bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome mining of novel rubiginones from Streptomyces sp. CB02414 and characterization of the post-PKS modification steps in rubiginone biosynthesis
Authors: Zhang Jingyan , Sun Ying , Wang Yeji , Chen Xin , Xue Lu , Zhang Jingjing , Zhu Xiangcheng , Duan Yanwen , Yan Xiaohui 
Published: October 2021

Abstract
Background
Rubiginones belong to the angucycline family of aromatic polyketides, and they have been shown to potentiate the vincristine (VCR)-induced cytotoxicity against VCR-resistant cancer cell lines. However, the biosynthetic gene clusters (BGCs) and biosynthetic pathways for rubiginones have not been reported yet.

Results
In this study, based on bioinformatics analysis of the genome of Streptomyces sp. CB02414, we predicted the functions of the two type II polyketide synthases (PKSs) BGCs. The rub gene cluster was predicted to encode metabolites of the angucycline family. Scale-up fermentation of the CB02414 wild-type strain led to the discovery of eight rubiginones, including five new ones (rubiginones J, K, L, M, and N). Rubiginone J was proposed to be the final product of the rub gene cluster, which features extensive oxidation on the A-ring of the angucycline skeleton. Based on the production profiles of the CB02414 wild-type and the mutant strains, we proposed a biosynthetic pathway for the rubiginones in CB02414.

Conclusions
A genome mining strategy enabled the efficient discovery of new rubiginones from Streptomyces sp. CB02414. Based on the isolated biosynthetic intermediates, a plausible biosynthetic pathway for the rubiginones was proposed. Our research lays the foundation for further studies on the mechanism of the cytochrome P450-catalyzed oxidation of angucyclines and for the generation of novel angucyclines using combinatorial biosynthesis strategies.
Multivalent poultry vaccine development using Protein Glycan Coupling Technology
Authors: Mauri Marta , Sannasiddappa Thippeswamy H. , Vohra Prerna , Corona-Torres Ricardo , Smith Alexander A. , Chintoan-Uta Cosmin , Bremner Abi , Terra Vanessa S. , Abouelhadid Sherif , Stevens Mark P. , Grant Andrew J. , Cuccui Jon , Wren Brendan W. ,   the Glycoengineering of Veterinary Vaccines Consortium
Published: October 2021

Abstract
Background
Poultry is the world's most popular animal-based food and global production has tripled in the past 20 years alone. Low-cost vaccines that can be combined to protect poultry against multiple infections are a current global imperative. Glycoconjugate vaccines, which consist of an immunogenic protein covalently coupled to glycan antigens of the targeted pathogen, have a proven track record in human vaccinology, but have yet to be used for livestock due to prohibitively high manufacturing costs. To overcome this, we use Protein Glycan Coupling Technology (PGCT), which enables the production of glycoconjugates in bacterial cells at considerably reduced costs, to generate a candidate glycan-based live vaccine intended to simultaneously protect against Campylobacter jejuni, avian pathogenic Escherichia coli (APEC) and Clostridium perfringens. Campylobacter is the most common cause of food poisoning, whereas colibacillosis and necrotic enteritis are widespread and devastating infectious diseases in poultry.

Results
We demonstrate the functional transfer of C. jejuni protein glycosylation (pgl) locus into the genome of APEC χ7122 serotype O78:H9. The integration caused mild attenuation of the χ7122 strain following oral inoculation of chickens without impairing its ability to colonise the respiratory tract. We exploit the χ7122 pgl integrant as bacterial vectors delivering a glycoprotein decorated with the C. jejuni heptasaccharide glycan antigen. To this end we engineered χ7122 pgl to express glycosylated NetB toxoid from C. perfringens and tested its ability to reduce caecal colonisation of chickens by C. jejuni and protect against intra-air sac challenge with the homologous APEC strain.

Conclusions
We generated a candidate glycan-based multivalent live vaccine with the potential to induce protection against key avian and zoonotic pathogens (C. jejuni, APEC, C. perfringens). The live vaccine failed to significantly reduce Campylobacter colonisation under the conditions tested but was protective against homologous APEC challenge. Nevertheless, we present a strategy towards the production of low-cost “live-attenuated multivalent vaccine factories” with the ability to express glycoconjugates in poultry.
Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease
Authors: Mei Xi , Qiu Conglong , Zhou Qi , Chen Zhongming , Chen Yang , Xu Zemin , Zou Chenjun 
Published: October 2021

Abstract
Background
Retinal biomarkers of Alzheimer’s disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD.

Objective
Our study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs).

Methods
Non-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters.

