bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-33 genetics and epigenetics in immune-related diseases
Authors: Di Salvo Eleonora , Casciaro Marco , Gangemi Sebastiano 
Published: September 2021

AbstractInterleukin-33 (IL-33) is a 30KDa protein, which belongs to the Interleukin-1 cytokine family. It is a crucial regulator of innate and adaptive immune responses. This interleukin is additionally involved in the inflammatory reaction versus helminthic infections. Interleukin 33 acts on group 2 innate lymphoid cells and mast cells macrophages, dendritic cells and CD4 + Th2 cells eliciting a type 2 immune response. Moreover, the cytokine can activate the ST2 of Tregs, demonstrating its ability to downregulate inflammation. IL-33 has also an intracellular function by regulating transcription. The active IL-33 doesn’t have a signal peptide, so it’s not released across a normal secretory pathway; the interleukin is released when the cells are damages and acts like an “alarmin”. Its influence on immune activation could be slightly adjusted via fine epigenetic interactions involving cascade pathways and immune genes. Due to the diverse data emerged from different experimental research, we decided span literature to clarify, as much as possible, how IL-33 is influenced by and influence gene expression. The authors reported how its balance is influenced, according to the tissue considered. Fundamental for immune-related diseases, IL-33 has a key role in controlling inflammation. The understanding of the cytokine switch will be fundamental in a near future in order to block or activate some immune pathways. In fact, we could control interleukins effects not only by monoclonal antibodies but also by using siRNA or miRNAs for silencing or expressing key genes.
Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin
Authors: Li Jie , Zeng Huamin , You Yu , Wang Rongrong , Tan Tiantian , Wang Weiming , Yin Liyan , Zeng Zhaowu , Zeng Yiying , Xie Tian 
Published: September 2021

Abstract
Background
Effective treatment of glioma requires a nanocarrier that can cross the blood–brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma.

Results
The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution.

Conclusion
These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

Graphic Abstract
Health-related quality of life in men and women who experienced cardiovascular diseases: Tehran Lipid and Glucose Study
Authors: Jalali-Farahani Sara , Amiri Parisa , Fakhredin Hanieh , Torshizi Kiana , Cheraghi Leila , Khalili Davood , Azizi Fereidoun 
Published: September 2021

Abstract
Background
Cardiovascular diseases (CVDs) are among the most common causes of death worldwide, including in Iran. Considering the adverse effects of CVDs on physical and psychosocial health; this study aims to investigate the association between experience of CVDs and health-related quality of life (HRQoL) in adult participants of the Tehran Lipid and Glucose Study (TLGS).

Methods
The participants of this cross-sectional study were 7009 adults (≥ 20 years) who participated in the TLGS during 2014–2017. Demographic information and HRQoL data was collected through validated questionnaires by trained interviewers. HRQoL was assessed by the Iranian version of the SF-12 questionnaire. Data was analyzed using the SPSS software.

Results
The mean age of participants was 46.8 ± 14.6 years and 46.1% of them were men. A total of 9.0% of men and 4.4% of women had CVDs. In men, the mean physical HRQoL summary score was significantly lower in those with CVDs compared to those without CVDs (46.6 ± 0.8 vs. 48.5 ± 0.7, p > 0.001). In women, the mean mental HRQoL summary scores was significantly lower in those with CVDs compared to those without CVDs (42.8 ± 1.0 vs. 45.2 ± 0.5, p = 0.009). In adjusted models, men with CVDs were more likely to report poor physical HRQoL compared to men without CVDs (OR(95%CI): 1.93(1.32–2.84), p = 0.001); whereas for women, the chance of reporting poor mental HRQoL was 68% higher in those with CVDs than those without CVDs (OR(95%CI): 1.68(1.11–2.54), p = 0.015).

