bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amphotericin B biosynthesis in Streptomyces nodosus: quantitative analysis of metabolism via LC–MS/MS based metabolomics for rational design
Authors: Zhang Bo , Zhou Yi-Teng , Jiang Sheng-Xian , Zhang Yu-Han , Huang Kai , Liu Zhi-Qiang , Zheng Yu-Guo 
Published: January 2020

Abstract
Background
Amphotericin B (AmB) is widely used against fungal infection and produced mainly by Streptomyces nodosus. Various intracellular metabolites of S. nodosus were identified during AmB fermentation, and the key compounds that related to the cell growth and biosynthesis of AmB were analyzed by principal component analysis (PCA) and partial least squares (PLS).

Results
Rational design that based on the results of metabolomics was employed to improve the AmB productivity of Streptomyces nodosus, including the overexpression of genes involved in oxygen-taking, precursor-acquiring and product-exporting. The AmB yield of modified strain S. nodosus VMR4A was 6.58 g/L, which was increased significantly in comparison with that of strain S. nodosus ZJB2016050 (5.16 g/L). This was the highest yield of AmB reported so far, and meanwhile, the amount of by-product amphotericin A (AmA) was decreased by 45%. Moreover, the fermentation time of strain S. nodosus VMR4A was shortened by 24 h compared with that of strain. The results indicated that strain S. nodosus VMR4A was an excellent candidate for the industrial production of AmB because of its high production yield, low by-product content and the fast cell growth.

Conclusions
This study would lay the foundation for improving the AmB productivity through metabolomics analysis and overexpression of key enzymes.
Multi-dimensional omics characterization in glioblastoma identifies the purity-associated pattern and prognostic gene signatures
Authors: Xiong Yi , Xiong Zujian , Cao Hang , Li Chang , Wanggou Siyi , Li Xuejun 
Published: January 2020

Abstract
Background
The presence of tumor-associated stroma and tumor-infiltrated immune cells have been largely reported across glioblastomas. Tumor purity, defined as the proportion of tumor cells in the tumor, was associated with the genomic and clinicopathologic features of the tumor and may alter the interpretation of glioblastoma biology.

Methods
We use an integrative approach to infer tumor purity based on multi-omic data and comprehensively evaluate the impact of tumor purity on glioblastoma (GBM) prognosis, genomic profiling, and the immune microenvironment in the Cancer Genome Atlas Consortium (TCGA) cohort.

Results
We found that low tumor purity was significantly associated with reduced survival time. Additionally, we established a purity-relevant 5-gene signature that was an independent prognostic biomarker and validated it in the TCGA, CGGA and GSE4412 cohort. Moreover, we correlated tumor purity with genomic characteristics and tumor microenvironment. We identified that gamma delta T cells in glioblastoma microenvironment were positively correlated with purity and served as a marker for favorable prognosis, which was validated in both TCGA and CGGA dataset.

Conclusions
We observe the potential confounding effects of tumor purity on GBM clinical and molecular information interpretation. GBM microenvironment could be purity-dependent, which provides new insights into the clinical implications of glioblastoma.
Quantitative analysis of facial asymmetry based on three-dimensional photography: a valuable indicator for asymmetrical temporomandibular joint affection in juvenile idiopathic arthritis patients?
Authors: Bernini Joëlle M. , Kellenberger Christian J. , Eichenberger Martina , Eliades Theodore , Papageorgiou Spyridon N. , Patcas Raphael 
Published: January 2020

Abstract
Background
Juvenile idiopathic arthritis (JIA) can cause osseous deformity in the temporomandibular joint (TMJ) and may impair mandibular growth. This study aimed to evaluate whether facial asymmetry determined clinically or by morphometric analysis of three-dimensional (3D) photographs in JIA patients is associated with an asymmetric affection of theTMJ.

Methods
Of 76 consecutive JIA patients with a mean age of 11.7 years (range: 6.3–17.9), facial asymmetry was evaluated clinically (chin asymmetry, gonion asymmetry), and stereophotogrammetrically with 3D photographs. The facial surfaces were demarcated, then mirrored, superimposed using semi-automated landmarks, and quantitatively assessed (chin asymmetry, Hausdorff distances). Clinical and digital measurements were related to the diagnosis of right and left TMJ involvement derived from magnetic resonance images (MRI).

