matsumoto Shingo , Ikeda Takanori , Kano Osamu 
Published: August 2020

Abstract
Background
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies that block or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Most of MG patients need immunosuppression agents in addition to treatments that alleviate the symptoms. Intravenous immunoglobulin (IVIg) and plasma exchange are specific treatments given to patients with severe MG and myasthenia gravis crisis. IVIg therapy can cause an increase in serum viscosity; therefore, the risk for thromboembolic events, such as stroke, myocardial infarction, and pulmonary embolism, are reported after IVIg therapy.

Case presentation
An MG patient was treated with pyridostigmine bromide and prednisolone. The patient’s symptoms worsened 26 days after the commencement of treatment and was presented with head drop and dyspnea. The patient was diagnosed with MG crisis and IVIg was initiated. However, the patient reported chest pain and dyspnea 3 days after IVIg had started. An electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A cardiac catheterization was performed and stenosis, obstruction, and sclerosis were ruled out. Glyceryl trinitrate relieved the patient’s symptoms, suggesting coronary spastic angina (CSA).

Conclusions
We report the first case of CSA after IVIg. Practitioners should be aware of the potential risks of CSA when administering IVIg for MG patients, in particular in old patients with vascular risk factors.
Genetic profile of African swine fever virus responsible for the 2019 outbreak in northern Malawi
Authors: Hakizimana J. N. , Kamwendo G. , Chulu J. L. C. , Kamana O. , Nauwynck H. J. , Misinzo G. 
Published: August 2020

Abstract
Background
African swine fever (ASF) is an infectious transboundary animal disease which causes high mortality, approaching 100% in domestic pigs and it is currently considered as the most serious constraint to domestic pig industry and food security globally. Despite regular ASF outbreaks within Malawi, few studies have genetically characterized the causative ASF virus (ASFV). This study aimed at genetic characterization of ASFV responsible for the 2019 outbreak in northern Malawi. The disease confirmation was done by polymerase chain reaction (PCR) followed by molecular characterization of the causative ASFV by partial genome sequencing and phylogenetic reconstruction of the B646L (p72) gene, nucleotide alignment of the intergenic region (IGR) between I73R and I329L genes and translation of the central variable region (CVR) coded by B602L gene.

Results
All thirteen samples collected during this study in Karonga district in September 2019 were ASFV-positive and after partial genome sequencing and phylogenetic reconstruction of the B646L (p72) gene, the viruses clustered into ASFV p72 genotype II. The viruses characterized in this study lacked a GAATATATAG fragment between the I173R and the I329L genes and were classified as IGR I variants. Furthermore, the tetrameric amino acid repeats within the CVR of the B602L gene of the 2019 Malawian ASFV reported in this study had the signature BNDBNDBNAA, 100% similar to ASFV responsible for the 2013 and 2017 ASF outbreaks in Zambia and Tanzania, respectively.

Conclusions
The results of this study confirm an ASF outbreak in Karonga district in northern Malawi in September 2019. The virus was closely related to other p72 genotype II ASFV that caused outbreaks in neighboring eastern and southern African countries, emphasizing the possible regional transboundary transmission of this ASFV genotype. These findings call for a concerted regional and international effort to control the spread of ASF in order to improve nutritional and food security.
Coxiella burnetii is widespread in ticks (Ixodidae) in the Xinjiang areas of China
Authors: Ni Jun , Lin Hanliang , Xu Xiaofeng , Ren Qiaoyun , Aizezi Malike , Luo Jin , Luo Yi , Ma Zhan , Chen Ze , Tan Yangchun , Guo Junhui , Liu Wenge , Qu Zhiqiang , Wu Zegong , Wang Jinming , Li Youquan , Guan Guiquan , Luo Jianxun , Yin Hong , Liu Guangyuan 
Published: August 2020

Abstract
Background
The gram-negative Coxiella burnetii bacterium is the pathogen that causes Q fever. The bacterium is transmitted to animals via ticks, and manure, air, dead infected animals, etc. and can cause infection in domestic animals, wild animals, and humans. Xinjiang, the provincial-level administrative region with the largest land area in China, has many endemic tick species. The infection rate of C. burnetii in ticks in Xinjiang border areas has not been studied in detail.