Conclusion
The findings of the current study indicate poorer HRQoL in those who experienced CVDs compared to their healthy counterparts with a sex specific pattern. While for men, CVDs were associated with more significant impairment in the physical dimension of HRQoL, women experienced a similar impairment in the mental dimension of HRQoL.
Frontline healthcare workers’ mental distress, top concerns, and assessment on hierarchy of controls in response to COVID-19: a cross-sectional survey study
Authors: Zhang Lingling , Flike Kimberlee L. , Gakumo C. Ann , Shi Ling , Leveille Suzanne G. , Thompson Linda S. 
Published: September 2021

Abstract
Background
The existing studies showed that frontline healthcare workers during an epidemic experienced unusual stressors and mental distress which even lasted for years after the crisis. It is important to learn about their concerns early to mitigate the negative impact as well as to evaluate disease control from experiences on the front lines for improving responses to the outbreak. The study aimed to provide insights on how to strengthen public health responses to protect healthcare workers both physically and mentally, and effectively control the disease in light of hierarchy of controls.

Methods
A cross-sectional survey was distributed online via Qualtrics to frontline healthcare workers during the COVID-19 through a university’s nursing program and received 267 valid responses from 103 certificated nursing assistants, 125 nurses, and 39 other health professionals. A descriptive data analysis with a Chi-square test at a two-sided 0.05 level of significance was performed on factors that potentially affected mental health of healthcare workers and effectiveness of disease control at workplace in five domains. The themes were summarized on open-ended questions.

Results
About 30% of the respondents showed the symptom of depression and needed a further investigation. The influencing factors in five domains were examined. Engineering and administrative controls, as well as PPE were widely used in response to COVID-19. The respondents assessed the state and workplace responses to COVID-19 better than the federal government responses. The workplace responses were considered most effective. Multiple factors with a statistically significant correlation with effectiveness of the disease control at workplace were identified.

Conclusions
The study suggested that timely responses at policy level will be more effective than other measures in early prevention and control of the pandemic, mental distress should be addressed in addition to PPE, and nursing programs should consider providing a situation-specific career coaching or counseling for students. A longitudinal study at a larger scale is warranted to capture the variation of time change with the disease control evolvement and across geographic regions.
Gene clusters based on OLIG2 and CD276 could distinguish molecular profiling in glioblastoma
Authors: Fu Minjie , Zhang Jinsen , Li Weifeng , He Shan , Zhang Jingwen , Tennant Daniel , Hua Wei , Mao Ying 
Published: September 2021

Abstract
Background
The molecular profiling of glioblastoma (GBM) based on transcriptomic analysis could provide precise treatment and prognosis. However, current subtyping (classic, mesenchymal, neural, proneural) is time-consuming and cost-intensive hindering its clinical application. A simple and efficient method for classification was imperative.

Methods
In this study, to simplify GBM subtyping more efficiently, we applied a random forest algorithm to conduct 26 genes as a cluster featured with hub genes, OLIG2 and CD276. Functional enrichment analysis and Protein–protein interaction were performed using the genes in this gene cluster. The classification efficiency of the gene cluster was validated by WGCNA and LASSO algorithms, and tested in GSE84010 and Gravandeel’s GBM datasets.

Results
The gene cluster (n = 26) could distinguish mesenchymal and proneural excellently (AUC = 0.92), which could be validated by multiple algorithms (WGCNA, LASSO) and datasets (GSE84010 and Gravandeel’s GBM dataset). The gene cluster could be functionally enriched in DNA elements and T cell associated pathways. Additionally, five genes in the signature could predict the prognosis well (p = 0.0051 for training cohort, p = 0.065 for test cohort).

