bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does this lung nodule need urgent review? A discrete choice experiment of Australian general practitioners
Authors: Brownell P. , Piccolo F. , Brims F. , Norman R. , Manners D. 
Published: January 2020

Abstract
Background
Lung cancer is the leading cause of cancer mortality in Australia. Guidelines suggest that patients with suspected lung cancer on thoracic imaging be referred for urgent specialist review. However, the term “suspected” is broad and includes the common finding of lung nodules, which often require periodic surveillance rather than urgent invasive investigation. The British Thoracic Society recommends that a lung nodule with a PanCan risk > 10% be considered for invasive investigation. This study aimed to assess which factors influence general practitioners (GPs) to request urgent review for a lung nodule and if these factors concur with PanCan risk prediction model variables.

Methods
A discrete choice experiment was developed that produced 32 individual case vignettes. Each vignette contained eight variables, four of which form the parsimonious PanCan risk prediction model. Two additional vignettes were created that addressed haemoptysis with a normal chest computed tomography (CT) scan and isolated mediastinal lymphadenopathy. The survey was distributed to 4160 randomly selected Australian GPs and they were asked if the patients in the vignettes required urgent (less than two weeks) specialist review. Multivariate logistic regression identified factors associated with request for urgent review.

Results
Completed surveys were received from 3.7% of participants, providing 152 surveys (1216 case vignettes) for analysis. The factors associated with request for urgent review were nodule spiculation (adj-OR 5.57, 95% CI 3.88–7.99, p < 0.0001), larger nodule size, presentation with haemoptysis (adj-OR 4.79, 95% CI 3.05–7.52, p < 0.0001) or weight loss (adj-OR 4.87, 95% CI 3.13–7.59, p < 0.0001), recommendation for urgent review by the reporting radiologist (adj-OR 4.68, 95% CI 2.86–7.65, p < 0.0001) and female GP gender (adj-OR 1.87, 95% CI 1.36–2.56, p 0.0001). In low risk lung nodules (PanCan risk < 10%), there was significant variability in perceived sense of urgency. Most GPs (83%) felt that a patient with haemoptysis and a normal chest CT scan did not require urgent specialist review but that a patient with isolated mediastinal lymphadenopathy did (75%).

Conclusion
Future lung cancer investigation pathways may benefit from the addition of a risk prediction m9odel to reduce variations in referral behavior for low risk lung nodules.
Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis
Authors: Yoshikawa Takumi , Otsuka Mitsuo , Chiba Hirofumi , Ikeda Kimiyuki , Mori Yuki , Umeda Yasuaki , Nishikiori Hirotaka , Kuronuma Koji , Takahashi Hiroki 
Published: January 2020

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF.

Methods
We retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group.

Results
Forty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months − 6.0% vs 16.7%, 6 months − 10.2% vs 20.2%, KL-6: 3 months − 9.2% vs 6.7%, 6 months − 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = − 0.46 and r = − 0.39, p < 0.01, respectively) and %DLco (r = − 0.67 and r = − 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively).

Conclusions
Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.
Effect of air-polishing on surface roughness of composite dental restorative material – comparison of three different air-polishing powders
Authors: Janiszewska-Olszowska Joanna , Drozdzik Agnieszka , Tandecka Katarzyna , Grocholewicz Katarzyna 
Published: January 2020

Abstract
Background
Increased composite roughness enhances bacterial adhesion and discoloration, thus increasing the risk of gingival inflammation and secondary caries. Concerns about detrimental effects of sodium bicarbonate on surface roughness influenced the development of less abrasive powders: a glycine-based powder and an erythritol-based powder, additionally - sodium bicarbonate-based powder of reduced grain size. However, there is limited evidence on effects of these materials on the surface of dental fillings. The aim of the present study was to compare the effects of three air-polishing powders (of a reduced abrasiveness) on surface roughness of microhybrid restorative composite material.

Material and methods
Microhybrid light-cure resin composite samples were placed on 64 plaster cubes and light-cured through polyester strips. Surface roughness was measured using laser confocal microscope (magnification 2160x). The specimens were randomly divided into three groups (n = 20, 20 and 24) and air-polished with: sodium bicarbonate (40 μm), glycine (25 μm) and erythritol (14 μm), respectively. Then surface roughness was remeasured, keeping the same field of observation. Specialized 3D analysis software was used for data processing. Parameters according to ISO 25178: Sa, Sq, Sku, Sp, Sv, Sz, Ssk were used to describe surface roughness.

Results
Sa, Sq, Sp, Sv, Sz increased significantly following air polishing. Ssk was significantly higher, whereas Sku was significantly lower in sodium bicarbonate and erythritol groups than before air polishing. Comparison between the three powders revealed that Sa was significantly higher in sodium bicarbonate group than in glycine group. Sku was significantly higher in glycine and erythritol groups than in sodium bicarbonate group.

