bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charting the diversity of uncultured viruses of Archaea and Bacteria
Authors: Coutinho F. H. , Edwards R. A. , Rodríguez-Valera F. 
Published: December 2019

Abstract
Background
Viruses of Archaea and Bacteria are among the most abundant and diverse biological entities on Earth. Unraveling their biodiversity has been challenging due to methodological limitations. Recent advances in culture-independent techniques, such as metagenomics, shed light on the unknown viral diversity, revealing thousands of new viral nucleotide sequences at an unprecedented scale. However, these novel sequences have not been properly classified and the evolutionary associations between them were not resolved.

Results
Here, we performed phylogenomic analysis of nearly 200,000 viral nucleotide sequences to establish GL-UVAB: Genomic Lineages of Uncultured Viruses of Archaea and Bacteria. The pan-genome content of the identified lineages shed light on some of their infection strategies, potential to modulate host physiology, and mechanisms to escape host resistance systems. Furthermore, using GL-UVAB as a reference database for annotating metagenomes revealed elusive habitat distribution patterns of viral lineages and environmental drivers of community composition.

Conclusions
These findings provide insights about the genomic diversity and ecology of viruses of prokaryotes. The source code used in these analyses is freely available at https://sourceforge.net/projects/gluvab/.
Proteoglycan serglycin promotes non-small cell lung cancer cell migration through the interaction of its glycosaminoglycans with CD44
Authors: Guo Jing-You , Chiu Chu-Hsuan , Wang Mei-Jung , Li Fu-An , Chen Jeou-Yuan 
Published: January 2020

AbstractBackgroundSerglycin (SRGN), previously recognized as an intracellular proteoglycan involved in the storage processes of secretory granules, has recently been shown to be upregulated in several solid tumors. We have previously shown that SRGN in non-small cell lung cancer (NSCLC) promotes malignant phenotypes in a CD44-dependent manner and increased expression of SRGN predicts poor prognosis of primary lung adenocarcinomas. However, the underlying mechanism remains to be defined.MethodsOverexpression, knockdown and knockout approaches were performed to assess the role of SRGN in cell motility using wound healing and Boyden chamber migration assays. SRGN devoid of glycosaminoglycan (GAG) modification was produced by site-directed mutagenesis or chondroitinase treatment. Liquid chromatography/tandem mass spectrometry was applied for quantitative analysis of the disaccharide compositions and sulfation extent of SRGN GAGs. Western blot and co-immunoprecipitation analyses were performed to determine the expression and interaction of proteins of interest. Actin cytoskeleton organization was monitored by immunofluorescence staining.ResultsSRGN expressed by NSCLC cells is readily secreted to the extracellular matrix in a heavily glycosylated form attached with mainly chondroitin sulfate (CS)-GAG chains, and to a lesser extent with heparin sulfate (HS). The CS-GAG moiety serves as the structural motif for SRGN binding to tumor cell surface CD44 and promotes cell migration. SRGN devoid of CS-GAG modification fails to interact with CD44 and has lost the ability to promote cell migration. SRGN/CD44 interaction promotes focal adhesion turnover via Src-mediated paxillin phosphorylation and disassembly of paxillin/FAK adhesion complex, facilitating cell migration. In support, depletion of Src activity or removal of CS-GAGs efficiently blocks SRGN-mediated Src activation and cell migration. SRGN also promotes cell migration via inducing cytoskeleton reorganization mediated through RAC1 and CDC42 activation accompanied with increased lamellipodia and filopodia formation.ConclusionsProteoglycan SRGN promotes NSCLC cell migration via the binding of its GAG motif to CD44. SRGN/CD44 interaction induces Rho-family GTPase-mediated cytoskeleton reorganization and facilitates Src-mediated focal adhesion turnover, leading to increased cell migration. These findings suggest that targeting specific glycans in tumor microenvironment that serve as ligands for oncogenic pathways may be a potential strategy for cancer therapy.
Adherence to malaria rapid diagnostic test result among healthcare workers in Sokoto metropolis, Nigeria
Authors: Na’uzo Aliyu Mamman , Tukur Dahiru , Sufiyan Mu’awiyyah Babale , Stephen Adebowale Ayo , Ajayi IkeOluwapo , Bamgboye Eniola , Gobir Abdulrazaq Abdullahi , Umeokonkwo Chukwuma David , Abdullahi Zainab , Ajumobi Olufemi 
Published: January 2020