Results
Seventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 μm), FRTs of the four quadrants (290.35 ± 13.05 μm of inferior quadrant, 294.68 ± 9.37 μm of superior quadrant, 302.97 ± 6.52 μm of nasal quadrant, 286.02 ± 13.74 μm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892.

Conclusion
Our study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology.
Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx
Structural geometries and mechanical properties of vertebral implant with honeycomb sandwich structure for vertebral compression fractures: a finite element analysis
Authors: Guo Yuan , Liu Jing , Zhang Xushu , Xing Zejun , Chen Weiyi , Huang Di 
Published: October 2021

Abstract
Background
Because of osteoporosis, traffic accidents, falling from high places, and other reasons, the vertebral body can be compressed and even collapse. Vertebral implants can be used for clinical treatment. Because of the advantages of honeycomb sandwich structures, such as low cost, less material, light weight, high strength, and good cushioning performance. In this paper, the honeycomb sandwich structure was used as the basic structure of vertebral implants.

Methods
The orthogonal experiment method is applied to analyse the size effect of honeycomb sandwich structures by the finite element method. Based on the minimum requirements of three indexes of peak stress, axial deformation, and anterior–posterior deformation, the optimal structure size was determined. Furthermore, through local optimization of the overall structure of the implant, a better honeycomb sandwich structure vertebral implant was designed.

Results
The optimal structure size combination was determined as a panel thickness of 1 mm, wall thickness if 0.49 mm, cell side length of 1 mm, and height of 6 mm. Through local optimization, the peak stress was further reduced, the overall stress distribution was uniform, and the deformation was reduced. The optimized peak stress decreased to 1.041 MPa, the axial deformation was 0.1110%, and the anterior–posterior deformation was 0.0145%. A vertebral implant with good mechanical performance was designed.

Conclusions
This paper is the first to investigate vertebral implants with honeycomb sandwich structures. The design and analysis of the vertebral implant with a honeycomb sandwich structure were processed by the finite element method. This research can provide a feasible way to analyse and design clinical implants based on biomechanical principles.
Overexpression of lncRNAs with endogenous lengths and functions using a lncRNA delivery system based on transposon
Authors: Zhang Yin , Huang Yong-Xin , Jin Xin , Chen Jie , Peng Li , Wang Dan-Lan , Li Yun , Yao Xin-Yi , Liao Jian-You , He Jie-Hua , Hu KaiShun , Lu Daning , Guo Yabin , Yin Dong 
Published: October 2021

Abstract
Background
Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes, this indicates that lncRNAs can serve as potential targets for gene therapy. Stable expression is a fundamental technology in the study of lncRNAs. The lentivirus is one of the most widely used delivery systems for stable expression. However, it was initially designed for mRNAs, and the applicability of lentiviral vectors for lncRNAs is largely unknown.

Results
We found that the lentiviral vector produces lncRNAs with improper termination, appending an extra fragment of ~ 2 kb to the 3ʹ-end. Consequently, the secondary structures were changed, the RNA–protein interactions were blocked, and the functions were impaired in certain lncRNAs, which indicated that lentiviral vectors are not ideal delivery systems of lncRNAs. Here, we developed a novel lncRNA delivery method called the Expression of LncRNAs with Endogenous Characteristics using the Transposon System (ELECTS). By inserting a termination signal after the lncRNA sequence, ELECTS produces transcripts without 3ʹ-flanking sequences and retains the native features and function of lncRNAs, which cannot be achieved by lentiviral vectors. Moreover, ELECTS presents no potential risk of infection for the operators and it takes much less time. ELECTS provides a reliable, convenient, safe, and efficient delivery method for stable expression of lncRNAs.

Conclusions
Our study demonstrated that improper transcriptional termination from lentiviral vectors have fundamental effects on molecular action and cellular function of lncRNAs. The ELECTS system developed in this study will provide a convenient and reliable method for the lncRNA study.

Graphic Abstract
Dizziness and health-related quality of life among older adults in an urban population: a cross-sectional study
Authors: Lindell Ellen , Kollén Lena , Johansson Mia , Karlsson Therese , Rydén Lina , Fässberg Madeleine Mellqvist , Erhag Hanna Falk , Skoog Ingmar , Finizia Caterina 
Published: October 2021

