bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas
Authors: Wang Peng , Zhang Jingjing , He Shuai , Xiao Boan , Peng Xiaobin
Published: November 2020

Background

Gliomas are one of the most common primary tumors of the central nervous system, and have an unfavorable prognosis. SLC39A1 is a zinc ion transport protein which inhibits the progression of prostate cancer. By studying the role and mechanism of SLC39A1 in the progression of gliomas, perhaps a new therapeutic target can be provided for their treatment.

Method

The TCGA, CCGA, GSE16011, GSE44971 and GSE11260 data sets were employed to evaluate the expression level of SLC39A1 in paracancerous and glioma tissues. In addition, Kaplan–Meier analysis, Cox analysis, and the ESTIMATE and CIBERSORT algorithms were used to analyze its prognostic value and immune infiltration correlation. A CCK-8 and flow cytometer were used to measure the effects of SLC39A1 on U87 cell proliferation or apoptosis; RT-qPCR and western blot were used to detect its effects on the expression of MMP2\MMP9.

Results

SLC39A1 has up-regulated expression in glioma tissues. High SLC39A1 expression predicted significantly worse survival. Univariate and multivariate analysis show that SLC39A1 independently indicated poor prognosis in patients with gliomas. The expression of SLC39A1 is significantly correlated with clinical pathological parameters such as Grade, IDH mutation status, and 1p19q codeletion status. In vitro experimental results show that SLC39A1 promotes proliferation of glioma cells, inhibits their apoptosis, and promotes expression of MMP2\MMP9. In addition, it may affect infiltration of immune cells into the glioma microenvironment.

Conclusion

SLC39A1 may serve as a new prognostic biomarker and potential target for treatment of gliomas.
Can computed tomography-based radiomics potentially discriminate between anterior mediastinal cysts and type B1 and B2 thymomas?
Authors: Liu Lulu , Lu Fangxiao , Pang Peipei , Shao Guoliang
Published: November 2020

Background

Anterior mediastinal cysts (AMC) are often misdiagnosed as thymomas and undergo surgical resection, which caused unnecessary treatment and medical resource waste. The purpose of this study is to explore potential possibility of computed tomography (CT)-based radiomics for the diagnosis of AMC and type B1 and B2 thymomas.

Methods

A group of 188 patients with pathologically confirmed AMC (106 cases misdiagnosed as thymomas in CT) and thymomas (82 cases) and underwent routine chest CT from January 2010 to December 2018 were retrospectively analyzed. The lesions were manually delineated using ITK-SNAP software, and radiomics features were performed using the artificial intelligence kit (AK) software. A total of 180 tumour texture features were extracted from enhanced CT and unenhanced CT, respectively. The general test, correlation analysis, and LASSO were used to features selection and then the radiomics signature (radscore) was obtained. The combined model including radscore and independent clinical factors was developed. The model performances were evaluated on discrimination, calibration curve.

Results

Two radscore models were constructed from the unenhanced and enhanced phases based on the selected four and three features, respectively. The AUC, sensitivity, and specificity of the enhanced radscore model were 0.928, 89.3%, and 83.8% in the training dataset and 0.899, 84.6%, and 87.5% in the test dataset (higher than the unenhanced radscore model). The combined model of enhanced CT including radiomics features and independent clinical factors yielded an AUC, sensitivity and specificity of 0.941, 82.1%, and 94.6% in the training dataset and 0.938, 92.3%, and 87.5% in the test dataset (higher than the unenhanced combined model and enhanced radscore model).

Conclusions

The study suggested the possibility that the combined model in enhanced CT provided a potential tool to facilitate the differential diagnosis of AMC and type B1 and B2 thymomas.
Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade
Authors: Ding L. , Jidkova S. , Greuter M. J. W. , Van Herck K. , Goossens M. , Martens P. , de Bock G. H. , Van Hal G.
Published: November 2020

Background

Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown.

Objective

To assess the determinants of BC screening coverage in Flanders.

Methods

Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008–2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type.

Results

Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50–54.40%) and 14.10% (IQR: 9.80–19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199–4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455–2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624–0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967–0.972).