AbstractBackgroundPresumptive diagnosis and prescription of anti-malarial medicines to malaria rapid diagnostic test (RDT)-negative patients is a common practice among health care workers (HCWs) in Nigeria. There is paucity of data on HCWs adherence to RDT result in Sokoto metropolis, Nigeria. The study was conducted to determine HCWs adherence to malaria test result and the influencing factors.MethodsA cross-sectional study was conducted among 262 HCWs selected by multistage sampling technique from primary and secondary health facilities in Sokoto metropolis. Data on demographic characteristics, adherence to RDT result and its influencing factors were collected from the HCWs. Adherence was categorized into good if adherence score is ≥ 4 and poor if otherwise. Chi-squared test was used to test association between adherence to test results and patients’ fever presentation, expectation to be given anti-malarials, prior HCWs’ case management training, among others. Independent predictors of adherence to RDT results were ascertained.ResultsRespondents’ mean age was 33.5 ± 7.9 years, 190 (72.5%) worked in Primary Health Care facilities, 112 (42.8%) were Community Health Workers, 178 (67.9%) had National Diploma Certificate. The median years of practice was 5.0 (IQR: 3–10) years, while 118 (45.0%) had at most 4 years of practice. Overall, 211 (80.5%) had good adherence to RDT results. About 108 (89.3%) of HCWs who had training on malaria case management and 35 (89.7%) certificate holders had good adherence to RDT results. Predictors of adherence to test results were presence of fever in the patient [adjusted odds ratio (aOR): 2.53, 95% confidence interval (CI) 1.18–5.43], patients’ expectation to be given anti-malarial medicines by the HCW (aOR: 3.06, 95% CI 1.42–6.58) and having been trained on malaria case management (aOR: 2.63; 95% CI 1.26–5.44).ConclusionHigh level of adherence to RDT results among HCWs in Sokoto metropolis could be attributed to prior malaria case management training and HCWs’ confidence in the national treatment guidelines. Continual training and supportive supervision of HCWs on malaria case management might optimize the current level of adherence to RDT results in Sokoto metropolis, Nigeria. Similarly, patients/caregivers’ health education could aid better understanding of the need for anti-malarials thus reducing unnecessary demand.
The interactome and proteomic responses of ALKBH7 in cell lines by in-depth proteomics analysis
Authors: Meng Shu , Zhan Shaohua , Dou Wanchen , Ge Wei 
Published: December 2019

Abstract
Background
ALKBH7 is a mitochondrial protein, involved in programmed necrosis, fatty acid metabolism, cell cycle regulation, and prostate cancer disease. However, the exact roles of ALKBH7 and the underlying molecular mechanisms remain mysterious. Thus, investigations of the interactome and proteomic responses of ALKBH7 in cell lines using proteomics strategies are urgently required.

Methods
In the present study, we investigated the interactome of ALKBH7 in mitochondria through immunoprecipitation-mass spectrometry/mass spectrometry (IP-MS/MS). Additionally, we established the ALKBH7 knockdown and overexpression cell lines and further identified the differentially expressed proteins (DEPs) in these cell lines by TMT-based MS/MS. Two DEPs (UQCRH and HMGN1) were validated by western blotting analysis.

Results
Through bioinformatic analysis the proteomics data, we found that ALKBH7 was involved in protein homeostasis and cellular immunity, as well as cell proliferation, lipid metabolism, and programmed necrosis by regulating the expression of PTMA, PTMS, UQCRH, HMGN1, and HMGN2. Knockdown of ALKBH7 resulted in upregulation of UQCRH and HMGN1 expression, and the opposite pattern of expression was detected in ALKBH7 overexpression cell lines; these results were consistent with our proteomics data.