AbstractBackgroundDizziness is a common complaint among older adults and may affect quality of life in a negative way. The aim of this study was to assess health-related quality of life (HRQL), sense of coherence (SOC), self-rated health (SRH) and comorbidity in relation to dizziness, among older persons from an urban population.MethodsThe study is part of the Gothenburg H70 Birth Cohort Studies (H70). A cross-sectional population-based sample including 662 79-years-olds (404 women, 258 men, 62% response rate) were surveyed with questions regarding dizziness, imbalance, comorbidities and general health. HRQL was assessed using the 36-item Short Form-36 Health Survey (SF-36) and SOC with the 13-items questionnaire Sense of Coherence (SOC-13).ResultsHalf of the participants reported problems with dizziness (54%). Dizziness was negatively associated with HRQL, including after adjusting for comorbidities, especially in the physical domains of SF-36. Having dizziness was also associated with poorer SRH, tiredness and comorbidity among both men and women. SOC (mean total score), however, did not differ between dizzy and non-dizzy participants.ConclusionsDizziness was negatively associated with HRQL, also after adjusting for comorbidities. Identification and treatment of dizziness, when possible, are important because reduction of dizziness symptoms may potentially help to enhance overall well-being in this age group.
Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis
Authors: Chen Xiehui , Huang Weichao , Sun Aimei , Wang Lili , Mo Fanrui , Guo Wenqin 
Published: October 2021

Abstract
Background
This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin.

Methods
PubMed, the Cochrane Library database, clinicaltrial.gov, and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH).

Results
Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03–1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15–20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36–7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68–4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25–4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different.

Conclusions
The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.
Mortality trends in chronic liver disease and cirrhosis from 1981 to 2015 in Taiwan
Authors: Su Shih-Yung , Lee Long-Teng , Lee Wen-Chung 
Published: October 2021

Abstract
Background
Globally, the morbidity and mortality rates for chronic liver disease and cirrhosis are increasing. The National Viral Hepatitis Therapy Program in Taiwan was implemented in 2003, but evidence regarding the program’s effect on the trends of mortality for chronic liver disease and cirrhosis is limited.

Methods
We analyzed mortality rates for chronic liver disease and cirrhosis in Taiwan for the period from 1981 to 2015. An autoregressive age–period–cohort model was used to estimate age, period, and cohort effects.

Results
Age-adjusted mortality rates for chronic liver disease and cirrhosis all displayed a flat but variable trend from 1981 to 2004 and a decreasing trend thereafter for both sexes. The age–period–cohort model revealed differential age gradients between the two sexes; mortality rates in the oldest age group (90–94 years) were 12 and 66 times higher than those in the youngest age group (30–34 years) for men and women, respectively. The period effects indicated that mortality rates declined after 2004 in both sexes. Mortality rates decreased in men but increased in women in the 1891–1940 birth cohorts and increased in both sexes in the birth cohorts from 1950 onward.

Conclusions
The National Viral Hepatitis Therapy Program in Taiwan may have contributed to the decrease in mortality rates for chronic liver disease and cirrhosis in adulthood.
Knowledge about juvenile idiopathic arthritis-associated uveitis: more frequent reminders are associated with higher patient and family uveitis knowledge
Authors: Cooper Ashley M. , Flanagan Elaine R. , Ronis Tova , Goldberg Baruch , Sherman Ashley K. , Smith Chelsey , Holland Gary N. ,   for the CARRA Uveitis Workgroup
Published: October 2021

AbstractBackgroundChronic anterior uveitis is a sight-threatening complication of juvenile idiopathic arthritis (JIA) and a primary contributor to long-term morbidity in people with JIA. Levels of knowledge about uveitis among JIA patients and their parents are unknown. A survey of JIA patients and parents was conducted to assess knowledge about uveitis complications and recommended screening.MethodsA survey was developed consisting of six demographic questions, six arthritis/uveitis history questions, and nine uveitis knowledge questions. The survey was administered to JIA patients age 14 and older and parents of patients with JIA at three pediatric rheumatology practices and online through the Patients, Advocates, and Rheumatology Teams Network for Research and Service (PARTNERS) network. ANOVA, chi-square and Fisher’s exact tests were used to look for relationships between survey questions and demographic variables.ResultsThirty-three patients and 111 parents completed the survey. Overall, 17.4% reported a history of uveitis, and 89.6% had heard of uveitis. The mean composite knowledge score was 6.46 ± 2.6 out of 9. Patients and parents with a history of uveitis had higher composite knowledge scores than their counterparts without a uveitis history (p = 0.01 andp < 0.01, respectively). Parents whose rheumatologist reminded them about eye exams at every visit had higher knowledge of the risk of blindness (p = 0.04), the risk for uveitis when arthritis is controlled (p = 0.02), the need for ongoing eye exams when off of medications (p = 0.01), and had a higher overall score (p = 0.02) than those who were reminded at some visits or not at all.ConclusionsJIA patients and parents report variable levels of knowledge regarding uveitis complications and recommended screening. Frequent discussion between the rheumatology provider and family about uveitis screening is associated with higher uveitis knowledge. Incorporating detailed and frequent education about uveitis into rheumatology clinic appointments may improve early uveitis detection and visual outcomes.
Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation
Authors: Sogorb-Esteve Aitana , Swift Imogen J. , Woollacott Ione O. C. , Warren Jason D. , Zetterberg Henrik , Rohrer Jonathan D. 
Published: October 2021