Conclusion

Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.
Correction to: LTBP1 plays a potential bridge between depressive disorder and glioblastoma
Authors: Fu Xiaojun , Zhang Pei , Song Hongwang , Wu Chenxing , Li Shengzhen , Li Shouwei , Yan Changxiang
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Immunological classification of gliomas based on immunogenomic profiling
Authors: Feng Qiushi , Li Lin , Li Mengyuan , Wang Xiaosheng
Published: November 2020

Background

Gliomas are heterogeneous in the tumor immune microenvironment (TIM). However, a classification of gliomas based on immunogenomic profiling remains lacking.

Methods

We hierarchically clustered gliomas based on the enrichment levels of 28 immune cells in the TIM in five datasets and obtained three clusters: immunity-high, immunity-medium, and immunity-low.

Results

Glioblastomas were mainly distributed in immunity-high and immunity-medium, while lower-grade gliomas were distributed in all the three subtypes and predominated in immunity-low. Immunity-low displayed a better survival than other subtypes, indicating a negative correlation between immune infiltration and survival prognosis in gliomas.IDHmutations had a negative correlation with glioma immunity. Immunity-high had higher tumor stemness and epithelial-mesenchymal transition scores and included more high-grade tumors than immunity-low, suggesting that elevated immunity is associated with tumor progression in gliomas. Immunity-high had higher tumor mutation burden and more frequent somatic copy number alterations, suggesting a positive association between tumor immunity and genomic instability in gliomas.

Conclusions

The identification of immune-specific glioma subtypes has potential clinical implications for the immunotherapy of gliomas.
CCL3 contributes to secondary damage after spinal cord injury
Authors: Pelisch Nicolas , Rosas Almanza Jose , Stehlik Kyle E. , Aperi Brandy V. , Kroner Antje
Published: November 2020

Background

Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system.

Methods

A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type andCCL3−/−mice.

Results

The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size usingCCL3−/−mice.CCL3−/−mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced inthe absence of CCL3.

Conclusion

We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.
Oleanolic acid ameliorates intestinal alterations associated with EAE
Authors: Gutierrez Beatriz , Gallardo Isabel , Ruiz Lorena , Alvarez Yolanda , Cachofeiro Victoria , Margolles Abelardo , Hernandez Marita , Nieto Maria Luisa
Published: November 2020

Background

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment.

Methods

Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects.

Results

We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract.

Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS.

Conclusion

These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.
Astrocyte-derived clusterin suppresses amyloid formation in vivo
Authors: Wojtas Aleksandra M. , Sens Jonathon P. , Kang Silvia S. , Baker Kelsey E. , Berry Taylor J. , Kurti Aishe , Daughrity Lillian , Jansen-West Karen R. , Dickson Dennis W. , Petrucelli Leonard , Bu Guojun , Liu Chia-Chen , Fryer John D.
Published: November 2020

Background

Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer’s disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the common non-coding, protective CLU variants associated with increased expression. Although there is strong evidence implicating CLU in amyloid metabolism, the exact mechanism underlying the CLU involvement in AD is not fully understood or whether physiologic alterations of CLU levels in the brain would be protective.

Results

We used a gene delivery approach to overexpress CLU in astrocytes, the major source of CLU expression in the brain. We found that CLU overexpression resulted in a significant reduction of total and fibrillar amyloid in both cortex and hippocampus in the APP/PS1 mouse model of AD amyloidosis. CLU overexpression also ameliorated amyloid-associated neurotoxicity and gliosis. To complement these overexpression studies, we also analyzed the effects of haploinsufficiency of Clu using heterozygous (Clu+/−) mice and control littermates in the APP/PS1 model. CLU reduction led to a substantial increase in the amyloid plaque load in both cortex and hippocampus in APP/PS1; Clu+/− mice compared to wild-type (APP/PS1; Clu+/+) littermate controls, with a concomitant increase in neuritic dystrophy and gliosis.