Conclusions
Our study proved the accuracy and efficiency of random forest classifier for GBM subtyping, which could provide a convenient and efficient method for subtyping Proneural and Mesenchymal GBM.
Role of galectin 3 binding protein in cancer progression: a potential novel therapeutic target
Authors: Capone Emily , Iacobelli Stefano , Sala Gianluca 
Published: September 2021

AbstractThe lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is a secreted, hyperglycosylated protein expressed by the majority of human cells. It was first identified as cancer and metastasis associated protein, while its role in innate immune response upon viral infection remains still to be clarified. Since its discovery dated in early 90 s, a large body of literature has been accumulating highlighting both a prognostic and functional role for LGALS3BP in cancer. Moreover, data from our group and other have strongly suggested that this protein is enriched in cancer-associated extracellular vesicles and may be considered a promising candidate for a targeted therapy in LGALS3BP positive cancers. Here, we extensively reviewed the literature relative to LGALS3BP role in cancer and its potential value as a therapeutic target.
Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer
Authors: Espedal Heidi , Berg Hege F. , Fonnes Tina , Fasmer Kristine E. , Krakstad Camilla , Haldorsen Ingfrid S. 
Published: September 2021

Abstract
Background
Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibility and utility of MRI and dynamic 18F-fluorodeoxyglucose (FDG)-PET imaging for monitoring tumor progression and assessing chemotherapy response in an orthotopic organoid-based patient-derived xenograft (O-PDX) mouse model of EC.

Methods
18 O-PDX mice (grade 3 endometrioid EC, stage IIIC1), selectively underwent weekly T2-weighted MRI (total scans = 32), diffusion-weighted MRI (DWI) (total scans = 9) and dynamic 18F-FDG-PET (total scans = 26) during tumor progression. MRI tumor volumes (vMRI), tumor apparent diffusion coefficient values (ADCmean) and metabolic tumor parameters from 18F-FDG-PET including maximum and mean standard uptake values (SUVmax/SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic rate of 18F-FDG (MRFDG) were calculated. Further, nine mice were included in a chemotherapy treatment study (treatment; n = 5, controls; n = 4) and tumor ADCmean-values were compared to changes in vMRI and cellular density from histology at endpoint. A Mann–Whitney test was used to evaluate differences between groups.

Results
Tumors with large tumor volumes (vMRI) had higher metabolic activity (MTV and TLG) in a clear linear relationship (r2 = 0.92 and 0.89, respectively). Non-invasive calculation of MRFDG from dynamic 18F-FDG-PET (mean MRFDG = 0.39 μmol/min) was feasible using an image-derived input function. Treated mice had higher tumor ADCmean (p = 0.03), lower vMRI (p = 0.03) and tumor cellular density (p = 0.02) than non-treated mice, all indicating treatment response.

Conclusion
Preclinical imaging mirroring clinical imaging methods in EC is highly feasible for monitoring tumor progression and treatment response in the present orthotopic organoid mouse model.
Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice
Authors: Papazian Irini , Tsoukala Eleni , Boutou Athena , Karamita Maria , Kambas Konstantinos , Iliopoulou Lida , Fischer Roman , Kontermann Roland E. , Denis Maria C. , Kollias George , Lassmann Hans , Probert Lesley 
Published: September 2021

Abstract
Background
During inflammatory demyelination, TNF receptor 1 (TNFR1) mediates detrimental proinflammatory effects of soluble TNF (solTNF), whereas TNFR2 mediates beneficial effects of transmembrane TNF (tmTNF) through oligodendroglia, microglia, and possibly other cell types. This model supports the use of selective inhibitors of solTNF/TNFR1 as anti-inflammatory drugs for central nervous system (CNS) diseases. A potential obstacle is the neuroprotective effect of solTNF pretreatment described in cultured neurons, but the relevance in vivo is unknown.

Methods
To address this question, we generated mice with neuron-specific depletion of TNFR1, TNFR2, or inhibitor of NF-κB kinase subunit β (IKKβ), a main downstream mediator of TNFR signaling, and applied experimental models of inflammatory demyelination and acute and preconditioning glutamate excitotoxicity. We also investigated the molecular and cellular requirements of solTNF neuroprotection by generating astrocyte-neuron co-cultures with different combinations of wild-type (WT) and TNF and TNFR knockout cells and measuring N-methyl-d-aspartate (NMDA) excitotoxicity in vitro.

