bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring patient-reported barriers to advance care planning in family practice
Authors: Bernard Carrie , Tan Amy , Slaven Marissa , Elston Dawn , Heyland Daren K. , Howard Michelle 
Published: May 2020

Abstract
Background
Although patient-centred care has become increasingly important across all medical specialties, when it comes to end of life care, research has shown that treatments ordered are not often concordant with people’s expressed preferences. Patient and family engagement in Advance Care Planning (ACP) in the primary care setting could improve the concordance between patients’ wishes and the healthcare received when patients cannot speak for themselves. The aim of this study was to better understand the barriers faced by older patients regarding talking to their family members and family physicians about ACP.

Methods
In this multi-site cross-sectional study, three free text questions regarding reasons patients found it difficult to discuss ACP with their families or their family physicians were part of a self-administered questionnaire about patients’ knowledge of and engagement in ACP. The questionnaire, which included closed ended questions followed by three probing open ended questions, was distributed in 20 family practices across 3 provinces in Canada. The free text responses were analyzed using thematic analysis and form the basis of this paper.

Results
One hundred two participants provided an analyzable response to the survey when asked why they haven’t talked to someone about ACP. Two hundred fifty-four answered the question about talking to their physician and 340 answered the question about talking to family members. Eight distinct themes emerged from the free text response analysis: 1. They were too young for ACP; 2. The topic is too emotional; 3. The Medical Doctor (MD) should be responsible for bringing up ACP 4. A fear of negatively impacting the patient-physician relationship; 5. Not enough time in appointments; 6. Concern about family dynamics; 7. It’s not a priority; and 8. A lack of knowledge about ACP.

Conclusions
Patients in our sample described many barriers to ACP discussions, including concerns about the effect these discussions may have on relationships with both family members and family physicians, and issues relating to patients’ knowledge and interpretation of the importance, responsibility for, or relevance of ACP itself. Family physicians may be uniquely placed to leverage the longitudinal, person- centred relationship they have with patients to mitigate some of these barriers.
Knowledge and practices of primary care physicians or general practitioners treating post-infectious Irritable Bowel Syndrome
Authors: Austhof Erika , Schaefer Kenzie , Faulkner Jaime , Bach Laura , Riddle Mark , Pogreba-Brown Kristen 
Published: May 2020

Abstract
Background
Post-infectious Irritable Bowel Syndrome (PI-IBS) is a functional bowel disorder which has significant impacts to a patient’s quality of life. No IBS-specific biomarker or treatment regimen for PI-IBS currently exists, therefore understanding practice patterns and variance is of interest.

Methods
This online survey of primary care physicians and general practitioners in the USA aimed to understand the knowledge and treatment of PI-IBS within the physician’s current practice. Summary statistics are provided with a commentary on implications for practices and treatment of PI-IBS.

Results
Most physician survey respondents (n = 50) were aware of PI-IBS, but less than half discussed this condition as a possible outcome in their patients with a recent gastrointestinal infection. Most physicians indicated that they would treat the patients themselves with a focus on managing IBS through different treatment modalities based on severity. Treatment for PI-IBS followed IBS recommendations, but most physicians also prescribed a probiotic for therapy. Physicians estimated that 4 out of 10 patients who develop PI-IBS will have life-long symptoms and described significant impacts to their patient’s quality of life. Additionally, physicians estimated a significant financial burden for PI-IBS patients, ranging from $100–1000 (USD) over the course of their illness. Most physicians agreed that they would use a risk score to predict the probability of their patients developing PI-IBS, if available.