Conclusions

Thus, both physiologic ~ 30% overexpression or ~ 50% reduction in CLU have substantial impacts on amyloid load and associated pathologies. Our results demonstrate that CLU plays a major role in Aβ accumulation in the brain and suggest that efforts aimed at CLU upregulation via pharmacological or gene delivery approaches offer a promising therapeutic strategy to regulate amyloid pathology.
Determinants of postnatal care utilization in sub-Saharan Africa: a meta and multilevel analysis of data from 36 sub-Saharan countries
Authors: Tessema Zemenu Tadesse , Yazachew Lake , Tesema Getayeneh Antehunegn , Teshale Achamyeleh Birhanu
Published: November 2020

Introduction

Globally, over 65% of maternal deaths occur during the first 42 days of postpartum while the same proportion of neonatal deaths occur during the first 7 days of life. In sab- Saharan Africa, 4.7 million mothers, newborns, and children die on annual basis. As to our knowledge, there is no study on postnatal care utilization that incorporates all sub-Saharan Africa countries that had DHS data. Therefore, this study aimed at identifying pooled magnitude and determinants of postnatal care utilization in sub-Saharan Africa.

Method

A population-based cross-sectional study from the most recent Demographic and Health Surveys data from the period of 2006 to 2018 of 36 SSA countries were used. A total weighted sample of 286,255 reproductive-age women who gave birth 5 years preceding the survey were included in the study. A meta-analysis of DHS data of each Sub-Saharan countries was conducted to generate pooled magnitude and a forest plot was used to present it. A multilevel logistic regression model was fitted to identify determinants of postnatal care utilization. The AOR (Adjusted Odds Ratio) with their 95% CI and p-value ≤0.05 was used to declare that determinates associated with postnatal care utilization.

Result

The pooled magnitude of postnatal care utilization in sub-Saharan Africa countries was 52.48% [95% CI: 52.33, 52.63], with the highest postnatal care utilization in the Central Region of Africa (73.51%) and the low postnatal care utilization in Eastern Regions of Africa (31.71%). In the multilevel logistic regression model region, residence, age group, maternal education, maternal occupation, media exposure, ANC visit, place of delivery, and accessing health care were determinants of postnatal care utilization in Sub-Saharan Africa.

Conclusion

The coverage of postnatal care service utilization was low with high disparities among the region. Being in rural residence, young age group, low education level, had no occupation, not exposed to media, a big problem to access health care, not had ANC visit, and home delivery was associated with low postnatal care service utilization. This study evidenced that there is a wide gap in postnatal care utilization between SSA countries. Special attention is required to improve health accessibility, utilization, and quality of maternal health services to increase postnatal care service utilization in the region.
Designing process evaluations using case study to explore the context of complex interventions evaluated in trials
Authors: Grant Aileen , Bugge Carol , Wells Mary
Published: November 2020

Background

Process evaluations are an important component of an effectiveness evaluation as they focus on understanding the relationship between interventions and context to explain how and why interventions work or fail, and whether they can be transferred to other settings and populations. However, historically, context has not been sufficiently explored and reported resulting in the poor uptake of trial results. Therefore, suitable methodologies are needed to guide the investigation of context. Case study is one appropriate methodology, but there is little guidance about what case study design can offer the study of context in trials. We address this gap in the literature by presenting a number of important considerations for process evaluation using a case study design.

Main text

In this paper, we define context, the relationship between complex interventions and context, and describe case study design methodology. A well-designed process evaluation using case study should consider the following core components: the purpose; definition of the intervention; the trial design, the case, the theories or logic models underpinning the intervention, the sampling approach and the conceptual or theoretical framework. We describe each of these in detail and highlight with examples from recently published process evaluations.

Conclusions

There are a number of approaches to process evaluation design in the literature; however, there is a paucity of research on what case study design can offer process evaluations. We argue that case study is one of the best research designs to underpin process evaluations, to capture the dynamic and complex relationship between intervention and context during implementation. We provide a comprehensive overview of the issues for process evaluation design to consider when using a case study design.

Trial registration

DQIP - ClinicalTrials.gov number,NCT01425502- OPAL -ISRCTN57746448
Population genomics and antimicrobial resistance in Corynebacterium diphtheriae
Authors: Hennart Melanie , Panunzi Leonardo G. , Rodrigues Carla , Gaday Quentin , Baines Sarah L. , Barros-Pinkelnig Marina , Carmi-Leroy Annick , Dazas Melody , Wehenkel Anne Marie , Didelot Xavier , Toubiana Julie , Badell Edgar , Brisse Sylvain
Published: November 2020

Background

Corynebacterium diphtheriae, the agent of diphtheria, is a genetically diverse bacterial species. Although antimicrobial resistance has emerged against several drugs including first-line penicillin, the genomic determinants and population dynamics of resistance are largely unknown for this neglected human pathogen.

