bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does prophylactic antibiotic administration for tooth extraction affect PT-INR in patients taking warfarin?
Authors: Iwata Eiji , Tachibana Akira , Kusumoto Junya , Takata Naoki , Hasegawa Takumi , Akashi Masaya 
Published: November 2020

Abstract
Background
Various antibiotics and analgesics have been reported to interact with warfarin. Reports that investigate the effects of medication taken for just a few days during tooth extraction on the prothrombin time-international normalized ratio are rare.

Methods
A total of 110 patients receiving long-term stable warfarin therapy underwent tooth extraction without interruption of warfarin treatment. INR values were measured 1 month before the tooth extraction, the day of the extraction, and 1 week after the extraction. We investigated the changes in INR values between the day of extraction and 1 week after extraction, as well as the various risk factors for increases in INR values.

Results
Before and after tooth extraction, the number of patients taking cefcapene pivoxil, amoxicillin, and azithromycin was 57, 36, and 8, respectively. Nine patients were administered ampicillin before tooth extraction and received amoxicillin after their tooth extraction. One week after tooth extraction, the INR values increased beyond the therapeutic range in 3 out of 110 patients (2.7%). The INR values before tooth extraction in these three patients were close to 3.0. The INR value increased by more than twice as much in 1 out of 110 patients (0.9%).

Conclusion
Our results suggest that prophylactic antibiotic administration has little effect on INR values when patients on stable warfarin therapy undergo tooth extraction. Surgeons have to take attention if the patients whose INR values are close to 3.0 before their extraction.
Network pharmacology exploration reveals a common mechanism in the treatment of cardio-cerebrovascular disease with Salvia miltiorrhiza Burge. and Carthamus tinctorius L
Authors: Wang Yu , Shi Yajun , Zou Junbo , Zhang Xiaofei , Liang Yulin , Tai Jia , Cui Chunli , Wang Mei , Guo Dongyan 
Published: November 2020

AbstractBackgroundThis study aimed to identify the key genes and KEGG pathways inCarthamus tinctoriusL. (Safflower) andSalvia miltiorrhizaBurge. (Salvia) for the treatment of cardio-cerebrovascular disease, and to explore their potential molecular mechanisms.MethodsCompounds and targets in Safflower and Salvia were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We obtained targets of myocardial infarction (MI) and cerebral infarction (CI) data from Therapeutic Target Database (TTD), Drugbank and DisGeNET datasets. The network of Safflower, Salvia, CI and MI was established and then executing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the functional characteristics were performed. The Chinese herbal prescription and target for CI and MI were obtained by searching in the database. Finally, the main pathways of Salvia and Safflower in Chinese patent medicines were analyzed. The MCAO model was established in rats, and compatibility of salvia with safflower was experimentally verified.ResultsWe obtained a total of 247 genes targeted by 52 compounds from Safflower and 119 genes targeted by 48 compounds from Salvia. In total, we identified 299 known therapeutic targets for the treatment of CI and 960 targets for the treatment MI. There are 23 common targets for Salvia, Safflower, MI, and CI. A total of 85 KEGG pathways were also enriched and intersected with the pathway of proprietary Chinese medicine to yield 25 main pathways. Safflower and Salvia have the best therapeutic effect in MCAO.ConclusionWe identified gene lists for Safflower and Salvia in CI and MI. Bioinformatics and interaction analyses may provide new insight into the treatment of cardio-cerebrovascular diseases with Safflower and Salvia.
Sharing genomic data from clinical testing with researchers: public survey of expectations of clinical genomic data management in Queensland, Australia
Authors: Vidgen Miranda E. , Kaladharan Sid , Malacova Eva , Hurst Cameron , Waddell Nicola 
Published: November 2020

Abstract
Background
There has been considerable investment and strategic planning to introduce genomic testing into Australia’s public health system. As more patients’ genomic data is being held by the public health system, there will be increased requests from researchers to access this data. It is important that public policy reflects public expectations for how genomic data that is generated from clinical tests is used. To inform public policy and discussions around genomic data sharing, we sought public opinions on using genomic data contained in medical records for research purposes in the Australian state of Queensland.

Methods
A total of 1494 participants completed an online questionnaire between February and May 2019. Participants were adults living in Australia. The questionnaire explored participant preferences for sharing genomic data or biological samples with researchers, and concerns about genomic data sharing.