Conclusions
Sodium bicarbonate has a stronger detrimental effect on composite surface than glycine or erythritol. No advantage of erythritol comparing to glycine could be found.
Association between water, sanitation, general hygiene and oral hygiene practices of street-involved young people in Southwest Nigeria
Authors: Folayan Morenike Oluwatoyin , Obiyan Mary O. , Olaleye Atinuke O. 
Published: January 2020

AbstractBackgroundOral hygiene practices can be linked to personal hygiene practices, including access to water and other sanitation facilities. The objective of the study was to determine if there is an association between oral hygiene practices and water and sanitation hygiene (WASH) practices among street-involved young people (SIYP).MethodsA cross-sectional study recruited SIYP age 10–24 years in two States in Nigeria recruited through respondent-driven sampling in December 2018. Interviewer-administered questionnaires were used to collect data on water access, sanitation, personal and oral hygiene. The instruments used for collecting the data were standardized tools for measuring the phenomena studied. The association between knowledge and practice of oral hygiene; oral hygiene and water, sanitation and hygiene (WASH); and indicators of good oral hygiene were determined using binary logistic regression guided by two models.ResultsA total of 845 study participants were recruited. The proportion of SIYP with good knowledge of oral hygiene was low (31.2%), and fewer had good oral hygiene practice (8.9%). There were significant associations between knowledge and practice of tooth cleaning, use of fluoride-containing toothpaste, dental flossing, consumption of sugar between meals, and frequency of dental check-ups (p < 0.001 respectively). Respondents with good water collection and storage practices (AOR: 2.01; 95% CI: 1.24–3.24;P = 0.005) and those residing in Lagos (AOR: 2.85; 95% CI: 1.61–5.06;P = 0.001) had a higher likelihood of having good oral hygiene.ConclusionGood oral hygiene practices of SIYP in Nigeria is associated with access to water collection and storage. WASH programs can have an impact on health through improved oral hygiene practices.
Zhenqing recipe attenuates non-alcoholic fatty liver disease by regulating the SIK1/CRTC2 signaling in experimental diabetic rats
Authors: Song Daofei , Yin Lei , Wang Chang , Wen Xiuying 
Published: January 2020

Abstract
Background
As a compound Chinese medicine, Zhenqing Recipe (ZQR) has been shown to ameliorate hyperglycemia, hyperlipidemia, fatty liver and insulin resistance in patients with diabetes and diabetic rats. In this paper, we further examined the effect of ZQR on diabetes complicated by non-alcoholic fatty liver disease (NAFLD) and the underlying molecular mechanisms.

Methods
Diabetic rats with NAFLD were developed by a high-fat diet (HFD) with low-dose streptozotocin (STZ) injection for 4 weeks. These rats were randomly separated into the diabetic model (DM), ZQR, metformin (Met), adenovirus expressing-salt-induced kinase 1 (Ad-SIK1) and adenovirus labeled with green fluorescent protein (Ad-GFP) groups. The effects on hepatic expression of gluconeogenic genes, glycolipid metabolism and pathological changes were subsequently detected.

Results
Serum glucose, triglycerides (TG), total cholesterol (TC) and hepatic TG were reduced in the ZQR group. The histopathological and immunohistochemical changes in the liver and pancreas in the ZQR group were significantly alleviated. The decrease of SIK1 expression was observed in the liver of diabetic rats induced by HFD and STZ. SIK1 overexpression in the liver relieved hyperglycemia, hyperlipidemia and fatty liver. Both the mRNA and protein levels of CREB-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the liver were drastically reduced, whereas those of SIK1 were markedly increased in the ZQR group compared to levels in the DM group. Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.

Conclusions
ZQR ameliorates hepatic gluconeogenesis and lipid storage in diabetic rats induced by HFD and STZ by activating the SIK1/CRTC2 signaling pathway. Upregulating hepatic SIK1 by ZQR may represent an efficient strategy for treating diabetes with NAFLD.
Health-related quality of life and symptoms in patients with IPF treated with nintedanib: analyses of patient-reported outcomes from the INPULSIS® trials
Authors: Kreuter Michael , Wuyts Wim A. , Wijsenbeek Marlies , Bajwah Sabrina , Maher Toby M. , Stowasser Susanne , Male Natalia , Stansen Wibke , Schoof Nils , Orsatti Leticia , Swigris Jeffrey 
Published: January 2020

Abstract
Background
In the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George’s respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression.

Methods
Patient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DLCO] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test.

Results
Data from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DLCO ≤ 40%, CPI >  45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores).