Methods

Here, we analyzed the associations of antimicrobial susceptibility phenotypes, diphtheria toxin production, and genomic features inC. diphtheriae. We used 247 strains collected over several decades in multiple world regions, including the 163 clinical isolates collected prospectively from 2008 to 2017 in France mainland and overseas territories.

Results

Phylogenetic analysis revealed multiple deep-branching sublineages, grouped into a Mitis lineage strongly associated with diphtheria toxin production and a largely toxin gene-negative Gravis lineage with few toxin-producing isolates including the 1990s ex-Soviet Union outbreak strain. The distribution of susceptibility phenotypes allowed proposing ecological cutoffs for most of the 19 agents tested, thereby defining acquired antimicrobial resistance. Penicillin resistance was found in 17.2% of prospective isolates. Seventeen (10.4%) prospective isolates were multidrug-resistant (≥ 3 antimicrobial categories), including four isolates resistant to penicillin and macrolides. Homologous recombination was frequent (r/m = 5), and horizontal gene transfer contributed to the emergence of antimicrobial resistance in multiple sublineages. Genome-wide association mapping uncovered genetic factors of resistance, including an accessory penicillin-binding protein (PBP2m) located in diverse genomic contexts. Genepbp2mis widespread in otherCorynebacteriumspecies, and its expression inC. glutamicumdemonstrated its effect against several beta-lactams. A novel 73-kbC. diphtheriaemultiresistance plasmid was discovered.

Conclusions

This work uncovers the dynamics of antimicrobial resistance inC. diphtheriaein the context of phylogenetic structure, biovar, and diphtheria toxin production and provides a blueprint to analyze re-emerging diphtheria.
Obesity with radiological changes or depression was associated with worse knee outcome in general population: a cluster analysis in the Nagahama study
Authors:   on behalf of the Nagahama Study group, Nigoro Kazuya , Ito Hiromu , Kawata Tomotoshi , Nishitani Kohei , Tabara Yasuharu , Matsuda Fumihiko , Narumiya Shu , Matsuda Shuichi
Published: November 2020

Background

In knee osteoarthritis (OA), pain is the most frequent and dominant symptom. However, which factors other than radiological changes contribute to the symptoms is unresolved. The aims of this study were to identify factors affecting knee pain from various variables with radiological changes taken into count and exploratively examine what subgroups or phenotype could be identified by cluster analysis using the identified knee pain factors.

Methods

Patients 60 years or older who underwent radiographic evaluation were included in this cross-sectional study, and those subjects who completed a questionnaire about knee symptoms without missing data were eligible for analysis. Multiple regression analysis was used to examine the associations between selected variables and The Japanese Knee Osteoarthritis Measure (JKOM) pain score. We grouped the subjects by cluster analysis using identified variables.

Results

Two thousand five hundred forty-two subjects were included in the full set of analyses. Age, body mass index (BMI), radiological grade, bone mineral density (BMD), and high-sensitivity C-reactive protein (hs-CRP) showed a statistically significant correlation with radiological showing the strongest value. For dichotomous variable, presence of depression showed a statistically significant result. We used BMI, radiological grade, BMD, hs-CRP, and presence of depression as a variable for cluster analysis and identified six subgroups: (1) minimal joint disease subgroup, (2) male and high BMD subgroup, (3) high CRP subgroup, (4) severe radiological OA subgroup, (5) depressive subgroup, and (6) moderate radiological OA with high BMI subgroup, showing the worst knee outcome.

