bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of antimicrobial prescribing for dental and oral infections in England and Scotland with Norway and Sweden and their relative contribution to national consumption 2010–2016
Authors: Smith Andrew , Al-Mahdi Rania , Malcolm William , Palmer Nikolaus , Dahlen Gunnar , Al-Haroni Mohammed 
Published: June 2020

Abstract
Background
Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010–2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption.

Methods
This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs100,000).

Results
A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden.

Conclusion
Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.
Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies
Authors: Bu Fan-Long , Feng Xue , Yang Xiao-Ying , Ren Jun , Cao Hui-Juan 
Published: June 2020

Abstract
Background
For a long time, the relationship between caffeine consumption and infertility in the general population is unclear, this study is aimed to systematically review the evidence from any type of controlled clinical studies to explore whether caffeine intake is a risk factor for human infertility.

Methods
Seven databases were searched from inception to May 2019. We included women/men without a history of infertility but were willing to have children in prospective studies and women/men who were diagnosed with infertility in retrospective studies. The observed exposure factor should be caffeine or caffeine containing beverage. Diagnosis of infertility or not for participants was the key outcome. The Newcastle-Ottawa scale (NOS) or Cochrane risk of bias tool were used to assess the methodological quality of included studies. Meta-analysis was conducted if there were acceptable clinical and statistical heterogeneity among studies. The GRADE method was used to assess the certainty of the evidence.

Results
Four studies (one cohort study and three case-control studies) involving 12,912 participants were included. According NOS, the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78–1.16), medium (OR 1.14, 95%CI 0.69–1.86) and high doses (OR 1.86, 95%CI 0.28–12.22) of caffeine intake may not increase the risk of infertility. The quality of the current evidence bodies were all low.

Conclusion
Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution.
Public preferences regarding data linkage for research: a discrete choice experiment comparing Scotland and Sweden
Authors: Tully Mary P. , Bernsten Cecilia , Aitken Mhairi , Vass Caroline 
Published: June 2020

Abstract
Background
There are increasing examples of linking data on healthcare resource use and patient outcomes from different sectors of health and social care systems. Linked data are generally anonymised, meaning in most jurisdictions there are no legal restrictions to their use in research conducted by public or private organisations. Secondary use of anonymised linked data is contentious in some jurisdictions but other jurisdictions are known for their use of linked data. The publics’ perceptions of the acceptability of using linked data is likely to depend on a number of factors. This study aimed to quantify the preferences of the public to understand the factors that affected views about types of linked data and its use in two jurisdictions.

Method
An online discrete choice experiment (DCE) previously conducted in Scotland was adapted and replicated in Sweden. The DCE was designed, comprising five attributes, to elicit the preferences from a representative sample of the public in both jurisdictions. The five attributes (number of levels) were: type of researcher using linked data (four); type of data being linked (four); purpose of the research (three); use of profit from using linked data (four); who oversees the research (four). Each DCE contained 6 choice-sets asking respondents to select their preferred option from two scenarios or state neither were acceptable. Background questions included socio-demographics. DCE data were analysed using conditional and heteroskedastic conditional logit models to create forecasts of acceptability.

Results
The study sample comprised members of the public living in Scotland (n = 1004) and Sweden (n = 974). All five attributes were important in driving respondents’ choices. Swedish and Scottish preferences were mostly homogenous with the exception of ‘who oversees the research using linked data’, which had relatively less impact on the choices observed from Scotland. For a defined ‘typical’ linked data scenario, the probability (on average) of acceptance was 85.7% in Sweden and 82.4% in Scotland.