Results
Twenty-seven (34%) patients had an asymmetrical osseous deformity of the TMJ. By clinical evaluation, chin asymmetry was related to asymmetrical osseous destruction (p = 0.02), but gonion asymmetry was not (p = 0.14). In regard to 3D-photograph based morphometric measurements, chin asymmetry was also related to asymmetrical osseous destruction (p = 0.01), but neither the mean (p = 0.06) nor the maximal Hausdorff distance (p = 0.67). Despite the attested significance, none of the chin asymmetry evaluation methods appeared to hold sufficient predictive value (positive predictive values ≤54%; coefficient of determination ≤7%).

Conclusions
For the assessment of facial asymmetry in JIA patients, morphometric measurements originating from 3D-photographs seem to deliver results comparable to the clinical assessment methods. The asymmetry of the face, especially around the chin, appears to be related to asymmetrical TMJ destruction, but none of the investigated measurement methods of the face were able to reliably predict the TMJ affection. Thus, facial asymmetry assessments, both qualitatively in a clinical setting and quantitatively based on 3D-photographs, have limited diagnostic value for TMJ involvement in JIA patients.
Decreased expression of Rev-Erbα in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbα have anti-inflammatory and neuroprotective effects in the pilocarpine model
Authors: Yue Jiong , He Jiaojiang , Wei Yujia , Shen Kaifeng , Wu Kefu , Yang Xiaolin , Liu Shiyong , Zhang Chunqing , Yang Hui 
Published: January 2020

AbstractBackgroundA hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model.MethodsThe expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining.ResultsThe western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1β, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE.ConclusionsTaken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects.
Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda
Authors: Ayitewala Alisen , Kyeyune Fred , Ainembabazi Pamela , Nabulime Eva , Kato Charles Drago , Nankya Immaculate 
Published: January 2020

AbstractBackgroundResistance to antiretroviral drugs is a major challenge among Human Immunodeficiency Virus (HIV) positive patients receiving antiretroviral therapy (ART). Mutations that arise as a result of this are diverse across the various drugs, drug classes, drug regimens and subtypes. In Uganda, there is a paucity of information on how these mutations differ among the different drug regimens and the predominant HIV-1 subtypes. The purpose of this study was to determine mutation profile differences between first-line drug regimens: TDF/3TC/EFV and AZT/3TC/EFV and HIV-1 subtypes: A and D in Uganda. The study also investigated the potential usage of rilpivirine, doravirine and etravirine in patients who failed treatment on efavirenz.MethodsA retrospective study was conducted on 182 archived plasma samples obtained from patients who were experiencing virological failure between 2006 and 2017 at five Joint Clinical Research Center (JCRC) sites in Uganda. Sanger sequencing of the Reverse Transcriptase (RT) gene from codons 1–300 was done. Mutation scores were generated using the Stanford University HIV Drug Resistance Database. A Chi-square test was used to determine the association between drug resistance mutations (DRMs) and drug regimens or HIV-1 subtypes.ResultsThe prevalence of DRMs was 84.6% among patients failing a first-line efavirenz (EFV)-based regimen. The most prevalent Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations were M184V/I (67.3%), K219/Q/E (22.6%) and K65R (21.1%). While K103N (50.8%) and G190A/S/E/G (29.1%) were the most prevalent Non-Nucleoside Reverse Transcriptase Inhibitor (NNTRI) mutations. As expected, discriminatory DRMs such as K65R, L74I, and Y115F were noted in Tenofovir (TDF) containing regimens while the Thymidine Analogue Mutations (TAMs) L210W and T215 mutations were in Zidovudine (AZT)-based regimens. No significant difference (p = 0.336) was found for overall DRMs between HIV-1 subtypes A and D. Among the patients who had resistance to EFV, 37 (23.6%) were susceptible to newer NNRTIs such as Rilpivirine and Etravirine.ConclusionAccumulation of DRMs between AZT/3TC/EFV and TDF/3TC/EFV is comparable but individual mutations that confer resistance to particular drugs should be considered at virological failure. Having either HIV-1 subtype A or D is not associated with the acquisition of DRMs, therefore HIV diversity should not determine the choice of treatment. Rilpivirine, etravirine and doravirine had minimal benefits for patients who failed on efavirenz.
Visual processing speed in hemianopia patients secondary to acquired brain injury: a new assessment methodology
Authors: Mena-Garcia Laura , Maldonado-Lopez Miguel J. , Fernandez Itziar , Coco-Martin Maria B. , Finat-Saez Jaime , Martinez-Jimenez Jose L. , Pastor-Jimeno Jose C. , Arenillas Juan F. 
Published: January 2020

