bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+CD38+ central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART
Authors: Song Cheng-Bo , Zhang Le-Le , Wu Xian , Fu Ya-Jing , Jiang Yong-Jun , Shang Hong , Zhang Zi-Ning 
Published: February 2020

AbstractBackgroundDespite the effective antiretroviral treatment (ART) of HIV-infected individuals, HIV persists in a small pool. Central memory CD4+T cells (Tcm) make a major contribution to HIV persistence. We found that unlike HLA-DR, CD38 is highly expressed on the Tcm of HIV-infected subjects receiving ART for > 5 years. It has been reported that the half-life of total and episomal HIV DNA in the CD4+CD38+T cell subset, exhibits lower decay rates at 12 weeks of ART. Whether CD38 contributes to HIV latency in HIV-infected individuals receiving long-term ART is yet to be addressed.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of HIV-infected subjects receiving suppressive ART. The immunophenotyping, proliferation and apoptosis of CD4+T cell subpopulations were detected by flow cytometry, and the level of CD38 mRNA and total HIV DNA were measured using real-time PCR and digital droplet PCR, respectively. A negative binomial regression model was used to determine the correlation between CD4+CD38+Tcm and total HIV DNA in CD4+T cells.ResultsCD38 was highly expressed on CD4+Tcm cells from HIV infected individuals on long-term ART. Comparing with HLA-DR−Tcm and CD4+HLA-DR+T cells, CD4+CD38+Tcm cells displayed lower levels of activation (CD25 and CD69) and higher levels of CD127 expression. The proportion of CD38+Tcm, but not CD38−Tcm cells can predict the total HIV DNA in the CD4+T cells and the CD38+Tcm subset harbored higher total HIV DNA copy numbers than the CD38−Tcm subset. After transfected with CD38 si-RNA in CD4+T cells, the proliferation of CD4+T cells was inhibited.ConclusionThe current date indicates that CD4+CD38+Tcm cells contribute to HIV persistence in HIV-infected individuals on long-term ART. Our study provides a potential target to resolve HIV persistence.
Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection
Authors: Li Si-Yao , Zhang Zi-Ning , Jiang Yong‑Jun , Fu Ya‑Jing , Shang Hong 
Published: February 2020

Abstract
Background
Disease progression in the absence of therapy varies significantly in mono-HIV and HCV infected individuals. Virus-specific CD8+ T cells play an important role in restricting lentiviral replication and determining the rate of disease progression during HIV and HCV mono- and co-infection. Thus, understanding the similarities in the characteristics of CD8+ T cells in mono-HIV and HCV infection at the transcriptomic level contributes to the development of antiviral therapy. In this study, a meta-analysis of CD8+ T cell gene expression profiles derived from mono-HIV and HCV infected individuals at different stages of disease progression, was conducted to understand the common changes experienced by CD8+ T cells.

Methods
Five microarray datasets, reporting CD8+ T cell mRNA expression of the mono-HIV and HCV infected patients, were retrieved from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified via integrative meta-analysis of expression data (INMEX) program. Network analysis methods were used to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs. MirDIP and miRDB online prediction tools were used to predict potential microRNAs (miRNAs) targeting hub genes.

Results
First, we identified 625 and 154 DEGs in the CD8+ T cells originating from mono-HIV and HCV chronic progressor patients, respectively, compared to healthy individuals. Among them, interferon-stimulated genes (ISGs) including ISG15, IFIT3, ILI44L, CXCL8, FPR1 and TLR2, were upregulated after mono-HIV and HCV infection. Pathway enrichment analysis of DEGs showed that the “cytokine–cytokine receptor interaction” and “NF-kappa B” signaling pathways were upregulated after mono-HIV and HCV infection. In addition, we identified 92 and 50 DEGs in the CD8+ T cells of HIV non-progressor and HCV resolver patients, respectively, compared with corresponding chronic progressors. We observed attenuated mitosis and reduced ISG expression in HIV non-progressors and HCV resolvers compared with the corresponding chronic progressors. Finally, we identified miRNA-143-3p, predicted to target both IFIT3 in HIV and STAT5A in HCV infection.

Conclusions
We identified DEGs and transcriptional patterns in mono-HIV and HCV infected individuals at different stages of disease progression and identified miRNA-143-3p with potential to intervene disease progression, which provides a new strategy for developing targeted therapies.
ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma
Authors: Lu Jun , Chen Zhan , Zhao Hu , Dong Huiyue , Zhu Ling , Zhang Yi , Wang Jie , Zhu Hehuan , Cui Qiang , Qi Chuang , Wang Shuiliang , Chen Shushang , Shao Jichun 
Published: February 2020

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming. ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells.