Conclusion
This study suggests that the public living in Scotland and Sweden are open to using anonymised linked data in certain scenarios for research purposes but some caution is advisable if the anonymised linked data joins health to non-health data.
A national survey of private-sector outpatient care of sick infants and young children in Nepal
Authors: Ban Bharat , Hodgins Stephen , Thapa Pranita , Thapa Surakschha , Joshi Deepak , Dhungana Adhish , KC Anjana , Guenther Tanya , Adhikari Shilu , Scudder Elaine , Ram Pavani K. 
Published: June 2020

Abstract
Background
Previous research has documented that across South Asia, as well as in some countries in Sub-Saharan Africa, the private sector is the primary source of outpatient care for sick infants and children and, in many settings, informal providers play a bigger role than credentialed health professionals (particularly for the poorer segments of the population). This is the case in Nepal. This study sought to characterize medicine shop-based service providers in rural areas and small urban centers in Nepal, their role in the care and treatment of sick infants and children (with a particular focus on infants aged < 2 months), and the quality of the care provided. A secondary objective was to characterize availability and quality of such care provided by physicians in these settings.

Methods
A nationally representative sample of medicine shops was drawn, in rural settings and small urban centers in Nepal, from 25 of the 75 districts in Nepal, using multi-stage cluster methodology, with a final sample of 501 shops and 82 physician-run clinics. Face-to-face interviews were conducted.

Results
Most medicine shops outside urban areas were not registered with the Department of Drug Administration (DDA). Most functioned as de facto clinics, with credentialed paramedical workers (having 2–3 years of training) diagnosing patients and making treatment decisions. Such a role falls outside their formally sanctioned scope of practice. Quality of care problems were identified among medicine shop-based providers and physicians, including over-use of antibiotics for treating diarrhea, inaccurate weighing technique to determine antibiotic dose, and inappropriate use of injectable steroids for treating potentially severe infections in young infants.

Conclusions
Medicine shop-based practitioners in Nepal represent a particular type of informal provider; although most have recognized paramedical credentials, they offer services falling outside their formal scope of practice. Nevertheless, given the large proportion of the population served by these practitioners, engagement to strengthen quality of care by these providers and referral to the formal health sector is warranted.
Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii
Authors: Kloehn Joachim , Oppenheim Rebecca D. , Siddiqui Ghizal , De Bock Pieter-Jan , Kumar Dogga Sunil , Coute Yohann , Hakimi Mohamed-Ali , Creek Darren J. , Soldati-Favre Dominique 
Published: June 2020

AbstractBackgroundAcetyl-CoA is a key molecule in all organisms, implicated in several metabolic pathways as well as in transcriptional regulation and post-translational modification. The human pathogenToxoplasma gondiipossesses at least four enzymes which generate acetyl-CoA in the nucleo-cytosol (acetyl-CoA synthetase (ACS); ATP citrate lyase (ACL)), mitochondrion (branched-chain α-keto acid dehydrogenase-complex (BCKDH)) and apicoplast (pyruvate dehydrogenase complex (PDH)). Given the diverse functions of acetyl-CoA, we know very little about the role of sub-cellular acetyl-CoA pools in parasite physiology.ResultsTo assess the importance and functions of sub-cellular acetyl-CoA-pools, we measured the acetylome, transcriptome, proteome and metabolome of parasites lacking ACL/ACS or BCKDH. We demonstrate that ACL/ACS constitute a synthetic lethal pair. Loss of both enzymes causes a halt in fatty acid elongation, hypo-acetylation of nucleo-cytosolic and secretory proteins and broad changes in gene expression. In contrast, loss of BCKDH results in an altered TCA cycle, hypo-acetylation of mitochondrial proteins and few specific changes in gene expression. We provide evidence that changes in the acetylome, transcriptome and proteome of cells lacking BCKDH enable the metabolic adaptations and thus the survival of these parasites.ConclusionsUsing multi-omics and molecular tools, we obtain a global and integrative picture of the role of distinct acetyl-CoA pools inT. gondiiphysiology. Cytosolic acetyl-CoA is essential and is required for the synthesis of parasite-specific fatty acids. In contrast, loss of mitochondrial acetyl-CoA can be compensated for through metabolic adaptations implemented at the transcriptional, translational and post-translational level.
FBXO2 modulates STAT3 signaling to regulate proliferation and tumorigenicity of osteosarcoma cells
Authors: Zhao Xunming , Guo Weichun , Zou Lixue , Hu Biao 
Published: June 2020

Abstract
Background
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, and hyperproliferation of cells is a major problem of OS. FBXO2 belongs to the family of F-box proteins, and is a substrate recognition component of the Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex with specificity for high-mannose glycoproteins. The aim of the present study was to investigate the critical role of FBXO2 in OS cells.