Results
For the current study, 1507 ticks were collected from livestock at 22 sampling sites in ten border regions of the Xinjiang Uygur Autonomous region from 2018 to 2019. C. burnetii was detected in 205/348 (58.91%) Dermacentor nuttalli; in 110/146 (75.34%) D. pavlovskyi; in 66/80 (82.50%) D. silvarum; in 15/32 (46.90%) D. niveus; in 28/132 (21.21%) Hyalomma rufipes; in 24/25 (96.00%) H. anatolicum; in 219/312 (70.19%) H. asiaticum; in 252/338 (74.56%) Rhipicephalus sanguineus; and in 54/92 (58.70%) Haemaphysalis punctata. Among these samples, C. burnetii was detected in D. pavlovskyi for the first time. The infection rate of Rhipicephalus was 74.56% (252/338), which was the highest among the four tick genera sampled, whereas the infection rate of H. anatolicum was 96% (24/25), which was the highest among the nine tick species sampled. A sequence analysis indicated that 63 16S rRNA sequences could be found in four newly established genotypes: MT498683.1 (n = 18), MT498684.1 (n = 33), MT498685.1 (n = 6), and MT498686.1 (n = 6).

Conclusions
This study indicates that MT498684.1 might represent the main C. burnetii genotype in the ticks in Xinjiang because it was detected in eight of the tick species studied. The high infection rate of C. burnetii detected in the ticks found in domestic animals may indicate a high likelihood of Q fever infection in both domestic animals and humans.
Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models
Authors: Nolan Kyle , Verzosa Gregory , Cleaver Tim , Tippimanchai Darinee , DePledge Lisa N. , Wang Xiao-Jing , Young Christian , Le Anh , Doebele Robert , Li Howard , Malkoski Stephen P. 
Published: August 2020

AbstractBackgroundImmunocompetent animal models are required to study tumor-host interactions, immunotherapy, and immunotherapeutic combinations, however the currently available immunocompetent lung cancer models have substantial limitations. While orthotopic models potentially help fill this gap, the utility of these models has been limited by the very small number of murine lung cancer cell lines capable of forming orthotopic tumors in immunocompetent C57BL/6 hosts.MethodsPrimary lung tumors with specific genetic alterations were created in C57BL/6 background mice. These tumors were then passaged through other animals to increase tumorigenicity and select for the ability to grow in a non-self animal. Once tumors demonstrated growth in a non-self host, cell lines were established. Successful cell lines were evaluated for the ability to produce orthotopic lung tumors in immunocompetent hosts.ResultsWe produced six murine lung cancer lines capable of orthotopic lung tumor formation in immunocompetent C57BL/6 animals. These lines demonstrate the expected genetic alterations based on their primary tumor genetics.ConclusionsThese novel cell lines will be useful for evaluating tumor-host interactions, the impact of specific oncogenic alterations on the tumor microenvironment, and immunotherapeutic approaches. This method of generating murine lines capable of orthotopic growth can likely be applied to other tumors and will broaden the applicability of pre-clinical testing of immunotherapeutic treatment regimens.
Calcineurin
Authors: Creamer Trevor P. 
Published: August 2020

AbstractThe serine/threonine phosphatase calcineurin acts as a crucial connection between calcium signaling the phosphorylation states of numerous important substrates. These substrates include, but are not limited to, transcription factors, receptors and channels, proteins associated with mitochondria, and proteins associated with microtubules. Calcineurin is activated by increases in intracellular calcium concentrations, a process that requires the calcium sensing protein calmodulin binding to an intrinsically disordered regulatory domain in the phosphatase. Despite having been studied for around four decades, the activation of calcineurin is not fully understood. This review largely focuses on what is known about the activation process and highlights aspects that are currently not understood.
Social ecological factors associated with physical activity and screen time amongst mothers from disadvantaged neighbourhoods over three years
Authors: Morris Kylie A. , Arundell Lauren , Cleland Verity , Teychenne Megan 
Published: August 2020