Results
Neither neuronal TNFR1 nor TNFR2 protected mice during inflammatory demyelination. In fact, both neuronal TNFR1 and neuronal IKKβ promoted microglial responses and tissue injury, and TNFR1 was further required for oligodendrocyte loss and axonal damage in cuprizone-induced demyelination. In contrast, neuronal TNFR2 increased preconditioning protection in a kainic acid (KA) excitotoxicity model in mice and limited hippocampal neuron death. The protective effects of neuronal TNFR2 observed in vivo were further investigated in vitro. As previously described, pretreatment of astrocyte-neuron co-cultures with solTNF (and therefore TNFR1) protected them against NMDA excitotoxicity. However, protection was dependent on astrocyte, not neuronal TNFR1, on astrocyte tmTNF-neuronal TNFR2 interactions, and was reproduced by a TNFR2 agonist.

Conclusions
These results demonstrate that neuronal TNF receptors perform fundamentally different roles in CNS pathology in vivo, with neuronal TNFR1 and IKKβ promoting microglial inflammation and neurotoxicity in demyelination, and neuronal TNFR2 mediating neuroprotection in excitotoxicity. They also reveal that previously described neuroprotective effects of solTNF against glutamate excitotoxicity in vitro are indirect and mediated via astrocyte tmTNF-neuron TNFR2 interactions. These results consolidate the concept that selective inhibition of solTNF/TNFR1 with maintenance of TNFR2 function would have combined anti-inflammatory and neuroprotective properties required for safe treatment of CNS diseases.
Arginyl-tRNA-protein transferase 1 contributes to governing optimal stability of the human immunodeficiency virus type 1 core
Authors: Kishimoto Naoki , Okano Ryosuke , Akita Ayano , Miura Satoshi , Irie Ayaka , Takamune Nobutoki , Misumi Shogo 
Published: September 2021

Abstract
Background
The genome of human immunodeficiency virus type 1 (HIV-1) is encapsulated in a core consisting of viral capsid proteins (CA). After viral entry, the HIV-1 core dissociates and releases the viral genome into the target cell, this process is called uncoating. Uncoating of HIV-1 core is one of the critical events in viral replication and several studies show that host proteins positively or negatively regulate this process by interacting directly with the HIV-1 CA.

Results
Here, we show that arginyl-tRNA-protein transferase 1 (ATE1) plays an important role in the uncoating process by governing the optimal core stability. Yeast two-hybrid screening of a human cDNA library identified ATE1 as an HIV-1-CA-interacting protein and direct interaction of ATE1 with Pr55gag and p160gag − pol via HIV-1 CA was observed by cell-based pull-down assay. ATE1 knockdown in HIV-1 producer cells resulted in the production of less infectious viruses, which have normal amounts of the early products of the reverse transcription reaction but reduced amounts of the late products of the reverse transcription. Interestingly, ATE1 overexpression in HIV-1 producer cells also resulted in the production of poor infectious viruses. Cell-based fate-of-capsid assay, a commonly used method for evaluating uncoating by measuring core stability, showed that the amounts of pelletable cores in cells infected with the virus produced from ATE1-knockdown cells increased compared with those detected in the cells infected with the control virus. In contrast, the amounts of pelletable cores in cells infected with the virus produced from ATE1-overexpressing cells decreased compared with those detected in the cells infected with the control virus.

Conclusions
These results indicate that ATE1 expression levels in HIV-1 producer cells contribute to the adequate formation of a stable HIV-1 core. These findings provide insights into a novel mechanism of HIV-1 uncoating and revealed ATE1 as a new host factor regulating HIV-1 replication.