Methods
The protein and mRNA expression levels of FBXO2 in clinic OS patients were measured by quantitative real time-polymerase chain reaction (qRT-PCR), Western blot and Immunohistochemical (IHC) staining assays, respectively. The FBXO2 overexpression model was constructed by retro-virus transfection in OS cells. FBXO2 knockout (KO) cells were generated by Clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein 9 (Cas9) assay. Cell counting and colony formation assays were used to analyze the effect of FBXO2 on the biological function of OS cells. FBXO2 KO cells were injected into nude mice to observe tumor growth in vivo. The interaction between FBXO2 and IL-6 was detected by immunoprecipitation. Luciferase assay was used to determine the transcriptional activity of STAT3.

Results
Here, we show that FBXO2 is significantly up-regulated in clinical OS samples compared to adjacent normal tissues. Ectopic expression of FBXO2 leads to increased OS cell proliferation and colony-forming ability, while FBXO2 knockout by CRISPR-Cas9-based gene editing has the opposite effect. In addition, the glycoprotein recognition activity of FBXO2 is required for its biological function in OS. In vivo experiments showed that FBXO2 knockout greatly impaired the tumorigenicity of OS cells in nude mice. At the molecular level, we found that knocking out FBXO2 can significantly inhibit STAT3 phosphorylation and downstream target gene expression through IL-6R stabilization.

Conclusion
Together, these results indicate that FBXO2 promotes OS development by activating the STAT3 signaling pathway, suggesting that FBXO2 may be a new target for OS treatment.
Assessment of attitudes toward functional foods based on theory of planned behavior: validation of a questionnaire
Authors: Salmani Fatemeh , Norozi Ensiyeh , Moodi Mitra , Zeinali Tayebeh 
Published: June 2020

Abstract
Background
The objectives of this study are to construct a cultural adopted questionnaire for evaluation of consumer’s attitudes toward functional foods among Iranian’s population according to Theory of Planned Behavior (TPB) and to investigate the attitudes toward vitamin enriched foods (VEF).

Methods
Participants were students of Birjand University of Medical Sciences (BUMS). Exploratory factor analysis (EFA), Confirmatory Factor Analysis (CFA) and reliability assessment were performed. The construct validity of questionnaire determined by EFA and confirmed by CFA.

Results
The overall Cronbach’s alpha of questionnaire was 0.78. The three domains of TPB model were significantly associated with the total score of attitude toward functional foods questionnaire (AFFQ). Attitudes and subjective norms could successfully predict the consumption of VEF (p < 0.023 and p < 0.001, respectively), but perceived control construct could not perform the prediction (p < 0.219).

Conclusion
AFFQ is a valid and reliable instrument to measure the attitudes of consumers toward consumption of functional foods in Iran.
Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults
Authors: Pertiwi Kamalita , Küpers Leanne K. , Geleijnse Johanna M. , Zock Peter L. , Wanders Anne J. , Kruger Herculina S. , van Zyl Tertia , Kruger Iolanthé M. , Smuts Cornelius M. 
Published: June 2020

Abstract
Background
The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated.

Methods
Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression.

Results
Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (β per 1 SD: − 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (β (95% confidence interval): − 0.25 (− 0.31, − 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality.

Conclusion
Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function.

Trial registration
PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).
Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China
Authors: Hou Jingyuan , Deng Qiaoting , Guo Xuemin , Deng Xunwei , Zhong Wei , Zhong Zhixiong 
Published: June 2020

Abstract
Background
Apolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China.

Methods
The APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip.

Results
The prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10–2.05, P = 0.010).