Conclusion

This study identified the factors affecting knee pain other than radiological changes and identified six subgroups of knee outcome in the general population. The results showed that obesity with radiological changes or depression was associated with worse knee outcome.
Effects of preoperative low-intensity training with slow movement on early quadriceps weakness after total knee arthroplasty in patients with knee osteoarthritis: a retrospective propensity score-matched study
Authors: Kubo Yusuke , Sugiyama Shuhei , Takachu Rie , Sugiura Takeshi , Sawada Masahiro , Kobori Kaori , Kobori Makoto
Published: November 2020

Background

Severe and early quadriceps weakness (QW) after total knee arthroplasty (TKA), which is caused by acute inflammation resulting from surgical trauma and tourniquet-induced ischemia-reperfusion (IR) injury, can be especially problematic. We focused on tourniquet-induced IR injury, because it has been shown to be preventable through ischemic and exercise preconditioning. Low-intensity resistance exercise with slow movement and tonic force generation (LST) share some similarities with ischemic and exercise preconditioning. The present study primarily aimed to clarify the efficacy of preoperative LST program as prehabilitation for early QW among patients with TKA using propensity score matching analysis.

Methods

This single-center retrospective observational study used data from patients with knee osteoarthritis (n = 277) who were scheduled to undergo unilateral TKA between August 2015 and January 2017. Those with missing outcome data due to their inability to perform tests were excluded. The LST group included participants who performed LST and aerobic exercise (LST session) more than seven times for three months prior to surgery. The control group included participants who performed less than eight LST sessions, a general and light exercise or had no exercise for three months prior to surgery. Knee circumference, thigh volume, knee pain during quadriceps strength test (QST) and timed up and go test (TUG), quadriceps strength, and TUG were measured before and 4 days after surgery. Knee swelling, thigh swelling, Δknee pain, QW, and ΔTUG were determined by comparing pre- and postoperative measurements.

Results

Propensity score matching generated 41 matched pairs who had nearly balanced characteristics. The LST group had a significantly lower knee and thigh swelling, QW, and ΔTUG compared to the control group (all, p < 0.05). No significant differences in Δknee pain during the QST and TUG were observed between both groups (both, p > 0.05).

Conclusions

The present study demonstrated the beneficial effects of preoperative LST program on knee swelling, thigh swelling, QW, and walking disability immediately after TKA.
Peer review practices by medical imaging journals
Authors: Kwee Thomas C. , Adams Hugo J. A. , Kwee Robert M.
Published: November 2020

Objective

To investigate peer review practices by medical imaging journals.

Methods

Journals in the category "radiology, nuclear medicine and medical imaging" of the 2018 Journal Citation Reports were included.

Results

Of 119 included journals, 62 (52.1%) used single-blinded peer review, 49 (41.2%) used double-blinded peer review, two (1.7%) used open peer review and one (0.8%) used both single-blinded and double-blinded peer reviews, while the peer review model of five journals (4.2%) remained unclear. The use of single-blinded peer review was significantly associated with a journal’s impact factor (correlation coefficient of 0.218, P = 0.022). On subgroup analysis, only subspecialty medical imaging journals had a significant association between the use of single-blinded peer review and a journal’s impact factor (correlation coefficient of 0.354, P = 0.025). Forty-eight journals (40.3%) had a reviewer preference option, 48 journals (40.3%) did not have a reviewer recommendation option, and 23 journals (19.3%) obliged authors to indicate reviewers on their manuscript submission systems. Sixty-four journals (53.8%) did not provide an explicit option on their manuscript submission Web site to indicate nonpreferred reviewers, whereas 55 (46.2%) did. There were no significant associations between the option or obligation to indicate preferred or nonpreferred reviewers and a journal’s impact factor.

Conclusion

Single-blinded peer review and the option or obligation to indicate preferred or nonpreferred reviewers are frequently employed by medical imaging journals. Single-blinded review is (weakly) associated with a higher impact factor, also for subspecialty journals. The option or obligation to indicate preferred or nonpreferred reviewers is evenly distributed among journals, regardless of impact factor.
Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells
Authors: Mizuta Yukie , Akahoshi Tomohiko , Guo Jie , Zhang Shuo , Narahara Sayoko , Kawano Takahito , Murata Masaharu , Tokuda Kentaro , Eto Masatoshi , Hashizume Makoto , Yamaura Ken
Published: November 2020

Background

Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage.

Methods

Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection.

Results

The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs.

Conclusion

ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.
Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2 × 2 factorial randomized placebo-controlled trial
Authors: Min Kyunghoon , Suh Mi Ri , Cho Kye Hee , Park Wookyung , Kang Myung Seo , Jang Su Jin , Kim Sang Heum , Rhie Seonkyeong , Choi Jee In , Kim Hyun-Jin , Cha Kwang Yul , Kim MinYoung
Published: November 2020

Background

Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP.