Conclusions
While this survey is limited due to sample size, physician knowledge and treatment of PI-IBS was consistent across respondents. Overall, the physicians identified significant impacts to patient’s quality of life due to PI-IBS.
Impact of hemodialysis and post-dialysis period on granular activity levels
Authors:   For the HDFIT Study Investigators, Larkin John W. , Han Maggie , Han Hao , Guedes Murilo H. , Gonçalves Priscila Bezerra , Poli-de-Figueiredo Carlos Eduardo , Cuvello-Neto Américo Lourenço , Barra Ana Beatriz L. , de Moraes Thyago Proença , Usvyat Len A. , Kotanko Peter , Canziani Maria Eugenia F. , Raimann Jochen G. , Pecoits-Filho Roberto 
Published: May 2020

Abstract
Background
Physical activity (PA) is typically lower on hemodialysis (HD) days. Albeit intradialytic inactivity is expected, it is unknown whether recovery after HD contributes to low PA. We investigated the impact of HD and post-HD period on granular PA relative to HD timing.

Methods
We used baseline data from the HDFIT trial conducted from August 2016 to October 2017. Accelerometry measured PA over 1 week in patients who received thrice-weekly high-flux HD (vintage 3 to 24 months), were clinically stable, and had no ambulatory limitations. PA was assessed on HD days (0 to ≤24 h after start HD), first non-HD days (> 24 to ≤48 h after start HD) and second non-HD day (> 48 to ≤72 h after start HD). PA was recorded in blocks/slices: 4 h during HD, 0 to ≤2 h post-HD (30 min slices), and > 2 to ≤20 h post-HD (4.5 h slices). Blocks/slices of PA were captured at concurrent/parallel times on first/second non-HD days compared to HD days.

Results
Among 195 patients (mean age 53 ± 15 years, 71% male), step counts per 24-h were 3919 ± 2899 on HD days, 5308 ± 3131 on first non-HD days (p < 0.001), and 4926 ± 3413 on second non-HD days (p = 0.032). During concurrent/parallel times to HD on first and second non-HD days, patients took 1308 and 1128 more steps (both p < 0.001). Patients took 276 more steps and had highest rates of steps/hour 2-h post-HD versus same times on first non-HD days (all p < 0.05). Consistent findings were observed on second non-HD days.

Conclusions
PA was higher within 2-h of HD versus same times on non-HD days. Lower PA on HD days was attributable to intradialytic inactivity. The established PA profiles are of importance to the design and development of exercise programs that aim to increase activity during and between HD treatments.

Trial registration
HDFIT was prospectively registered 20 April 2016 on ClinicalTrials.gov (NCT02787161)
Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer
Authors: Singleton Dean C. , Dechaume Anne-Lise , Murray Pamela M. , Katt William P. , Baguley Bruce C. , Leung Euphemia Y. 
Published: May 2020

Abstract
Background
Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle intermediates. CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase that has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients.

Methods
A panel of eleven breast cancer cell lines was used to investigate the anti-proliferative effects of the glutaminase inhibitors CB-839 and BPTES in different types of culture medium, with or without additional pyruvate supplementation. The abundance of the TCA cycle intermediate fumarate was quantified as a measure if TCA cycle anaplerosis. Pyruvate secretion by TNBC cultures was then assessed with or without AZD3965, a monocarboxylate transporter 1 (MCT1) inhibitor. Finally, two dimensional (2D) monolayer and three dimensional (3D) spheroid assays were used to compare the effect of microenvironmental growth conditions on CB-839 activity.

Results
The anti-proliferative activity of CB-839 in a panel of breast cancer cell lines was similar to published reports, but with a major caveat; growth inhibition by CB-839 was strongly attenuated in culture medium containing pyruvate. This pyruvate-dependent attenuation was also observed with a related glutaminase inhibitor, BPTES. Studies demonstrated that exogenous pyruvate acted as an anaplerotic substrate preventing the decrease of fumarate in CB-839-treated conditions. Furthermore, endogenously produced pyruvate secreted by TNBC cell lines was able to act in a paracrine manner to significantly decrease the sensitivity of recipient cells to glutaminase inhibition. Suppression of pyruvate secretion using the MCT1 inhibitor AZD3965, antagonised this paracrine effect and increased CB-839 activity. Finally, CB-839 activity was significantly compromised in 3D compared with 2D TNBC culture models, suggesting that 3D microenvironmental features impair glutaminase inhibitor responsiveness.