Abstract
Background
Mothers from socioeconomically disadvantaged neighbourhoods are at elevated risk of physical inactivity and high levels of screen time. Yet, little is known regarding the social ecological factors that are longitudinally associated with physical activity and screen time in this target group, and whether the age of their children impacts these relationships. This study aimed to longitudinally examine the social ecological factors associated with physical activity and screen time amongst mothers living in socioeconomically disadvantaged neighbourhoods, and whether these differed according to their child’s age.

Methods
Data were from 895 mothers living in socioeconomically disadvantaged neighbourhoods (mean age 36.7 years) at baseline and three-year follow-up. Mothers self-reported weekly discretionary physical activity (leisure-time, LTPA; transport-related, TRPA) and screen time durations. Linear regression models assessed associations between five intrapersonal, three social and five physical environmental factors and LTPA, TRPA and screen time, adjusting for confounding factors, clustering by neighbourhood and baseline variables. Interaction analysis was conducted for age of children (younger and older children (n = 442) and mothers with older children (aged 5–12 years) only (n = 453).

Results
In adjusted models, all intrapersonal factors (self-efficacy, enjoyment, outcome expectations, behavioural intentions and behavioural skill), social support from friends, neighbourhood cohesion and number of televisions were longitudinally associated with LTPA amongst all mothers. Interaction models showed that findings were generally consistent across groups (i.e., those with both younger and older children compared to those with older children only), with three exceptions. Physical activity enjoyment and social support from family were associated with LTPA only among mothers with older children. Neighbourhood cohesion was associated with screen time only amongst mothers with both younger and older children. No associations were detected for TRPA.

Conclusion
Intrapersonal, social and physical environmental factors were longitudinally associated with mother’s LTPA, whilst neighbourhood cohesion was longitudinally associated with screen time behaviours amongst mothers. Interventions aimed at increasing LTPA amongst mothers (particularly those from socioeconomically disadvantaged neighbourhoods) may need to target all domains of the social ecological model and may require some tailoring according to the age of children. Further work is needed to identify longitudinal associations with screen time and TRPA in this population group.
Analyzing and validating the prognostic value and mechanism of colon cancer immune microenvironment
Authors: Wang Xinyi , Duanmu Jinzhong , Fu Xiaorui , Li Taiyuan , Jiang Qunguang 
Published: August 2020

Abstract
Background
Colon cancer is a disease with high malignancy and incidence in the world. Tumor immune microenvironment (TIM) and tumor mutational burden (TMB) have been proved to play crucial roles in predicting clinical outcomes and therapeutic efficacy, but the correlation between them and the underlying mechanism were not completely understood in colon cancer.

Methods
In this study, we used Single-Sample Gene Set Enrichment Analysis (ssGSEA) and unsupervised consensus clustering analysis to divide patients from the TCGA cohort into three immune subgroups. Then we validated their differences in immune cell infiltration, overall survival outcomes, clinical phenotypes and expression levels of HLA and checkpoint genes by Mann–Whitney tests. We performed weighted correlation network analysis (WGCNA) to obtain immunity-related module and hub genes. Then we explored the underlying mechanism of hub genes by gene set enrichment analysis (GSEA) and gene set evaluation analysis (GSVA). Finally, we gave an overall view of gene variants and verified the correlation between TIM and TMB by comparing microsatellite instability (MSI) and gene mutations among three immune subgroups.