Methods
The gene expression levels of ABAT and ALDH6A1 in ccRCC were analyzed from gene expression microarray datasets and RNA sequencing data. Clinical information was analyzed from The Cancer Genome Atlas (TCGA) data. The distributions of ABAT and ALDH6A1 in ccRCC clinical tissues were screened by reverse transcription-quantitative polymerase chain reaction (RT-QPCR) and immunohistochemical assays. The effect of overexpression of ABAT or ALDH6A1 was measured by detecting the cell viability, migration ability, and the ratio of lactate and nicotinamide adenine dinucleotide phosphate (NADPH). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried out to investigate the transcript regulation of HNF4A in ABAT and ALDH6A1.

Results
Remarkable downregulated ABAT and ALDH6A1 expression levels were observed in ccRCC patients and low expression of ABAT and ALDH6A1 was correlated with poor survival. Overexpression of ABAT or ALDH6A1 significantly attenuated cell proliferation and migration, and impaired lactate production. In ABAT increased ccRCC cells, the ratio of NADPH/NADP+ was reduced. Finally, we demonstrated that ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A.

Conclusions
These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.
Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)
Authors: Lim Eun-Jin , Ahn Yo-Chan , Jang Eun-Su , Lee Si-Woo , Lee Su-Hwa , Son Chang-Gue 
Published: February 2020

AbstractBackgroundChronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment.MethodsWe systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies.ResultsA total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48–0.97]. The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48–0.97]) vs. men (0.86% [95% CI 0.48–0.97]), community-based samples (0.76% [95% CI 0.53–1.10]) vs. primary care sites (0.63% [95% CI 0.37–1.10]), adults ≥ 18 years (0.65% [95% CI 0.43–0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22–1.35]), CDC-1994 (0.89% [95% CI 0.60–1.33]) vs. Holmes (0.17% [95% CI 0.06–0.49]), and interviews (1.14% [95% CI 0.76–1.72]) vs. physician diagnosis (0.09% [95% CI 0.05–0.13]), respectively.ConclusionsThis study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.
Biomechanical and physiological differences between synchronous and asynchronous low intensity handcycling during practice-based learning in able-bodied men
Authors: Kraaijenbrink Cassandra , Vegter Riemer J. K. , Hensen Alexander H. R. , Wagner Heiko , van der Woude Lucas H. V. 
Published: February 2020

AbstractBackgroundOriginally, the cranks of a handcycle were mounted with a 180° phase shift (asynchronous). However, as handcycling became more popular, the crank mode switched to a parallel mounting (synchronous) over the years. Differences between both modes have been investigated, however, not into great detail for propulsion technique or practice effects. Our aim is to compare both crank modes from a biomechanical and physiological perspective, hence considering force and power production as a cause of physiological outcome measures. This is done within a practice protocol, as it is expected that motor learning takes place in the early stages of handcycling in novices.MethodsTwelve able-bodied male novices volunteered to take part. The experiment consisted of a pre-test, three practice sessions and a post-test, which was subsequently repeated for both crank modes in a counterbalanced manner. In each session the participants handcycled for 3 × 4 minutes on a leveled motorized treadmill at 1.94 m/s. Inbetween sessions were 2 days of rest. 3D forces, handlebar and crank angle were measured on the left hand side. Kinematic markers were placed on the handcycle to monitor the movement on the treadmill. Lastly, breath-by-breath spirometry combined with heart-rate were continuously measured. The effects of crank mode and practice-based learning were analyzed using a two way repeated measures ANOVA, with synchronous vs asynchronous and pre-test vs post-test as within-subject factors.ResultsIn the pre-test, asynchronous handcycling was less efficient than synchronous handcycling in terms of physiological strain, force production and timing. At the post-test, the metabolic costs were comparable for both modes. The force production was, also after practice, more efficient in the synchronous mode. External power production, crank rotation velocity and the distance travelled back and forwards on the treadmill suggest that asynchronous handcycling is more constant throughout the cycle.ConclusionsAs the metabolic costs were reduced in the asynchronous mode, we would advise to include a practice period, when comparing both modes in scientific experiments. For handcycle users, we would currently advise a synchronous set-up for daily use, as the force production is more effective in the synchronous mode, even after practice.
Chemokine CXCL13 in serum, CSF and blood–CSF barrier function: evidence of compartment restriction
Authors: Pilz Georg , Sakic Irma , Wipfler Peter , Kraus Jörg , Haschke-Becher Elisabeth , Hitzl Wolfgang , Trinka Eugen , Harrer Andrea 
Published: February 2020