Conclusion
This study highlights the potential influence that both circulating and tumour-derived pyruvate can have on glutaminase inhibitor efficacy. Furthermore, it highlights the benefits of 3D spheroid cultures to model the features of the tumour microenvironment and improve the in vitro investigation of cancer metabolism-targeted therapeutics.
Independence of HIF1a and androgen signaling pathways in prostate cancer
Authors: Tran Maxine G. B. , Bibby Becky A. S. , Yang Lingjian , Lo Franklin , Warren Anne Y. , Shukla Deepa , Osborne Michelle , Hadfield James , Carroll Thomas , Stark Rory , Scott Helen , Ramos-Montoya Antonio , Massie Charlie , Maxwell Patrick , West Catharine M. L. , Mills Ian G. , Neal David E. 
Published: May 2020

Abstract
Background
Therapeutic targeting of the androgen signaling pathway is a mainstay treatment for prostate cancer. Although initially effective, resistance to androgen targeted therapies develops followed by disease progression to castrate-resistant prostate cancer (CRPC). Hypoxia and HIF1a have been implicated in the development of resistance to androgen targeted therapies and progression to CRCP. The interplay between the androgen and hypoxia/HIF1a signaling axes was investigated.

Methods
In vitro stable expression of HIF1a was established in the LNCaP cell line by physiological induction or retroviral transduction. Tumor xenografts with stable expression of HIF1a were established in castrated and non-castrated mouse models. Gene expression analysis identified transcriptional changes in response to androgen treatment, hypoxia and HIF1a. The binding sites of the AR and HIF transcription factors were identified using ChIP-seq.

Results
Androgen and HIF1a signaling promoted proliferation in vitro and enhanced tumor growth in vivo. The stable expression of HIF1a in vivo restored tumor growth in the absence of endogenous androgens. Hypoxia reduced AR binding sites whereas HIF binding sites were increased with androgen treatment under hypoxia. Gene expression analysis identified seven genes that were upregulated both by AR and HIF1a, of which six were prognostic.

Conclusions
The oncogenic AR, hypoxia and HIF1a pathways support prostate cancer development through independent signaling pathways and transcriptomic profiles. AR and hypoxia/HIF1a signaling pathways independently promote prostate cancer progression and therapeutic targeting of both pathways simultaneously is warranted.
CYP and SXR gene polymorphisms influence in opposite ways acute rejection rate in pediatric patients with renal transplant
Authors: Turolo Stefano , Edefonti Alberto , Ghio Luciana , Testa Sara , Morello William , Montini Giovanni 
Published: May 2020

Abstract
Background
We evaluated the role of CYP3A5, ABCB1 and SXR gene polymorphisms in the occurrence of acute kidney rejection in a cohort of pediatric renal transplant recipients.

Methods
Forty-nine patients were genotyped for CYP3A5, ABCB1 and SXR polymorphisms and evaluated with tacrolimus through levels in a retrospective monocenter study.

Results
Patients with the A allele of CYP3A5 treated with tacrolimus had a higher risk of acute rejection than those without the A allele, while patients carrying the homozygous GG variant for SXR A7635GG did not show any episode of acute rejection.

Conclusion
Genetic analysis of polymorphisms implicated in drug metabolism and tacrolimus trough levels may help to forecast the risk of acute rejection and individualize drug dosage in children undergoing renal transplantation.
Incidence and risk factors of spinal epidural hemorrhage after spine surgery: a cross-sectional retrospective analysis of a national database
Authors: Park Ji Hyun , Park Sunny , Choi Soo An 
Published: May 2020

Abstract
Background
With increasing number of patients undergoing spine surgery, the spinal epidural hemorrhage (SEH) has become a growing concern. However, current studies on SEH rely on case reports or observations from a single center. Our study attempted to demonstrate the incidence rate and risk factors of SEH using a national dataset.