Results
The colon cancer patients were clustered into low immunity, median immunity and high immunity groups. The median immunity group had a favorable survival probability compared with that of the low and high immunity groups. Three groups had significant differences in immune cell infiltration, tumor stage, living state and T classification. We got 8 hub genes (CCDC69, CLMP, FAM110B, FAM129A, GUCY1B3, PALLD, PLEKHO1 and STY11) and predicted that immunity may correlated with inflammatory response, KRAS signaling pathway and T cell infiltration. With higher immunity, the TMB was higher. The most frequent mutations in low and median immunity groups were APC, TP53 and KRAS, while TTN and MUC16 showed higher mutational frequency in high immunity group.

Conclusions
We performed a comprehensive evaluation of the immune microenvironment landscape of colon cancer and demonstrated the positive correlation between immunity and TMB. The hub genes and frequently mutated genes were strongly related to immunity and may give suggestion for immunotherapy in the future.
Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma
Authors: Qin Xia , Zhang Jian , Lin Yu , Sun Xue-ming , Zhang Jia-ning , Cheng Zhi-qiang 
Published: August 2020

Abstract
Background
Liver cancer is among the most common malignancy worldwide. Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. The high rates of recurrence and metastasis contribute to the poor prognosis of HCC patients. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC.

Methods
To screen for key candidate miRNAs in HCC, three microarray datasets were downloaded from Gene Expression Omnibus (GEO). The sole common differentially expressed miRNA (DEmiR) observed in the above three datasets using a Venn diagram was microRNA-211-5p (miR-211-5p). The expression of miR-211-5p from HCC tissues was measured in several HCC cell lines. Additionally, using Kaplan–Meier plots, the potential prognostic value of miR-211-5p in HCC was analyzed. Cell counting kit-8 (CCK-8) and transwell assays examined the ability of miR-211-5p to induce cell proliferation, migration, and invasion in HCC cultures. The interaction of miR-211-5p and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) was assessed both theoretically and using a luciferase reporter assay. Finally, the ability of miR-211-5p to modulate tumorigenesis in HCC in vivo was assessed after establishing a xenograft model.

Results
qRT-PCR demonstrated that the relative expression of miR-211-5p was considerably down-regulated in HCC tissues and cell lines compared with normal tissue. Kaplan–Meier plots indicated that HCC patients with decreased expression of miR-211-5p had poor overall survival. Upregulation of miR-211-5p in vitro consistently suppressed cell proliferation, migration, and invasion. In contrast, enhanced expression of ACSL4 promoted a malignant phenotype in HCC cells. Importantly, we discovered that ACSL4 was a direct downstream target of miR-211-5p in HCC, and that miR-211-5p suppressed the malignant phenotype by inhibition of ACSL4 expression. Furthermore, miR-211-5p overexpression impaired tumorigenesis and growth of HCC in vivo.

Conclusions
Targeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and represents a promising approach to future therapy of HCC patients.
Rh-relaxin-2 attenuates degranulation of mast cells by inhibiting NF-κB through PI3K-AKT/TNFAIP3 pathway in an experimental germinal matrix hemorrhage rat model
Authors: Li Peng , Zhao Gang , Chen Fanfan , Ding Yan , Wang Tianyi , Liu Shengpeng , Lu Weitian , Xu Weilin , Flores Jerry , Ocak Umut , Zhang Tongyu , Zhang John H. , Tang Jiping 
Published: August 2020

Abstract
Background
Mast cells play an important role in early immune reactions in the brain by degranulation and the consequent inflammatory response. Our aim of the study is to investigate the effects of rh-relaxin-2 on mast cells and the underlying mechanisms in a germinal matrix hemorrhage (GMH) rat model.

Methods
One hundred seventy-three P7 rat pups were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Clodronate liposome was administered through intracerebroventricular (i.c.v.) injections 24 h prior to GMH to inhibit microglia. Rh-relaxin-2 was administered intraperitoneally at 1 h and 13 h after GMH. Small interfering RNA of RXFP1 and PI3K inhibitor LY294002 were given by i.c.v. injection. Post-GMH evaluation included neurobehavioral function, Western blot analysis, immunofluorescence, Nissl staining, and toluidine blue staining.