Methods

Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored.

Results

Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration.

Conclusions

These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects.

Trial registration

ClinicalTrials.gov, NCT01991145, registered 25 November 2013.
Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model
Authors: Kim Jae Yeon , Choi Jong Ho , Jun Ji Hye , Park Sohae , Jung Jieun , Bae Si Hyun , Kim Gi Jin
Published: November 2020

Background

Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model.

Methods

PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 using a nonviral sysyem (2 × 106 cells/animal) were intravenously administered into cirrhotic rats. The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed.

Results

PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p < 0.05). Furthermore, transplantation of PD-MSCsPRL-1 using a nonviral AMAXA system promoted engraftment into injured target liver tissues of a rat BDL cirrhotic model and enhanced the metabolism of mitochondria via increased mtDNA and ATP production, thereby improving therapeutic efficacy.

Conclusions

Our findings will further our understanding of the therapeutic mechanism of enhanced MSCs and provide useful data for the development of next-generation MSC-based cell therapy and therapeutic strategies for regenerative medicine in liver disease.
Research on wireless distributed financial risk data stream mining based on dual privacy protection
Authors: Zhao Yuhao
Published: November 2020

With the advancement of network technology and large-scale computing, distributed data streams have been widely used in the application of financial risk analysis. However, while data mining reveals financial models, it also increasingly poses a threat to privacy. Therefore, how to prevent privacy leakage during the efficient mining process poses new challenges to the data mining technology. This article is mainly aimed at the current privacy data leakage in financial data mining, combined with existing data mining technology to study data mining and privacy protection. First, a data mining model for dual privacy protection is defined, which can better meet the characteristics of distributed data streams while achieving privacy protection effects. Secondly, a privacy-oriented data stream mining algorithm is proposed, which uses random interference technology to effectively protect the original sensitive data. Finally, the analysis and discussion of the algorithm in this paper through simulation experiments show that the algorithm is feasible and effective, and can better adapt to the distributed data flow distribution and dynamic characteristics, while achieving better privacy protection effects, effectively reduced communication load.
A note on generalized q-difference equations for general Al-Salam–Carlitz polynomials
Authors: Cao Jian , Xu Binbin , Arjika Sama
Published: November 2020

In this paper, we deduce the generalizedq-difference equations for general Al-Salam–Carlitz polynomials and generalize Arjika’s recent results (Arjika in J. Differ. Equ. Appl. 26:987–999, 2020). In addition, we obtain transformational identities by the method ofq-difference equation. Moreover, we deduce$U(n+1)$U(n+1)type generating functions and Ramanujan’s integrals involving general Al-Salam–Carlitz polynomials byq-difference equation.
Determinants of stunting among children under 2 years in urban informal settlements in Mumbai, India: evidence from a household census
Authors: Das Sushmita , Chanani Sheila , Shah More Neena , Osrin David , Pantvaidya Shanti , Jayaraman Anuja
Published: November 2020

Background

There is limited evidence on the determinants of childhood stunting across urban India or specifically in slum settlements. This study aims to assess the extent of stunting among children under 2 years of age and examine its determinants in informal settlements of Mumbai.

Methods

Data were collected in 2014–2015 in a post intervention census of a cluster randomized controlled trial to improve the health of women and children. Census covered 40 slum settlements of around 600 households each. A total of 3578 children were included in the study. Mixed effects logistic regression models were used to identify factors associated with stunting.

Results

The prevalence of stunting among children aged 0–23 months was 38%. In the adjusted model, higher maternal education (AOR 0.59; 95% CI 0.42, 0.82), birth interval of at least 2 years (AOR 0.71; 95% CI 0.58, 0.87) and intended conception of the child (AOR 0.80; 95% CI 0.64, 0.99) were associated with lower odds of stunting. Maternal exposure to physical violence (AOR 1.83; 95% CI 1.21, 2.77) was associated with higher odds of being stunted. A child aged 18–23 months had 5.04 times greater odds (95% CI 3.91, 6.5) of being stunted than a child less than 6 months of age. Male child had higher odds of being stunted (AOR 1.33; 95% CI 1.14, 1.54).