Graphic abstract
Family planning for women with severe mental illness in rural Ethiopia: a qualitative study
Authors: Zerihun Tigist , Sorsdahl Katherine , Hanlon Charlotte 
Published: September 2021

Abstract
Background
Family planning is a crucial issue for all women of reproductive age, but in women with severe mental illness (SMI), there may be particular challenges and concerns. As primary care-based mental health services are expanding in low- and middle-income countries (LMICs), there is an opportunity to improve family planning services for women with SMI. However, research exploring unmet family planning needs of women with SMI in such settings is scarce. Therefore, the present study explored the family planning experiences and preferences of women with SMI who reside in a predominantly rural area of Ethiopia.

Methods
A qualitative study was conducted. Women with SMI who were participating in the ongoing population-based cohort study in Butajira were selected purposively based on their responses to a quantitative survey of current family planning utilisation. In-depth interviews were conducted with 16 women with SMI who were of reproductive age. Audio files were transcribed in Amharic, translated into English and analysed thematically.

Results
Participants reported pervasive effects of SMI upon the intimate relationships and sexual lives of women. Although women with SMI felt that family planning was important, they had limited knowledge of family planning generally, and a lack of understanding of the specific family planning needs relevant to having SMI. None of the women with SMI in the present study had received any recommendations to use family planning services while accessing mental health care services. The participants identified ways in which primary care-based mental health services could better meet their family planning needs.

Conclusions
This study provided in-depth perspectives from women with SMI about the broader context of their family planning experience, needs, barriers and how integrated primary care services could better meet their needs. Empowerment of women with SMI to access information and services needs to be an important focus of future efforts to improve the reproductive experiences of this vulnerable group.
Revealing the coexistence of differentiation and communication in an endemic hare, Lepus yarkandensis (Mammalia, Leporidae) using specific-length amplified fragment sequencing
Authors: Ababaikeri Buweihailiqiemu , Zhang Yucong , Dai Huiying , Shan Wenjuan 
Published: September 2021

Abstract
Background
The Yarkand hare (Lepus yarkandensis Günther, 1875) is endemic to oasis and desert areas around the Tarim Basin in the Xinjiang Uyghur Autonomous Region of northwest China; however, genome-wide information for this species remains limited. Moreover, the genetic variation, genetic structure, and phylogenetic relationships of Yarkand hare from the plateau mountain regions have not been reported. Thus, we used specific-length amplified fragment sequencing (SLAF-seq) technology to evaluate the genetic diversity of 76 Yarkand hares from seven geographic populations in the northern and southwestern parts of the Tarim Basin to investigate single-nucleotide polymorphism (SNP) marker-based population differentiation and evolutionary processes. Selective sweep analysis was conducted to identify genetic differences between populations.

Results
Using SLAF-seq, a total of 1,835,504 SNPs were initially obtained, of which 308,942 high-confidence SNPs were selected for further analysis. Yarkand hares exhibited a relatively high degree of genetic diversity at the SNP level. Based on pairwise FST estimates, the north and southwest groups showed a moderate level of genetic differentiation. Phylogenetic tree and population structure analyses demonstrated evident systematic phylogeographical structure patterns consistent with the geographical distribution of the hares. Hierarchical analysis of molecular variation further indicated that genetic variation was mainly observed within populations. Low to moderate genetic differentiation also occurred among populations despite a common genomic background, likely due to geographical barriers, genetic drift, and differential selection pressure of distinct environments. Nevertheless, the observed lineage-mixing pattern, as indicated by the evolutionary tree, principal component analysis, population structure, and TreeMix analyses, suggests a certain degree of gene flow between the north and southwest groups. This may be related to the migration of hares to high-altitude water sources southwest of the basin during glacial climatic oscillations, as well as river re-diffusion and oasis restoration in the basin following the glacial period. We also identified candidate genes, and their associated gene ontology terms and pathways, related to the adaptation of Yarkand hares to different environmental habitats.

Conclusions
The identified genome-wide SNPs, genetic diversity, and population structure of Yarkand hares expand our understanding of the genetic background of this endemic species and provide valuable insights into its environmental adaptation, allowing for further exploration of the underlying mechanisms.