Results
Our results demonstrated that endogenous relaxin-2 was downregulated and that RXFP1 level peaked on the first day after GMH. Administration of rh-relaxin-2 improved neurological functions, attenuated degranulation of mast cells and neuroinflammation, and ameliorated post-hemorrhagic hydrocephalus (PHH) after GMH. These effects were associated with RXFP1 activation, increased expression of PI3K, phosphorylated AKT and TNFAIP3, and decreased levels of phosphorylated NF-κB, tryptase, chymase, IL-6, and TNF-α. However, knockdown of RXFP1 and PI3K inhibition abolished the protective effects of rh-relaxin-2.

Conclusions
Our findings showed that rh-relaxin-2 attenuated degranulation of mast cells and neuroinflammation, improved neurological outcomes, and ameliorated hydrocephalus after GMH through RXFP1/PI3K-AKT/TNFAIP3/NF-κB signaling pathway.
Transgenic inhibition of astroglial NF-κB restrains the neuroinflammatory and neurodegenerative outcomes of experimental mouse glaucoma
Authors: Yang Xiangjun , Zeng Qun , Barış Mine , Tezel Gülgün 
Published: August 2020

AbstractBackgroundGlia-driven neuroinflammation promotes neuron injury in glaucoma that is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness. Although therapeutic modulation of neuroinflammation is increasingly viewed as a logical strategy to avoid inflammatory neurotoxicity in glaucoma, current understanding of the molecular regulation of neuroinflammation is incomplete, and the molecular targets for immunomodulation remains unknown. Growing datasets pointed to nuclear factor-kappaB (NF-κB), a key transcriptional activator of inflammation, which was identified to be most affected in glaucomatous astroglia. Using a cell type-specific experimental approach, this study aimed to determine the value of astroglial NF-κB as a potential treatment target for immunomodulation in experimental mouse glaucoma.MethodsNeuroinflammatory and neurodegenerative outcomes of experimental glaucoma were comparatively analyzed in mice with or without cre/lox-based conditional deletion of astroglialIκKβ, which is the main activating kinase involved in IκB degradation through the canonical pathway of NF-κB activation. Glial responses and the inflammatory status of the retina and optic nerve were analyzed by cell morphology and cytokine profiling, and neuron structure and function were analyzed by counting retinal ganglion cell (RGC) axons and somas and recording pattern electroretinography (PERG) responses.ResultsAnalysis of glial inflammatory responses showed immunomodulatory outcomes of the conditional transgenic deletion ofIκKβin astroglia. Various pro-inflammatory cytokines known to be transcriptional targets for NF-κB exhibited decreased production inIκKβ-deleted astroglia, which included TNF-α that can induce RGC apoptosis and axon degeneration during glaucomatous neurodegeneration. Indeed, transgenic modulation of inflammatory responses by astroglialIκKβdeletion reduced neurodegeneration at different neuronal compartments, including both RGC axons and somas, and protected PERG responses.ConclusionsThe findings of this study support a key role for astroglial NF-κB in neuroinflammatory and neurodegenerative outcomes of experimental glaucoma and the potential of this transcriptional regulator pathway as a glial treatment target to provide neuroprotection through immunomodulation. By pointing to a potential treatment strategy targeting the astroglia, these experimental findings are promising for future clinical translation through transgenic applications to improve the treatment of this blinding disease.
Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury
Authors: Jiao Mengya , Li Xiangyong , Chen Liying , Wang Xiaodi , Yuan Baohong , Liu Tao , Dong Qun , Mei Hanfang , Yin Hui 
Published: August 2020

AbstractBackgroundInterleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action.MethodsThe brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia and treated with IL-33 at a dose of 0.2 μg/day i.p. for 3 days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells and cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes.ResultsThe expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 days after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation.ConclusionsThe activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.