Conclusions

Our findings support a multidimensional aetiology for stunting. The results of the study emphasize the importance of women’s status and decision-making power in urban India, along with access to and uptake of family planning and services to provide support for survivors of domestic violence. Ultimately, a multilateral effort is needed to ensure the success of nutrition-specific interventions by focusing on the underlying health and social status of women living in urban slums.

Trial registration

ISRCTN Register:ISRCTN56183183, and Clinical Trials Registry of India: CTRI/2012/09/003004
Determinants of high-risk fertility behavior among reproductive-age women in Ethiopia using the recent Ethiopian Demographic Health Survey: a multilevel analysis
Authors: Tessema Zemenu Tadesse , Tamirat Koku Sisay
Published: November 2020

Background

High-risk fertility behavior is associated with numerous unfavorable child and maternal health outcomes such as chronic undernutrition, anemia, and child mortality. As far as our knowledge goes, there is not much study on determinants of high-risk fertility behavior in Ethiopia. Therefore, this study aimed to assess determinants of high-risk fertility behavior among reproductive-age women in Ethiopia.

Method

The study was based on secondary data analysis from the 2016 Ethiopia Demography and Health Survey. A total of 11,022 women who gave birth 5 years preceding the survey were included in this study. Kid’s Record (KR) dataset was used. The adjusted odds ratio (AOR) with its 95% confidence interval (CI) was calculated for those variables included in the multilevel logistic regression model. P value ≤ 0.05 was employed to declare the statistically significant variables.

Results

More than three-fourths (76.9%) of (95% CI 76.11 to 77.69) reproductive-age women had at least one high-risk fertility behavior. Attended primary and secondary education adjusted odds ratio (AOR) (AOR = 0.71; 95% CI 0.63, 0.80 and AOR = 0.73; 95% CI 0.60, 0.89, respectively), never used contraceptive (AOR = 1.25, 95% CI 1.12, 1.40), unwanted pregnancies (AOR = 1.40, 95% CI 1.23, 1.59), had no ANC visit (AOR = 1.19, 95% CI 1.05, 1.35), rural-dwelling (AOR = 1.26, 95% CI 1.04, 1.51), regions of Ethiopia [Somalia (AOR = 1.70; 95% CI 1.24, 2.32) and Amhara (AOR = 0.72; 95% CI 0.53, 0.96)] were determinants of high-risk fertility behavior.

Conclusion

Education, rural residence, unwanted pregnancies, no antenatal care follow-up, and never used contraceptives were determinants of high-risk fertility behavior. Therefore, increased maternal health services, special intervention for hotspot areas, and giving special attention to rural dweller women were highly recommended.
Correction to: The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention
Authors:   CLEAR survey collaborators, Wong Kitty H. F. , Bosanquet Dave C. , Ambler Graeme K. , Qureshi Mahim I. , Hinchliffe Robert J. , Twine Christopher P.
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
L-type voltage-gated calcium channel agonists mitigate hearing loss and modify ribbon synapse morphology in the zebrafish model of Usher syndrome type 1
Authors: Koleilat Alaa , Dugdale Joseph A. , Christenson Trace A. , Bellah Jeffrey L. , Lambert Aaron M. , Masino Mark A. , Ekker Stephen C. , Schimmenti Lisa A.
Published: November 2020