Conclusion
Our findings indicate that the expression of UQCRH and HMGN1 is regulated by ALKBH7, which provides potential directions for future studies of ALKBH7. Furthermore, our results also provide comprehensive insights into the molecular mechanisms and pathways associated with ALKBH7.
Assessing quality of life in older adults: psychometric properties of the OPQoL-brief questionnaire in a nursing home population
Authors: Haugan Gørill , Drageset Jorunn , André Beate , Kukulu Kamile , Mugisha James , Utvær Britt Karin S. 
Published: January 2020

Abstract
Background
Well-adapted and validated quality-of-life measurement models for the nursing home population are scarce. Therefore, the aim of this study was to test the psychometrical properties of the OPQoL-brief questionnaire among cognitively intact nursing home residents. The research question addressed evidence related to the dimensionality, reliability and construct validity, all of which considered interrelated measurement properties.

Methods
Cross-sectional data were collected during 2017–2018, in 27 nursing homes representing four different Norwegian municipalities, located in Western and Mid-Norway. The total sample comprised 188 of 204 (92% response rate) long-term nursing home residents who met the inclusion criteria: (1) municipality authority’s decision of long-term nursing home care; (2) residential time 3 months or longer; (3) informed consent competency recognized by responsible doctor and nurse; and (4) capable of being interviewed.

Results
Principal component analysis and confirmative factor analyses indicated a unidimensional solution. Five of the original 13 items showed low reliability and validity; excluding these items revealed a good model fit for the one-dimensional 8-items measurement model, showing good internal consistency and validity for these 8 items.

Conclusion
Five out of the 13 original items were not high-quality indicators of quality-of-life showing low reliability and validity in this nursing home population. Significant factor loadings, goodness-of-fit indices and significant correlations in the expected directions with the selected constructs (anxiety, depression, self-transcendence, meaning-in-life, nurse-patient interaction, and joy-of-life) supported the psychometric properties of the OPQoL-brief questionnaire. Exploring the essence of quality-of-life when residing in a nursing home is highly warranted, followed by development and validation of new tools assessing quality-of-life in this population. Such knowledge and well-adapted scales for the nursing home population are beneficial and important for the further development of care quality in nursing homes, and consequently for quality-of-life and wellbeing in this population.
Rabbit VX2 lung tumor models can form early nodal metastases
Authors: Gregor Alexander , Fujino Kosuke , Bernards Nicholas , Kinoshita Tomonari , Motooka Yamato , Inage Terunaga , Ishiwata Tsukasa , Chen Zhenchian , Ujiie Hideki , Lee Chang Young , Yasufuku Kazuhiro 
Published: December 2019

Abstract
Background
The rabbit squamous cell cancer line, VX2, has been used to generate various tumor models in rabbits. It is notable for its ability to generate nodal metastases. However, the timing and extent of nodal metastases vary by primary inoculation site and methodology. The development of metastases specifically in lung cancer models has not been well-described. We sought to characterize the generation of nodal metastases in rabbit transbronchial VX2 lung tumor models.

Methods
Rabbit VX2 lung tumor models were created in the right lung via transbronchial injection and serially imaged by computed tomography. Rabbits (n = 15) were sacrificed from between 5 and 24 days post-inoculation for collection of the ipsilateral and contralateral paratracheal lymph nodes. These underwent histopathological evaluation for metastases using hematoxylin and eosin as well as cytokeratin AE1/AE3 immunohistochemical staining.

Results
Nodal metastases were detectable as early as 1 week after inoculation but were more prevalent with longer inoculation; all rabbits at > 2 weeks post-inoculation had nodal metastases. Contralateral metastases were in general seen later than ipsilateral metastases. Lymph node volume did not predict the likelihood of nodal metastases (p = 0.4 and p = 0.07 for ipsilateral and contralateral nodal metastases, respectively), but primary tumor volume was significantly associated with the likelihood of nodal metastases (p = 0.001 and p = 0.005 for ipsilateral and contralateral nodal metastases, respectively). Ipsilateral metastases were detectable at a tumor diameter of 1 cm; contralateral metastases were more variable but in general required a tumor diameter of 2 cm.