Conclusions
In patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.
Using a ‘rich picture’ to facilitate systems thinking in research coproduction
Authors: Conte Kathleen P. , Davidson Seanna 
Published: January 2020

Abstract
Background
In coproduction research, traditional ‘end-users’ are involved in the entire research process. The aim is to facilitate research translation by improving the timeliness and relevance of research. Because end-users often come from multiple sectors and hold diverse perspectives and priorities, involving them in coproduction can be challenging. Tools and approaches are needed to support coproduction teams to successfully navigate divergent viewpoints while producing rigorous but meaningful research outcomes. Rich pictures are a systems thinking tool to help make sense of complexity. In this paper, we describe how we developed and applied a ‘rich picture’ in a coproduction project with policy-level partners.

Methods
Guided by systems thinking principles, we conducted a systemic analysis of ethnographic fieldnotes collected as part of a broader study that examined the dynamics between an IT system and the implementation of the state-wide childhood obesity prevention programmes it was designed to monitor. Translating qualitative themes into metaphor and imagery, we created a visual depiction of the system to reflect the experience of the system’s users (health promotion practitioners) and facilitated a workshop with policy-level programme administrators (i.e. participants, n = 7). Our aim was to increase the transparency of the system for our research partners and to spark new insights to improve the quality of programme implementation.

Results
Guided by provocative questions, participants discussed and challenged each other’s thinking on the current functioning of the system. They identified future lines of inquiry to explore for quality improvement. Participants strongly agreed that the picture was a constructive way to engage with the ethnographic data but were challenged by the information and its implications. The opportunity for participants to co-learn from each other as well as from the picture was an added value.

Conclusion
In the context of the facilitated workshop, the rich picture enabled research partners to engage with complex research findings and gain new insights. Its value was harnessed via the guided participatory process. This demonstrates the importance that, in the future, such tools should be accompanied by practices that enable participants to think with and apply systems thinking concepts and principles.
Safety, tolerability and immunogenicity of V934/V935 hTERT vaccination in cancer patients with selected solid tumors: a phase I study
Authors: Aurisicchio Luigi , Fridman Arthur , Mauro David , Sheloditna Rose , Chiappori Alberto , Bagchi Ansuman , Ciliberto Gennaro 
Published: January 2020

Abstract
Background
Human telomerase reverse transcriptase (hTERT) is an antigen that may represent a target for a novel anti-cancer strategy. A pilot, phase I study tested the safety and feasibility of a prime-boost immunization regimen based on V935, an adenoviral type 6 vector vaccine expressing a modified version of hTERT, administered alone or in combination with V934, a DNA plasmid that also expresses the same antigen and is delivered using the electroporation injection technique.

Methods
Treatments: Group #1 received two doses (low-dose: 0.5 × 109 vg, and high-dose: 0.5 × 1011 vg) of V935 followed by a 4-week observation period. Group #2 received three doses of V934-electroporation and two doses of V935 following a 4-week observation period. Doses were low-dose V934 (0.25 mg of plasmid) with low-dose V935 (0.5 × 109 vg); high-dose V934 (2.5 mg of plasmid) with high-dose V935 (0.5 × 1011 vg). Group #3 received five doses of V934-EP and two doses of V935: V934 was administered IM every 2 weeks for five doses. Following a 4-week observation period, V935 was administered IM every 2 weeks for two doses followed by a 4-week observation period. One (1) dose level was tested in treatment group #3: high-dose V934 (2.5 mg of plasmid), in combination with high-dose V935 (0.5 × 1011 vg). Immunogenicity was measured by ELISPOT assay and three pools of peptides encompassing the sequence of hTERT.

Results
In total, 37 patients affected by solid tumors (prostate cancer in 38%) were enrolled. The safety profile of different regimens was good and comparable across groups, with no severe adverse events, dose-limiting toxicities or treatment discontinuations. As expected, the most common adverse events were local reactions. A significant increase in ELISPOT responses against hTERT peptide pool 2 was observed (p < 0.01), while no evidence of boosting was observed for peptide pools 1 and 3. This was also evident for group #1 and #2 separately. In patients with prostate cancer, there was a significant increase in ELISPOT response against hTERT peptide pool 2 following immunization (p < 0.01), regardless of previous therapy, immunosuppressing agents, or adenoviral type 6 titers at screening.

Conclusion
Our results suggest the safety and feasibility of V934/V935 hTERT vaccination in cancer patients with solid tumors
Trial Registration Name of the registry: ClinicalTrial.gov Trial registration number: NCT00753415 Date of registration: 16 September 2008 Retrospectively registered URL of trial registry record: https://clinicaltrials.gov/ct2/results?cond=&term=NCT00753415&cntry=&state=&city=&dist=
Improved therapeutics of modified mesenchymal stem cells: an update
Authors: Ocansey Dickson Kofi Wiredu , Pei Bing , Yan Yongmin , Qian Hui , Zhang Xu , Xu Wenrong , Mao Fei 
Published: January 2020

Abstract
Background
Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo.

Body
In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated.

Conclusion
The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.