AbstractBackground and purposeElevation of the chemokine CXCL13 in CSF frequently occurs during active and acute CNS inflammatory processes and presumably is associated with B cell-related immune activation. Elevation levels, however, vary a lot and “leaking” of CXCL13 from blood across dysfunctional brain barriers is a possible source. The aim was to clarify the relation between CXCL13 concentrations in CSF, CXCL13 concentrations in serum and blood–CSF barrier (BCSFB) function for a correct interpretation of the intrathecal origin of CXCL13.MethodsWe retrospectively analyzed CXCL13 of banked CSF/serum samples (n = 69) selected from patient records and categorized the CSF CXCL13 elevations as CXCL13 negative (< 30 pg/ml), low (30–100 pg/ml), medium (101–250 pg/ml), or high (> 250 pg/ml). CXCL13 concentrations in CSF and serum and the corresponding CSF/serum CXCL13 quotients (Qcxcl13) were compared to CSF/serum albumin quotients (QAlb) as a measure for BCSFB function. The CXCL13 negative category included two subgroups with normal and dysfunctional BCSFB.ResultsSerum CXCL13 concentrations were similar across categories with median levels around 100 pg/ml but differed between individuals (29 to > 505 pg/ml). Despite clear evidence in serum, CXCL13 was detectable only at trace amounts (medians 3.5 and 7.5 pg/ml) in CSF of the two CXCL13 negative subgroups irrespective of a normal or pathological QAlb. Moreover, we found no association between CSF and serum CXCL13 levels or between QAlb and CSF CXCL13 levels in any of the CSF CXCL13-delineated categories. CXCL13 apparently does not “leak” from blood into CSF. This implies an intrathecal origin also for low CSF CXCL13 levels and a caveat for analyzing the Qcxcl13, because higher serum than CSF concentrations arithmetically depress the Qcxcl13 resulting in misleadingly low CSF/serum quotients.ConclusionWe demonstrated that CXCL13 does not cross from blood into CSF, not even during severe BCSFB dysfunction. CSF CXCL13 elevations therefore most likely always are CNS-derived, which highlights their relevance as indicator of inflammatory CNS processes. We recommend data should not be corrected for BCSFB permeability (QAlb) and not to calculate CSF/serum quotients for CXCL13 as these may introduce error.
Aberrant expression of miR-214 is associated with obesity-induced insulin resistance as a biomarker and therapeutic
Authors: Cheng Fangxiao , Yuan Geheng , He Jiao , Shao Yimin , Zhang Junqing , Guo Xiaohui 
Published: February 2020

Abstract
Background
Insulin resistance (IR) in obesity is associated with the occurrence of metabolic and cardiovascular diseases. Dipepidyl peptidase 4 (DPP4) plays a pivotal role during the development of IR, and was found to be a target gene of microRNA-214 (miR-214) in our study. This study sought to assess the expression and clinical value of miR-214 in obese patients with IR, and investigate its therapeutic potential in obese rats and adipocytes with IR.

Methods
Serum expression of miR-214 in obese patients with or without IR was estimated by quantitative real-time-PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic value of miR-214 in the patients. Obesity-induced IR animal and cell models were constructed, and the therapeutic ability of miR-214 was explored.

Results
Serum expression of miR-214 was decreased in obese patients compared with the healthy controls, and the lowest expression was observed in the cases with IR. Downregulation of miR-214 was significantly correlated with the serum DPP4 levels and HOMA-IR of the patients upon IR conditions, and was demonstrated to perform diagnostic accuracy for distinguishing obese patients with IR from those without IR. In obesity-associated IR animal and cell models, the downregulation of miR-214 was also been detected. According to the measurement of glucose and insulin tolerance and glucose uptake abilities, we found that the overexpression of miR-214 could be used to alleviate IR in the IR models, especially when collaboratively used with DPP4 inhibitor vildagliptin.

Conclusion
All data revealed that miR-214, as a regulator of DPP4, is decreased in obese patients with IR and may serve as a diagnostic biomarker. The upregulation of miR-214 could improve IR in obese rats and adipocytes, indicating that miR-214 has the therapeutic potential for obesity and IR.
A small-scale fractionation pipeline for rapid analysis of seed mucilage characteristics
Authors: Cowley James M. , Herliana Lina , Neumann Kylie A. , Ciani Silvano , Cerne Virna , Burton Rachel A. 
Published: February 2020

Abstract
Background
Myxospermy is a process by which the external surfaces of seeds of many plant species produce mucilage—a polysaccharide-rich gel with numerous fundamental research and industrial applications. Due to its functional properties the mucilage can be difficult to remove from the seed and established methods for mucilage extraction are often incomplete, time-consuming and unnecessarily wasteful of precious seed stocks.

Results
Here we tested the efficacy of several established protocols for seed mucilage extraction and then downsized and adapted the most effective elements into a rapid, small-scale extraction and analysis pipeline. Within 4 h, three chemically- and functionally-distinct mucilage fractions were obtained from myxospermous seeds. These fractions were used to study natural variation and demonstrate structure–function links, to screen for known mucilage quality markers in a field trial, and to identify research and industry-relevant lines from a large mutant population.