The mariner (myo7aa−/−) mutant is a zebrafish model for Usher syndrome type 1 (USH1). To further characterize hair cell synaptic elements in myo7aa−/− mutants, we focused on the ribbon synapse and evaluated ultrastructure, number and distribution of immunolabeled ribbons, and postsynaptic densities. By transmission electron microscopy, we determined that myo7aa−/− zebrafish have fewer glutamatergic vesicles tethered to ribbon synapses, yet maintain a comparable ribbon area. In myo7aa−/− hair cells, immunolocalization of Ctbp2 showed fewer ribbon-containing cells in total and an altered distribution of Ctbp2 puncta compared to wild-type hair cells. myo7aa−/− mutants have fewer postsynaptic densities – as assessed by MAGUK immunolabeling – compared to wild-type zebrafish. We quantified the circular swimming behavior of myo7aa−/− mutant fish and measured a greater turning angle (absolute smooth orientation). It has previously been shown that L-type voltage-gated calcium channels are necessary for ribbon localization and occurrence of postsynaptic density; thus, we hypothesized and observed that L-type voltage-gated calcium channel agonists change behavioral and synaptic phenotypes in myo7aa−/− mutants in a drug-specific manner. Our results indicate that treatment with L-type voltage-gated calcium channel agonists alter hair cell synaptic elements and improve behavioral phenotypes of myo7aa−/− mutants. Our data support that L-type voltage-gated calcium channel agonists induce morphological changes at the ribbon synapse – in both the number of tethered vesicles and regarding the distribution of Ctbp2 puncta – shift swimming behavior and improve acoustic startle response.
Ribosome-associated quality control of membrane proteins at the endoplasmic reticulum
Authors: Phillips Ben P. , Miller Elizabeth A.
Published: November 2020

Protein synthesis is an energetically costly, complex and risky process. Aberrant protein biogenesis can result in cellular toxicity and disease, with membrane-embedded proteins being particularly challenging for the cell. In order to protect the cell from consequences of defects in membrane proteins, quality control systems act to maintain protein homeostasis. The majority of these pathways act post-translationally; however, recent evidence reveals that membrane proteins are also subject to co-translational quality control during their synthesis in the endoplasmic reticulum (ER). This newly identified quality control pathway employs components of the cytosolic ribosome-associated quality control (RQC) machinery but differs from canonical RQC in that it responds to biogenesis state of the substrate rather than mRNA aberrations. This ER-associated RQC (ER-RQC) is sensitive to membrane protein misfolding and malfunctions in the ER insertion machinery. In this Review, we discuss the advantages of co-translational quality control of membrane proteins, as well as potential mechanisms of substrate recognition and degradation. Finally, we discuss some outstanding questions concerning future studies of ER-RQC of membrane proteins.
A Cuboidal Cu4S4 Cluster Supported by Bulky Iminothiolate Ligands: Synthesis, Solid-State Structure, and Solution Study
Authors: Ozawa Yoshiki , Iida Hiroki , Kiyooka Hidetoshi , Nobori Kazutaka , Tahara Keishiro , Ono Toshikazu , Abe Masaaki
Published: November 2020

A new tetracopper(I) complex containing a cuboidal Cu4S4 core, [Cu4(dap)4], where dap− is dibenzodiazepinethiolate(1–), has been synthesized and structurally characterized by single-crystal X-ray diffraction analysis. The monoanionic iminothiolate ligand dap− renders the cluster framework exceptionally stable to retain the tetranuclear structure in solution, which allows us to examine for the first time the solution properties of this class of clusters, including UV-vis and NMR spectroscopy and cyclic voltammetry.
Pyrene-Cored Hole-Transporting Materials for Efficient and Stable Perovskite Solar Cells
Authors: Shao Jiang-Yang , Zhong Yu-Wu
Published: November 2020

The use of hole-transporting materials (HTMs) is crucial in achieving high photovoltaic performance in perovskite solar cells (PSCs). Considering the high-cost, difficult synthesis, and/or the device stability issues of the commonly used HTMs such as spiro-OMeTAD, PTAA, and PEDOT:PSS, the development of low-cost and highly-efficient HTMs for stable PSCs has received intense attention. In this Account, we summarize the recent advances of the design and synthesis of new organic HTMs with a pyrene backbone for efficient and stable PSCs, including small molecular HTMs, electropolymerized films as dopant-free HTMs, and a pyrene-cored sulfur-rich molecule as an interfacial layer of PSCs. Among the devices with these materials, the best power conversion efficiency of over 20% has been achieved.
Good and Bad of Cu/Zn-Superoxide Dismutase Controlled by Metal Ions and Disulfide Bonds
Authors: Furukawa Yoshiaki
Published: November 2020

Cu/Zn-superoxide dismutase (SOD1) is a metalloenzyme that catalyzes the disproportionation of superoxide. This review summarizes intracellular processes for metal binding and disulfide formation in SOD1, both of which are essential to stabilization of the protein structure as well as its enzymatic function. Also, failure of those processes as a possible cause of a neurodegenerative disease through protein misfolding will be described.