Abstract
Background
There is a clinical need to identify diagnostic parameters that objectively quantify and monitor the effective visual ability of patients with homonymous visual field defects (HVFDs). Visual processing speed (VPS) is an objective measure of visual ability. It is the reaction time (RT) needed to correctly search and/or reach for a visual stimulus. VPS depends on six main brain processing systems: auditory-cognitive, attentional, working memory, visuocognitive, visuomotor, and executive. We designed a new assessment methodology capable of activating these six systems and measuring RTs to determine the VPS of patients with HVFDs.

Methods
New software was designed for assessing subject visual stimulus search and reach times (S-RT and R-RT respectively), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10o, 20o, and 30o). Thus, for each HVFD and control subject, 96 S- and R-RT measures related to VPS were registered. Three additional variables were measured to gather objective data on the validity of the test: eye-hand coordination mistakes (ehcM), eye-hand coordination accuracy (ehcA), and degrees of head movement (dHM, measured by a head-tracker system). HVFD patients and healthy controls (30 each) matched by age and gender were included. Each subject was assessed in a single visit. VPS measurements for HFVD patients and control subjects were compared for the complete test, for each stimulus complexity group, and for each eccentricity.

Results
VPS was significantly slower (p < 0.0001) in the HVFD group for the complete test, each stimulus complexity group, and each eccentricity. For the complete test, the VPS of the HVFD patients was 73.0% slower than controls. They also had 335.6% more ehcMs, 41.3% worse ehcA, and 189.0% more dHMs than the controls.

Conclusions
Measurement of VPS by this new assessment methodology could be an effective tool for objectively quantifying the visual ability of HVFD patients. Future research should evaluate the effectiveness of this novel method for measuring the impact that any specific neurovisual rehabilitation program has for these patients.
Isolation of Ontario aquatic bird bornavirus 1 and characterization of its replication in immortalized avian cell lines
Authors: Pham Phuc H. , Leacy Alexander , Deng Li , Nagy Éva , Susta Leonardo 
Published: January 2020

Abstract
Background
Aquatic bird bornavirus 1 (ABBV-1) has been associated with neurological diseases in wild waterfowls. In Canada, presence of ABBV-1 was demonstrated by RT-qPCR and immunohistochemistry in tissues of waterfowls with history of neurological disease and inflammation of the central and peripheral nervous tissue, although causation has not been proven by pathogenesis experiments, yet. To date, in vitro characterization of ABBV-1 is limited to isolation in primary duck embryo fibroblasts. The objectives of this study were to describe isolation of ABBV-1 in primary duck embryonic fibroblasts (DEF), and characterize replication in DEF and three immortalized avian fibroblast cell lines (duck CCL-141, quail QT-35, chicken DF-1) in order to evaluate cellular permissivity and identify suitable cell lines for routine virus propagation.

Methods
The virus was sequenced, and phylogenetic analysis performed on a segment of the N gene coding region. Virus spread in cell cultures, viral RNA and protein production, and titres were evaluated at different passages using immunofluorescence, RT-qPCR, western blotting, and tissue culture dose 50% (TCID50) assay, respectively.