Results
Most participants wanted to be given the choice to have their genomic data from medical records used in research. Their expectations on whether and how often they needed to be approached for permission on using their genomic data, depended on whether the data was identifiable or anonymous. Their willingness to sharing data for research purposes depended on the type of information being shared, what type of research would be undertaken and who would be doing the research. Participants were most concerned with genomics data sharing that could lead to discrimination (insurance and employment), data being used for marketing, data security, or commercial use.

Conclusions
Most participants were willing to share their genomic data from medical records with researchers, as long as permission for use was sought. However, the existing policies related to this process in Queensland do not reflect participant expectations for how this is achieved, particularly with anonymous genomics data. This inconsistency may be addressed by process changes, such as inclusion of research in addition to clinical consent or general research data consent programs.
Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study
Authors: Auger Nathalie , Paradis Gilles , Low Nancy , Ayoub Aimina , He Siyi , Potter Brian J. 
Published: November 2020

Abstract
Background
Cannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women.

Methods
We analyzed a longitudinal cohort of 1,247,035 pregnant women in Quebec, Canada, between 1989 and 2019. The main exposure was current or past history of cannabis use disorders at cohort entry. The main outcome measure included future hospital admission for any cardiovascular disorder during 18,998,986 person years of follow-up. We used Cox proportional hazards regression models adjusted for patient characteristics to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of cannabis use disorder with the later risk of cardiovascular hospitalization.

Results
Women with cannabis use disorders had a higher incidence of cardiovascular hospitalization than unexposed women (58.4 vs. 33.6 per 10,000 person years). Cannabis use disorder was associated with 1.48 times the risk of cardiovascular hospitalization (95% CI 1.27–1.72), compared with no cannabis use disorder. The association was greater for cannabis with concomitant use of other substances (HR 1.84, 95% CI 1.53–2.21) than for cannabis alone (HR 1.30, 95% CI 0.99–1.72). Cannabis use disorder was strongly associated with hemorrhagic stroke, even with adjustment for other substance use (HR 2.08, CI 1.07–4.05).

Conclusions
Cannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.
Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs
Authors: Burnett Thomas , Mozgunov Pavel , Pallmann Philip , Villar Sofia S. , Wheeler Graham M. , Jaki Thomas 
Published: November 2020

AbstractAdaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. Despite much research in the statistical literature highlighting the potential advantages of adaptive designs over traditional fixed designs, the uptake of such methods in clinical research has been slow. One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.
Molecular characterization of isolated infectious bronchitis viruses from affected vaccinated broiler flocks in Syria
Authors: Al-Jallad Tamara , Kassouha Morshed , Salhab Mohamad , Alomar Anouar , AL-Masalma Mouhamad , Abdelaziz Fahim 
Published: November 2020

Abstract
Background
Avian Infectious Bronchitis Virus (IBV) is a highly contagious disease that imposes a huge economic burden on the global poultry industry. IBV contains numerous serotypes and variants with incomplete tenuous cross immunological protection. The failure of currently used vaccines to protect against diverse, circulating IBV strains that are specific to a given region poses a major problem for the poultry industry. Thus, there is an urgent need to conduct studies aimed at genotyping field IB viruses. In this study, we have determined the molecular characteristics of circulating IBV by sequencing the S1 gene of viral isolates from affected previously vaccinated broiler flocks suffering from the disease.

Results
Ten isolates propagated in embryonated eggs showed an ability to induce typical IBV lesions after three successive viral passages. We performed a nested RT–PCR assay that targeted the hypervariable region 3 (HVR-3) of the S1 gene, and identified the isolates as IBV through sequence analysis. The IBV isolates showed sequence similarity between the Syrian isolates that vary from 96.20 to 100%, and those being closer to the Variant-2 strain IS/1494/06 (EU780077.2) with 97.5 to 99.4% similarities. However, less nucleotide identity was found with sequences belonging to the used vaccine strains such as H120, Mass5, and 4/91.

Conclusions
This study showed the presence of the Variant-2 strain circulating in Syrian broiler flocks showing signs of IBV disease. Currently, there is no commercial effective vaccine which protects birds against the Variant-2 strain. Continuous monitoring procedures should be taken to control and limit the spread of the IBV Variant-2 strain. This research emphasizes both the importance of epidemiological monitoring in intensive poultry farming for novel pathogens and the use of local isolates as future vaccine targets.
Treatment-related biomarkers in pulmonary hypertension patients on oral therapies
Authors: Swaminathan Aparna C. , Zhu Hongmei , Tapson Victor , Lokhnygina Yuliya , Poms Abby , Kelleher Zach , Gaspard Elijah , Kennedy Karla , Fee Brian E. , Fortin Terry , Mason S. Nicholas , Parikh Kishan , McMahon Tim J. 
Published: November 2020

Abstract
Background
Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.