Conclusions
The present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.
Combining texture features of whole slide images improves prognostic prediction of recurrence-free survival for cutaneous melanoma patients
Authors: Peng Yanbin , Chu Yunfeng , Chen Zhong , Zhou Wen , Wan Shengxiang , Xiao Yingfeng , Zhang Youlong , Li Jialu 
Published: June 2020

Abstract
Background
Accurate prediction of recurrence-free survival (RFS) is important for the prognosis of cutaneous melanoma patients. The image-based pathological examination remains as the gold standard for diagnosis. It is of clinical interest to account for computer-aided processing of pathology image when performing prognostic analysis.

Methods
We enrolled in this study a total of 152 patients from TCGA-SKCM (The Cancer Genome Atlas Skin Cutaneous Melanoma project) with complete information in recurrence-related survival time, baseline variables (clinicopathologic variables, mutation status of BRAF and NRAS genes), gene expression data, and whole slide image (WSI) features. We preprocessed WSI to segment global or nucleus areas, and extracted 3 types of texture features from each region. We performed cross validation and used multiple evaluation metrics including C-index and time-dependent AUC to determine the best model of predicting recurrence events. We further performed differential gene expression analysis between the higher and lower-risk groups within AJCC pathologic tumor stage III patients to explore the underlying molecular mechanisms driving risk stratification.

Results
The model combining baseline variables and WSI features had the best performance among models with any other types of data integration. The prognostic risk score generated by this model could provide a higher-resolution risk stratification within pathologically defined subgroups. We found the selected image features captured important immune-related variations, such as the aberration of expression in T cell activation and proliferation gene sets, and therefore contributed to the improved prediction.

Conclusions
Our study provided a prognostic model based on the combination of baseline variables and computer-processed WSI features. This model provided more accurate prediction than models based on other types of data combination in recurrence-free survival analysis.

Trial registration
This study was based on public open data from TCGA and hence the study objects were retrospectively registered.
The TNF/TNFR2 signaling pathway is a key regulatory factor in endothelial progenitor cell immunosuppressive effect
Authors: Naserian Sina , Abdelgawad Mohamed Essameldin , Afshar Bakshloo Mazdak , Ha Guillaume , Arouche Nassim , Cohen José L. , Salomon Benoît L. , Uzan Georges 
Published: June 2020

Abstract
Background
Endothelial progenitor cells (EPCs) are non-differentiated endothelial cells (ECs) present in blood circulation that are involved in neo-vascularization and correction of damaged endothelial sites. Since EPCs from patients with vascular disorders are impaired and inefficient, allogenic sources from adult or cord blood are considered as good alternatives. However, due to the reaction of immune system against allogenic cells which usually lead to their elimination, we focused on the exact role of EPCs on immune cells, particularly, T cells which are the most important cells applied in immune rejection. TNFα is one of the main activators of EPCs that recognizes two distinct receptors. TNFR1 is expressed ubiquitously and its interaction with TNFα leads to differentiation and apoptosis, whereas, TNFR2 is expressed predominantly on ECs, immune cells and neural cells and is involved in cell survival and proliferation. Interestingly, it has been shown that different immunosuppressive cells express TNFR2 and this is directly related to their immunosuppressive efficiency. However, little is known about immunological profile and function of TNFR2 in EPCs.

Methods
Using different in-vitro combinations, we performed co-cultures of ECs and T cells to investigate the immunological effect of EPCs on T cells. We interrupted in the TNFα/TNFR2 axis either by blocking the receptor using TNFR2 antagonist or blocking the ligand using T cells derived from TNFα KO mice.

Results
We demonstrated that EPCs are able to suppress T cell proliferation and modulate them towards less pro-inflammatory and active phenotypes. Moreover, we showed that TNFα/TNFR2 immune-checkpoint pathway is critical in EPC immunomodulatory effect.

Conclusions
Our results reveal for the first time a mechanism that EPCs use to suppress immune cells, therefore, enabling them to form new immunosuppressive vessels. Furthermore, we have shown the importance of TNFα/TNFR2 axis in EPCs as an immune checkpoint pathway. We believe that targeting TNFR2 is especially crucial in cancer immune therapy since it controls two crucial aspects of tumor microenvironment: 1) Immunosuppression and 2) Angiogenesis.