Results
The isolated ABBV-1 showed 97 and 99% identity to European ABBV-1 isolate AF-168 and North American ABBV-1 isolates 062-CQ and CG-N1489, and could infect and replicate in DEF, CCL-141, QT-35 and DF-1 cultures. Viral RNA was detected in all four cultures with highest levels observed in DEF and CCL-141, moderate in QT-35, and lowest in DF-1. N protein was detected in western blots from infected DEF, CCL-141 and QT-35 at moderate to high levels, but minimally in infected DF-1. Infectious titre was highest in DEF (between approximately 105 to 106 FFU / 106 cells). Regarding immortalized cell lines, CCL-141 showed the highest titre between approximately 104 to 105 FFU / 106 cells. DF-1 produced minimal infectious titre.

Conclusions
This study confirms the presence of ABBV-1 among waterfowl in Canada and reported additional in vitro characterization of this virus in different avian cell lines. ABBV-1 replicated to highest titre in DEF, followed by CCL-141 and QT-35, and poorly in DF-1. Our results showed that CCL-141 can be used instead of DEF for routine ABBV-1 production, if a lower titre is an acceptable trade-off for the simplicity of using immortalized cell line over primary culture.
Evaluation of a new point-of-care oral anti-HCV test for screening of hepatitis C virus infection
Authors: Liu Lili , Zhang Mingyuan , Hang Lei , Kong Fei , Yan Hongqing , Zhang Yumei , Feng Xiangwei , Gao Yuanda , Wang Chang , Ma Heming , Liu Xu , Zhan Mengru , Pan Yu , Xu Hongqin , Niu Junqi 
Published: January 2020

Abstract
Background
Hepatitis C virus (HCV) infection is a public health issue for which an effective universal screening method is urgently needed. An oral anti-HCV test could provide a noninvasive and rapid screening strategy for HCV infection. This study evaluated the performance of a new point-of-care oral assay developed by Well for the detection of HCV antibody.

Methods
Individuals from three centers with and without HCV infection were enrolled. All participants were tested for oral HCV antibody using the Well assay and for serum HCV antibody using established tests (ARCHITECT i2000 anti-HCV assay and InTec serum anti-HCV assay). For participants who obtained positive results, HCV RNA was tested for verification. Some patients underwent the OraQuick HCV test at the same time, and some self-tested with the Well assay during the same period.

Results
A total of 1179 participants, including 486 patients with chronic HCV infection, 108 patients with other liver diseases, and 585 individuals who underwent physical examination, were enrolled. The Well anti-HCV test had a sensitivity of 91.88% (95% confidence interval [CI]: 88.97–94.09%) and a specificity of 98.00% (96.58–98.86%) for oral HCV antibody detection. The consistency between the Well and InTec assays was 97.02% (1138/1179). The consistency between the Well and OraQuick assays was 98.50% (197/200). Furthermore, the results of self-testing were highly consistent with those of researcher-administered tests (Kappa = 0.979). In addition, the HCV RNA results also showed that HCV RNA could only be detected on 1 of the 39 false-negative samples, and for 172 positive HCV RNA results, 171 could be detected by the Well oral anti-HCV assay.

Conclusions
The Well oral anti-HCV test offers high sensitivity and specificity and performed comparably to both the OraQuick assay and InTec assay for HCV diagnosis. Thus, the Well test represents a new tool for universal HCV screening to identify infected patients, particularly in regions with limited medical resources.
Biomechanical comparison of noncontiguous cervical disc arthroplasty and noncontiguous cervical discectomy and fusion in the treatment of noncontinuous cervical degenerative disc disease: a finite element analysis
Authors: Sun Xiangyao , Sun Siyuan , Zhang Tongtong , Kong Chao , Wang Wei , Lu Shibao 
Published: January 2020

Abstract
Background
Biomechanical characteristics of noncontinuous ACDF and noncontinuous CDA in the treatment of noncontinuous cervical degenerative disc disease were still unclear. The aim of this research is to compare the differences between these two kinds of treatment methods and to verify the effectiveness of Prodisc-C in noncontinuous CDA.