Methods
A total of 17,549 spine surgery cases from the Health Insurance Review and Assessment Service National Inpatient Sample of 2014 were analyzed. After evaluating the incidence of SEH based on severe cases requiring reoperation, a univariate comparison was performed. Variables found to be significant were included in a multivariable analysis model to determine the risk factors.

Results
The incidence of SEH was found to be 1.15% in Korean population, and there were no severe SEH cases. Our analysis confirmed the previous findings that lumbar surgery, intraoperative blood loss, prolonged surgical time, high blood pressure, use of nonsteroidal anti-inflammatory drugs, and concurrent bleeding factors are the risk factors of SEH. Anterior approach showed a protective effect. The use of anticoagulant demonstrated no statistical significance.

Conclusion
Although severe SEH cases were not detected, the incidence of SEH was similar to that reported in literature. Given that SEH is a rare complication of spine surgery and constitutes an important research area that needs to be studied further, our study makes a meaningful contribution based on a rigorous national level sample for the first time and provides the academic circle and health professionals with a reliable evidence of improved clinical outcomes in such cases.
Risk assessment for prolonged sickness absence due to musculoskeletal disorders: protocol for a prospective cohort study
Authors: Tveter Anne Therese , Øiestad Britt Elin , Rysstad Tarjei Langseth , Aanesen Fiona , Tingulstad Alexander , Småstuen Milada Cvancarova , Grotle Margreth 
Published: May 2020

Abstract
Background
Musculoskeletal disorders are the leading cause of sickness absence and disability pension in Norway. There is strong evidence that long-term sickness absence due to musculoskeletal disorders are associated with a reduced probability of return to work (RTW). A way to meet the economic and resource-demanding challenges related to individual follow-up of this group is to identify and treat those individuals with a high risk of prolonged sickness. The overall purposes of this project are 1) to determine the most accurate screening tool to identify people at a high risk of prolonged sickness absence due to an musculoskeletal disorder, and 2) to investigate severity of musculoskeletal health, health-related quality-of-life, health care utilization, and costs across different risk profiles in people on sick leave due to a musculoskeletal disorder.

Methods
People older than 18 years of age on sick leave for at least 4 weeks due to a musculoskeletal disorder will be invited to participate in this prospective observational cohort study conducted within the Norwegian Welfare and Labor Administration (NAV) system in collaboration with OsloMet – Oslo Metropolitan University. The main outcome is sickness absence, obtained from the NAV registry. Data on sickness absence will be retrieved prospectively in the period from study inclusion to 12 months follow-up, and retrospectively 12 months before inclusion in the study. Possible risk factors will be self-reported by the participants at inclusion while health care utilization will be retrieved from registry data. To conduct analyses including 15 to 20 predictor variables, we aim at including 500–600 people on sick leave due to musculoskeletal disorders.

Discussion
This study may provide tools that can be used to identify individuals with high risk of prolonged sickness absence and may thus be important from both a socioeconomic and individual perspective. Further, the study may give valuable insight into identification of sickness absence profiles and the associations between these profiles and musculoskeletal health status, health-related quality of life and costs.

Trial registration
Retrospectively registered in ClinicalTrials.gov (NCT04196634, 27.11.2019).
Year-round spatiotemporal distribution pattern of a threatened sea duck species breeding on Kolguev Island, south-eastern Barents Sea
Authors: Karwinkel Thiemo , Pollet Ingrid L. , Vardeh Sandra , Kruckenberg Helmut , Glazov Petr , Loshchagina Julia , Kondratyev Alexander , Merkel Benjamin , Bellebaum Jochen , Quillfeldt Petra 
Published: May 2020