Conclusions
Rabbit transbronchial VX2 lung tumor models generate nodal metastases relatively early after inoculation. These results suggest such models may be valuable tools in the investigation of novel therapeutic modalities relevant for the treatment of both early-stage and locally advanced lung cancer.
The importance of ultrasound in identifying and differentiating patients with early inflammatory arthritis: a narrative review
Authors: Kaeley Gurjit S. , Bakewell Catherine , Deodhar Atul 
Published: January 2020

AbstractEarly differentiation between different types of inflammatory arthritis and subsequent initiation of modern treatments can improve patient outcomes by reducing disease activity and preventing joint damage. Routine clinical evaluation, laboratory testing, and radiographs are typically sufficient for differentiating between inflammatory and predominantly degenerative arthritis (e.g., osteoarthritis). However, in some patients with inflammatory arthritis, these techniques fail to accurately identify the type of early-stage disease. Further evaluation by ultrasound imaging can delineate the inflammatory arthritis phenotype present. Ultrasound is a noninvasive, cost-effective method that enables the evaluation of several joints at the same time, including functional assessments. Further, ultrasound can visualize pathophysiological changes such as synovitis, tenosynovitis, enthesitis, bone erosions, and crystal deposits at a subclinical level, which makes it an effective technique to identify and differentiate most common types of inflammatory arthritis. Limitations associated with ultrasound imaging should be considered for its use in the differentiation and diagnosis of inflammatory arthritides.
Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: the OFELY study
Authors: Rousseau Jean-Charles , Millet Marjorie , Croset Martine , Sornay-Rendu Elisabeth , Borel Olivier , Chapurlat Roland 
Published: January 2020

Abstract
Objectives
In the context of the scarcity of biomarkers for knee osteoarthritis (OA), we examined the associations of prevalent and incident OA with the expression levels of serum miRNAs in subjects with and without OA.

Methods
With a next-generation sequencing approach, we compared the miRome expression of 10 women with knee OA and 10 age-matched healthy subjects. By real-time qPCR, we analyzed the expression levels of 19 miRNAs at baseline selecting 43 women with prevalent knee OA (Kellgren Lawrence score of 2/3), 23 women with incident knee OA over a 4-year follow-up and 67 healthy subjects without prevalent or incident OA matched for age and body mass index.

Results
Serum miR-146a-5p was significantly increased in the group of prevalent knee OA compared with controls (relative quantification (RQ); median [Interquartile range] 1.12 [0.73; 1.46] vs 0.85 [0.62; 1.03], p = 0.015). The likelihood of prevalent knee OA was significantly increased (odds ratio [95% confidence interval (CI)] 1.83 [1.21–2.77], p = 0.004) for each quartile increase in serum miR-146a-5p. The women with miR-146a-5p levels above the median (0.851) had a higher risk of prevalent knee OA compared to those below the median [95% CI] 4.62 [1.85–11.5], p = 0.001. Moreover, we found a significant association between the baseline level of serum miR-186-5p and the risk of incident knee OA (Q4 vs Q1–3; odds ratio [95% CI] 6.13 [1.14–32.9], p = 0.034).

Conclusion
We showed for the first time that miR-146a-5p and miR-186-5p are significantly associated with prevalent and incident knee OA, respectively.
A re-evaluation of LINE-1 ORF2 expression in LNCaP prostate cancer cells
Authors: Briggs Erica M. , Spadafora Corrado , Logan Susan K. 
Published: December 2019

Abstract
Background
We previously examined expression of Long Interspersed Element-1 (LINE-1) in a variety of prostate cancer cells including hormone-dependent LNCaP cells. These studies demonstrated expression and sub-cellular localization of LINE-1 proteins, ORF1p, with antibody 4H1, and ORF2p, with antibody chA1-L1.