Methods
Eight FEMs of the cervical spine (C2–C7) were built based on CT images of 8 mild CDDD volunteers. In the arthroplasty group, we inserted Prodisc-C at C3/4 and C5/6. In the fusion group, CoRoent® Contour and NuVasive® Helix ACP were implanted at C3/4 and C5/6. Initial loads of 75 N were used to simulate the head weight and muscle forces. The application of 1.0 N m moment on the top on the C2 vertebra was used to create motion in all directions. Statistical analyses were performed using STATA version 14.0 (Stata Corp LP, College Station, Texas, USA). Statistical significance was set at P < 0.05.

Results
The IDPs in C2/3 (P < 0.001, P = 0.005, P < 0.001, P < 0.001), C4/5 (P < 0.001), and C6/7 (P < 0.001) of the intact group were significantly less than that in the fusion group in flexion, extension, lateral bending, and axial rotation, respectively. In addition, the IDPs in C2/3 (P < 0.001, P = 0.001, P < 0.001, P < 0.001), C4/5 (P < 0.001), and C6/7 (P < 0.001) of the arthroplasty group were significantly less than that in the fusion group in flexion, extension, lateral bending, and axial rotation, respectively. Contact forces of facet joints in C2/3 (P = 0.010) in the arthroplasty group was significantly less than that in the intact group. Contact forces of facet joints in C2/3 (P < 0.001), C4/5 (P < 0.001), and C6/7 (P < 0.001) in the arthroplasty group was significantly less than that in the fusion group. Contact forces of facet joints in C2/3 (P < 0.001), C4/5 (P < 0.001), and C6/7 (P < 0.001) in the intact group were significantly less than that in the fusion group.

Conclusions
Noncontinuous CDA could preserve IDP and facet joint forces at the adjacent and intermediate levels to maintain the kinematics of cervical spine near preoperative values. However, noncontinuous ACDF would increase degenerative risks at adjacent and intermediate levels. In addition, the application of Prodisc-C in noncontinuous CAD may have more advantages than that of Prestige LP.
The clinical outcomes of cementless unicompartmental knee replacement in patients with reduced bone mineral density
Authors: Mohammad Hasan R. , Kennedy James A. , Mellon Stephen J. , Judge Andrew , Dodd Christopher A. , Murray David W. 
Published: January 2020

AbstractBackgroundOsteoporosis and osteopenia are conditions characterised by reduced bone mineral density (BMD). There is concern that bone with reduced BMD may not provide sufficient fixation for cementless components which primarily rely on the quality of surrounding bone. The aim of our study was to report the midterm clinical outcomes of patients with reduced BMD undergoing cementless unicompartmental knee replacements (UKR). Our hypothesis was that there would be no difference in outcome between patients with normal bone and those with reduced BMD.MethodsFrom a prospective cohort of 70 patients undergoing cementless UKR surgery, patients were categorised into normal (n = 20), osteopenic (n = 38) and osteoporotic groups (n = 12) based on their central dual-energy X-ray absorptiometry (DEXA) scans according to the World Health Organization criteria. Patients were followed up by independent research physiotherapists and outcome scores; Oxford Knee Score (OKS), Tegner score, American Knee Society Score Functional (AKSS-F) and Objective (AKSS-O) were recorded preoperatively and at a mean of 4 years postoperatively. The prevalence of reoperations, revisions and mortality was also recorded at a mean of 5 years postoperatively.ResultsThere were no significant differences in the midterm postoperative OKS (P = 0.83), Tegner score (P = 0.17) and AKSS-O (P = 0.67). However, the AKSS-F was significantly higher (P = 0.04) in normal (90, IQR 37.5) compared to osteoporotic (65, IQR 35) groups. There were no significant differences (P = 0.82) between normal and osteopenic bone (80, IQR 35). The revision prevalence was 5%, 2.6% and 0% in the normal, osteopenic and osteoporotic groups respectively. The reoperation prevalence was 5%, 7.9% and 0% respectively. There were no deaths in any group related to the implant.ConclusionsWe found that patients with reduced BMD could safely undergo cementless UKR surgery and have similar clinical outcomes to those with normal BMD. However, larger studies with longer follow-up are needed to confirm our findings and ensure that cementless fixation is safe in patients with reduced BMD.