Abstract
Background
The primary progressive aphasias (PPA) represent a group of usually sporadic neurodegenerative disorders with three main variants: the nonfluent or agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). They are usually associated with a specific underlying pathology: nfvPPA with a primary tauopathy, svPPA with a TDP-43 proteinopathy, and lvPPA with underlying Alzheimer’s disease (AD). Little is known about their cause or pathophysiology, but prior studies in both AD and svPPA have suggested a role for neuroinflammation. In this study, we set out to investigate the role of chemokines across the PPA spectrum, with a primary focus on central changes in cerebrospinal fluid (CSF)

Methods
Thirty-six participants with sporadic PPA (11 svPPA, 13 nfvPPA, and 12 lvPPA) as well as 19 healthy controls were recruited to the study and donated CSF and plasma samples. All patients with lvPPA had a tau/Aβ42 biomarker profile consistent with AD, whilst this was normal in the other PPA groups and controls. We assessed twenty chemokines in CSF and plasma using Proximity Extension Assay technology: CCL2 (MCP-1), CCL3 (MIP-1a), CCL4 (MIP-1β), CCL7 (MCP-3), CCL8 (MCP-2), CCL11 (eotaxin), CCL13 (MCP-4), CCL19, CCL20, CCL23, CCL25, CCL28, CX3CL1 (fractalkine), CXCL1, CXCL5, CXCL6, CXCL8 (IL-8), CXCL9, CXCL10, and CXCL11.

Results
In CSF, CCL19 and CXCL6 were decreased in both svPPA and nfvPPA compared with controls whilst CXCL5 was decreased in the nfvPPA group with a borderline significant decrease in the svPPA group. In contrast, CCL2, CCL3 and CX3CL1 were increased in lvPPA compared with controls and nfvPPA (and greater than svPPA for CX3CL1). CXCL1 was also increased in lvPPA compared with nfvPPA but not the other groups. CX3CL1 was significantly correlated with CSF total tau concentrations in the controls and each of the PPA groups. Fewer significant differences were seen between groups in plasma, although in general, results were in the opposite direction to CSF, i.e. decreased in lvPPA compared with controls (CCL3 and CCL19), and increased in svPPA (CCL8) and nfvPPA (CCL13).

Conclusion
Differential alteration of chemokines across the PPA variants is seen in both CSF and plasma. Importantly, these results suggest a role for neuroinflammation in these poorly understood sporadic disorders, and therefore also a potential future therapeutic target.
Next generation sequencing based in-house HIV genotyping method: validation report
Authors: Ayitewala Alisen , Ssewanyana Isaac , Kiyaga Charles 
Published: October 2021

Abstract
Background
HIV genotyping has had a significant impact on the care and treatment of HIV/AIDS. At a clinical level, the test guides physicians on the choice of treatment regimens. At the surveillance level, it informs policy on consolidated treatment guidelines and microbial resistance control strategies. Until recently, the conventional test has utilized the Sanger sequencing (SS) method. Unlike Next Generation Sequencing (NGS), SS is limited by low data throughput and the inability of detecting low abundant drug-resistant variants. NGS can improve sensitivity and quantitatively identify low-abundance variants; in addition, it has the potential to improve efficiency as well as lowering costs when samples are batched. Despite the NGS benefits, its utilization in clinical drug resistance profiling is faced with mixed reactions. These are largely based on a lack of a consensus regarding the quality control strategy. Nonetheless, transitional views suggest validating the method against the gold-standard SS. Therefore, we present a validation report of an NGS-based in-house HIV genotyping method against the SS method in Uganda.

Results
Since there were no established proficiency test panels for NGS-based HIV genotyping, 15 clinical plasma samples for routine care were utilized. The use of clinical samples allowed for accuracy and precision studies. The workflow involved four main steps; viral RNA extraction, targeted amplicon generation, amplicon sequencing and data analysis. Accuracy of 98% with an average percentage error of 3% was reported for the NGS based assay against the SS platform demonstrating similar performance. The coefficient of variation (CV) findings for both the inter-run and inter-personnel precision showed no variability (CV ≤ 0%) at the relative abundance of ≥ 20%. For both inter-run and inter-personnel, a variation that affected the precision was observed at 1% frequency. Overall, for all the frequencies, CV registered a small range of (0–2%).

Conclusion
The NGS-based in-house HIV genotyping method fulfilled the minimum requirements that support its utilization for drug resistance profiling in a clinical setting of a low-income country. For more inclusive quality control studies, well-characterized wet panels need to be established.