Results
Here we conduct immunoprecipitation/mass spectrometry analysis using chA1-L1 antibody against ORF2p in LNCaP cells. Our results indicate that antigens detected by the antibody include the transcriptional regulator BCLAF1. We show that chA1-L1 recognizes BCLAF1 using siRNA knockdown and overexpression of a tagged BCLAF1. We also show that chA1-L1 antibody recognizes ORF2p in HEK293 cells overexpressing LINE-1. Further, analysis of ORF2p (chA1-L1) and BCLAF1 foci using immunofluorescence in LNCaP cells showed significant colocalization.

Conclusions
Overall, our findings indicate that chA1-L1 antibody recognizes both BCLAF1 and ORF2p but the majority of antigen recognized in LNCaP cells is BCLAF1.
One-month-old girl presenting with pseudohypoaldosteronism leading to the diagnosis of CDK13-related disorder: a case report and review of the literature
Authors: Yakubov Renata , Ayman Asaly , Kremer Adi Klein , van den Akker Machiel 
Published: December 2019

Abstract
Background
It is not uncommon that an infant with a disease of unknown etiology is presented to a physician. Facial dysmorphic features lead to a different diagnosis. It is a challenge to link the presentation to the newfound diagnosis.

Case presentation
A 37-day-old Yemenite Jewish girl was presented to our institution with a clinical picture of pseudohypoaldosteronism due to abnormal facial features and a psychomotor developmental delay. Further investigation led to the diagnosis of CDK13-related disorder. According to the literature, CDK13 has a key role in the cell cycle, but no interference with the aldosterone signaling pathway or electrolyte balance was described. No mutations in the previously described gene NR3C2 (cytogenetic location 4q31.23), encoding the mineralocorticoid receptor, were found. Although the clinical presentation corresponded to pseudohypoaldosteronism type 1, we could not genetically confirm this.

Conclusions
Probably pseudohypoaldosteronism was a coincidental finding in this girl with a CDK13 mutation, but because only limited information is known about CDK13-related disorders, further investigation could be more informative to clarify this presentation.
Health insurance coverage, type of payment for health insurance, and reasons for not being insured under the National Health Insurance Scheme in Ghana
Authors: Ayanore Martin Amogre , Pavlova Milena , Kugbey Nuworza , Fusheini Adam , Tetteh John , Ayanore Augustine Adoliba , Akazili James , Adongo Philip Baba , Groot Wim 
Published: December 2019

Abstract
Background
Ghana’s National Health Insurance Scheme has improved access to care, although equity and sustainability issues remain. This study examined health insurance coverage, type of payment for health insurance and reasons for being uninsured under the National Health Insurance Scheme in Ghana.

Methods
The 2014 Ghana Demographic Health Survey datasets with information for 9396 women and 3855 men were analyzed. The study employed cross-sectional national representative data. The frequency distribution of socio-demographics and health insurance coverage differentials among men and women is first presented. Further statistical analysis applies a two-stage probit Hackman selection model to determine socio-demographic factors associated with type of payment for insurance and reasons for not insured among men and women under the National Health insurance Scheme in Ghana. The selection equation in the Hackman selection model also shows the association between insurance status and socio-demographic factors.

Results
About 66.0% of women and 52.6% of men were covered by health insurance. Wealth status determined insurance status, with poorest, poorer and middle-income groups being less likely to pay themselves for insurance. Women never in union and widowed women were less likely to be covered relative to married women although this group was more likely to pay NHIS premiums themselves. Wealth status (poorest, poorer and middle-income) was associated with non-affordability as a reason for being not insured. Geographic disparities were also found. Rural men and nulliparous women were also more likely to mention no need of insurance as a reason of being uninsured.

Conclusion
Tailored policies to reduce delays in membership enrolment, improve positive perceptions and awareness of National Health Insurance Scheme in reducing catastrophic spending and addressing financial barriers for enrolment among some groups can be positive precursors to improve trust and enrolments and address broad equity concerns regarding the National Health Insurance Scheme.
The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis
Authors: Hu Xingdi , Wildman Kingsley P. , Basu Subham , Lin Peggy L. , Rowntree Clare , Saha Vaskar 
Published: December 2019

Abstract
Background
L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting.

Results
In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age.

Conclusions
Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease.

Trial registration
UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22.