Conclusion
The use of this pipeline allows rapid analysis of mucilage characteristics from diverse myxospermous germplasm which can contribute to fundamental research into mucilage production and properties, quality testing for industrial manufacturing, and progressing breeding efforts in myxospermous crops.
Three-dimensional meniscus allograft sizing—a study of 280 healthy menisci
Authors: Beeler Silvan , Jud Lukas , von Atzigen Marco , Sutter Reto , Fürnstahl Philipp , Fucentese Sandro F. , Vlachopoulos Lazaros 
Published: February 2020

Abstract
Background
Inaccurate meniscus allograft size is still an important problem of the currently used sizing methods. The purpose of this study was to evaluate a new three-dimensional (3D) meniscus-sizing method to increase the accuracy of the selected allografts.

Methods
3D triangular surface models were generated from 280 menisci based on 50 bilateral and 40 unilateral knee joint magnetic resonance imaging (MRI) scans. These models served as an imaginary meniscus allograft tissue bank. Meniscus sizing and allograft selection was simulated for all 50 bilateral knee joints by (1) the closest mean surface distance (MeSD) (3D-MRI sizing with contralateral meniscus), (2) the smallest meniscal width/length difference in MRI (2D-MRI sizing with contralateral meniscus), and (3) conventional radiography as proposed by Pollard (2D-radiograph (RX) sizing with ipsilateral tibia plateau). 3D shape and meniscal width, length, and height were compared between the original meniscus and the selected meniscus using the three sizing methods.

Results
Allograft selection by MeSD (3D MRI) was superior for all measurement parameters. In particular, the 3D shape was significantly improved (p < 0.001), while the mean differences in meniscal width, length, and height were only slightly better than the allograft selected by the other methods. Outliers were reduced by up to 55% (vs. 2D MRI) and 83% (vs. 2D RX) for the medial meniscus and 39% (vs. 2D MRI) and 56% (vs. 2D RX) for the lateral meniscus.

Conclusion
3D-MRI sizing by MeSD using the contralateral meniscus as a reconstruction template can significantly improve meniscus allograft selection. Sizing using conventional radiography should probably not be recommended.

Trial registration
Kantonale Ethikkommission Zürich had given the approval for the study (BASEC-No. 2018-00856).
Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD
Authors: Andrade Nadja S. , Ramic Melina , Esanov Rustam , Liu Wenjun , Rybin Mathew J. , Gaidosh Gabriel , Abdallah Abbas , Del’Olio Samuel , Huff Tyler C. , Chee Nancy T. , Anatha Sadhana , Gendron Tania F. , Wahlestedt Claes , Zhang Yanbin , Benatar Michael , Mueller Christian , Zeier Zane 
Published: February 2020

Abstract
Background
The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. The C9ORF72 expansion encodes five dipeptide repeat proteins (DPRs) that are produced through a non-canonical translation mechanism. Among the DPRs, proline-arginine (PR), glycine-arginine (GR), and glycine-alanine (GA) are the most neurotoxic and increase the frequency of DNA double strand breaks (DSBs). While the accumulation of these genotoxic lesions is increasingly recognized as a feature of disease, the mechanism(s) of DPR-mediated DNA damage are ill-defined and the effect of DPRs on the efficiency of each DNA DSB repair pathways has not been previously evaluated.

Methods and results
Using DNA DSB repair assays, we evaluated the efficiency of specific repair pathways, and found that PR, GR and GA decrease the efficiency of non-homologous end joining (NHEJ), single strand annealing (SSA), and microhomology-mediated end joining (MMEJ), but not homologous recombination (HR). We found that PR inhibits DNA DSB repair, in part, by binding to the nucleolar protein nucleophosmin (NPM1). Depletion of NPM1 inhibited NHEJ and SSA, suggesting that NPM1 loss-of-function in PR expressing cells leads to impediments of both non-homologous and homology-directed DNA DSB repair pathways. By deleting NPM1 sub-cellular localization signals, we found that PR binds NPM1 regardless of the cellular compartment to which NPM1 was directed. Deletion of the NPM1 acidic loop motif, known to engage other arginine-rich proteins, abrogated PR and NPM1 binding. Using confocal and super-resolution immunofluorescence microscopy, we found that levels of RAD52, a component of the SSA repair machinery, were significantly increased iPSC neurons relative to isogenic controls in which the C9ORF72 expansion had been deleted using CRISPR/Cas9 genome editing. Western analysis of post-mortem brain tissues confirmed that RAD52 immunoreactivity is significantly increased in C9ALS/FTD samples as compared to controls.

Conclusions
Collectively, we characterized the inhibitory effects of DPRs on key DNA DSB repair pathways, identified NPM1 as a facilitator of DNA repair that is inhibited by PR, and revealed deficits in homology-directed DNA DSB repair pathways as a novel feature of C9ORF72-related disease.