AbstractBackgroundThe long-tailed duck (Clangula hyemalis) was categorized as ´Vulnerable` by the IUCN after a study revealed a rapid wintering population decline of 65% between 1992–1993 and 2007–2009 in the Baltic Sea. As knowledge about the European long-tailed duck’s life cycle and movement ecology is limited, we investigate its year-round spatiotemporal distribution patterns. Specifically, we aimed to identify the wintering grounds, timing of migration and staging of this population via light-level geolocation.ResultsOf the 48 female long-tailed ducks tagged on Kolguev Island (western Russian Arctic), 19 were recaptured to obtain data. After breeding and moulting at freshwater lakes, ducks went out to sea around Kolguev Island and to marine waters ranging from the White Sea to Novaya Zemlya Archipelago for 33 ± 10 days. After a rapid autumn migration, 18 of 19 birds spent their winter in the Baltic Sea and one bird in the White Sea, where they stayed for 212 ± 3 days. There, they used areas known to host long-tailed ducks, but areas differed among individuals. After a rapid spring migration in mid-May, the birds spent 23 ± 3 days at sea in coastal areas between the White Sea and Kolguev Island, before returning to their freshwater breeding habitats in June.ConclusionsThe Baltic Sea represents the most important wintering area for female long-tailed ducks from Kolguev Island. Important spring and autumn staging areas include the Barents Sea and the White Sea. Climate change will render these habitats more exposed to human impacts in the form of fisheries, marine traffic and oil exploitation in near future. Threats that now operate in the wintering areas may thus spread to the higher latitude staging areas and further increase the pressure on long-tailed ducks.
Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer’s disease through a network pharmacology approach
Authors: Qu Yan-Jie , Zhen Rong-Rong , Zhang Li-Min , Gu Chao , Chen Lei , Peng Xiao , Hu Bing , An Hong-Mei 
Published: May 2020

Abstract
Background
Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer’s disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach.

Methods
The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool.

Results
A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and β-sitosterol were obtained from the analysis of the key targets.

Conclusions
Ursolic acid, anethole and β-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.
Standard setting made easy: validating the Equal Z-score (EZ) method for setting cut-score for clinical examinations
Authors: Shulruf Boaz , Yang Ying-Ying , Huang Pin-Hsiang , Yang Ling-Yu , Huang Chin-Chou , Huang Chia-Chang , Liu Chih-Wei , Huang Shiau-Shian , Chen Chen-Huan , Lee Fa-Yauh , Kao Shou-Yen 
Published: May 2020

Abstracts
Background
This study aims to assess the feasibility, reliability and validity of the panel-based Equal Z-score (EZ) method applied to objective structural clinical examination (OSCE) of Chinese medical students and undertaking a comparison with the statistical techniques-based Borderline Regression Method (BRM).

Methods
Data received from two cohorts of 6th and 7th year medical students in Taiwan who set the mock OSCE as a formative assessment. Traditionally this medical school uses BRM to set the pass/fail cut-score. For the current study, 31 OSCE panellists volunteered to participate in the EZ method in parallel to the BRM.

Results
In the conduct of this study, each panel completed this task for an OSCE exam comprising 12 stations within less than 60 min. Moreover, none of the 31 panellists, whose are busy clinicians, had indicated that the task was too difficult or too time-consuming. Although EZ method yielded higher cut-scores than the BRM it was found reliable. Intraclass correlation (ICC) measuring absolute agreement, across the three groups of panellists was .893 and .937 for the first and second rounds respectively, demonstrating high level of agreement across groups with the EZ method and the alignment between the BRM and the EZ method was visually observed. The paired t-test results identified smaller differences between the cut-scores within methods than across methods.

Conclusions
Overall this study suggests that the EZ method is a feasible, reliable and valid standard setting method. The EZ method requires relatively little resources (takes about an hour to assess a 12 station OSCE); the calculation of the cut-score is simple and requires basic statistical skills; it is highly reliable even when only 10 panellists participate in the process; and its validity is supported by comparison to BRM. This study suggests that the EZ method is a feasible, reliable and valid standard setting method.