Methods
This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis.

Results
The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (25.9%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p = 0.03 respectively), and ET-1 predicted future 6MWD (p = 0.02). ET-1 (p = 0.01) and cGMP/NT-proBNP ratio (p = 0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p = 0.03) and PAH patients on ERA therapy (p = 0.01).

Conclusions
ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.
CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR-584-5p
Authors: Zhang Yanhe , Wang Hui , Li Chao , Gao Linlin , Zheng Yayun , Chang Wenjuan , Lu Chao , Zhao Xiaoguang 
Published: November 2020

AbstractBackgroundThere is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism.MethodsThe expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay andSpearmancorrelation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells.ResultsCircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC.ConclusionCircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.
The quality of dietary carbohydrate and fat is associated with better metabolic control in persons with type 1 and type 2 diabetes
Authors: Jacobsen Sabine S. , Vistisen Dorte , Vilsbøll Tina , Bruun Jens M. , Ewers Bettina 
Published: November 2020

Abstract
Background
Diet quality is generally poor in persons with diabetes and it is unknown whether this is associated with worse glycaemic control and atherogenic lipid profile. The aim was to examine diet quality in relation to important markers of metabolic control in adults with type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods
The study was cross-sectional and included 423 (49% females) persons with T1D and 339 (29% females) persons with T2D recruited from an outpatient diabetes clinic in Denmark. Data were collected from July 2014 to January 2015. Diet quality was assessed with a food frequency questionnaire to examine eight key dietary components (carbohydrates, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, added sugar, dietary fibre, fruit and vegetables). Clinical data assessing metabolic control (haemoglobin A1c (HbA1c), total cholesterol (total C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure and body mass index were extracted from the electronic medical records.

Results
In T1D, higher intake of carbohydrates and added sugar was associated with higher HbA1c; higher fruit intake was associated with lower total C and LDL-C; and higher intake of carbohydrates and dietary fibre was associated with lower HDL-C. In T2D, higher intake of saturated fat was associated with higher total C; higher intake of added sugar was associated with higher LDL-C; and higher intake of polyunsaturated fat was associated with higher diastolic blood pressure.

Conclusions
In Danish adults with T1D and T2D, both the total intake and the quality of carbohydrates and fat were associated with an unfavourable glucose regulation and lipid profile. Thus, our findings support a constant focus on diet and emphasise the need for dietary support in people with diabetes to improve diet quality, metabolic control and possibly reduce cardiovascular risk.
Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy
Authors: Sheta Razan , Bachvarova Magdalena , Plante Marie , Renaud Marie-Claude , Sebastianelli Alexandra , Gregoire Jean , Navarro Jamilet Miranda , Perez Ricardo Bringas , Masson Jean-Yves , Bachvarov Dimcho 
Published: November 2020

Abstract
Background
Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as “BRCAness”. Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified.

Methods
We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids.

Results
The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%–60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples.

Conclusion
The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial.
Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination
Authors: Frasca Daniela , Blomberg Bonnie B. 
Published: November 2020

Abstract
Background
Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results
Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure antibody titers, due to a previous infection or vaccination, have less probability to get infected. Examples of this exception are the elderly individuals infected during the 2009 pandemic season who made antibodies with broader epitope recognition and higher avidity than those made by younger individuals. Several studies have allowed the identification of B cell intrinsic defects accounting for sub-optimal antibody responses of elderly individuals. These defects include 1) reduced class switch recombination, responsible for the generation of a secondary response of class switched antibodies, 2) reduced de novo somatic hypermutation of the antibody variable region, 3) reduced binding and neutralization capacity, as well as binding specificity, of the secreted antibodies, 4) increased epigenetic modifications that are associated with lower antibody responses, 5) increased frequencies of inflammatory B cell subsets, and 6) shorter telomeres.

Conclusions
Although influenza vaccination represents the most effective way to prevent influenza infection, vaccines with greater immunogenicity are needed to improve the response of elderly individuals. Recent advances in technology have made possible a broad approach to better understand the age-associated changes in immune cells, needed to design tailored vaccines and effective therapeutic strategies that will be able to improve the immune response of vulnerable individuals.