bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of SIGN glaucoma guidelines on false-positive referrals from community optometrists in Central Scotland
Authors: Sii Samantha , Nasser Ahmad , Loo Cheng Yi , Croghan Catherine , Rotchford Alan , Agarwal Pankaj Kumar 
Published: May 2018

Background
Since the introduction of National Institute for Health and Care Excellence glaucoma guidelines 2009, the number of referrals from community optometrists to hospital eye services has increased across the UK, resulting in increase in first visit discharge rates (FVDRs).

Aim
To assess the impact of Scottish Intercollegiate Guidelines Network (SIGN) 144 on quality of referrals from community optometrists.

Methodology
A retrospective study of patient records who attended as new adult glaucoma referrals to clinics in Princess Alexandra Eye Pavilion, Edinburgh, and in Greater Glasgow and Clyde, was carried out across October–November 2014 (group 1) and September–October 2016 (group 2), before and after the introduction of SIGN 144. The primary outcome of this study is FVDRs. A secondary outcome is the extent of compliance to referral recommendations by SIGN guidelines.

Results

Three hundred and twelve and 325 patients were included in groups 1 and 2, respectively. There was a significant decline in FVDRs between these two periods from 29.2% to 19.2%.
(
p=
0.004) (OR 0.58 (95%CI 0.40 to 0.84)). Post-SIGN guidelines, 87% of referrals were compliant to SIGN referral criteria while 13% remained non-compliant. The main reasons for non-compliance were no repeatable visual field defects (42.0%) and referrals due to high intraocular pressure were either not repeated or not interpreted in the context of age and central corneal thickness (36.8%).

Conclusion
Patients referred after the introduction of SIGN guidelines were 33.5% less likely to be discharged at the first visit. Although compliance to most recommendations in SIGN guidelines has improved, there is still a need to improve adherence to referral criteria
Variable effectiveness of stepwise implementation of nudge-type interventions to improve provider compliance with intraoperative low tidal volume ventilation
Authors: O’Reilly-Shah Vikas N , Easton George S , Jabaley Craig S , Lynde Grant C 
Published: May 2018

BackgroundIdentifying mechanisms to improve provider compliance with quality metrics is a common goal across medical disciplines. Nudge interventions are minimally invasive strategies that can influence behavioural changes and are increasingly used within healthcare settings. We hypothesised that nudge interventions may improve provider compliance with lung-protective ventilation (LPV) strategies during general anaesthesia.MethodsWe developed an audit and feedback dashboard that included information on both provider-level and department-level compliance with LPV strategies in two academic hospitals, two non-academic hospitals and two academic surgery centres affiliated with a single healthcare system. Dashboards were emailed to providers four times over the course of the 9-month study. Additionally, the default setting on anaesthesia machines for tidal volume was decreased from 700 mL to 400 mL. Data on surgical cases performed between 1 September 2016 and 31 May 2017 were examined for compliance with LPV. The impact of the interventions was assessed via pairwise logistic regression analysis corrected for multiple comparisons.ResultsA total of 14 793 anaesthesia records were analysed. Absolute compliance rates increased from 59.3% to 87.8%preintervention to postintervention. Introduction of attending physician dashboards resulted in a 41% increase in the odds of compliance (OR 1.41, 95% CI 1.17 to 1.69, p=0.002). Subsequently, the addition of advanced practice provider and resident dashboards lead to an additional 93% increase in the odds of compliance (OR 1.93, 95% CI 1.52 to 2.46, p<0.001). Lastly, modifying ventilator defaults led to a 376% increase in the odds of compliance (OR 3.76, 95% CI 3.1 to 4.57, p<0.001).ConclusionAudit and feedback tools in conjunction with default changes improve provider compliance.
Brock malignancy risk calculator for pulmonary nodules: validation outside a lung cancer screening population
Authors: Chung Kaman , Mets Onno M , Gerke Paul K , Jacobs Colin , den Harder Annemarie M , Scholten Ernst T , Prokop Mathias , de Jong Pim A , van Ginneken Bram , Schaefer-Prokop Cornelia M 
Published: May 2018

ObjectiveTo assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting.MethodsIn two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case–control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model.ResultsAfter the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p<0.001). At 10% malignancy risk, the threshold suggested by the British Thoracic Society, sensitivity of the full model was 75% and 81%, specificity was 85% and 84%, positive predictive values were 14% and 10% at negative predictive value (NPV) of 99%. The optimal threshold was 6% for centre A and 8% for centre B, with NPVs >99%.DiscussionThe Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations.
Response of dry bean to Group 15 herbicides applied preplant incorporated
Authors: Soltani Nader , Shropshire Christy , Sikkema Peter H. 
Published: May 2018

A study consisting of four field experiments was conducted over a 2-yr period (2016, 2017) near Exeter and Ridgetown, ON, to compare the tolerance of adzuki, kidney, small red, and white beans to four Group 15 herbicides including pethoxamid (1200 and 2400 g a.i. ha−1), S-metolachlor (1600 and 3200 g a.i. ha−1), dimethenamid-P (693 and 1386 g a.i. ha−1), and pyroxasulfone (100 and 200 g a.i. ha−1) applied preplant incorporated (PPI). At 1 wk after emergence (WAE), pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone caused as much as 22%, 17%, 38%, and 15% adzuki bean injury, respectively. The injury decreased with time; at 8 WAE, pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone applied PPI caused as much as 3%, 4%, 12%, and 7% adzuki bean injury, respectively. The injury was lower in other market classes of dry bean. At 1, 2, and 4 WAE, pethoxamid, S-metolachlor, dimethenamid-P, and pyroxasulfone caused as much as 4%, 2%, 4%, and 14% injury in kidney bean, 3%, 2%, 4%, and 12% injury in small red bean, and 5%, 3%, 6%, and 13% injury in white bean, respectively. However, the injury at 8 WAE was 5% or less in kidney, small red, and white beans with all Group 15 herbicides evaluated. Based on this research, pyroxasulfone was the most injurious to dry beans, it reduced plant height as much as 15% and seed yield as much as 17%. The Group 15 herbicides evaluated were more injurious to adzuki bean than kidney, small red, or white beans.
Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells
Authors: Kannappan Ramaswamy , Mattapally Saidulu , Wagle Pooja A. , Zhang Jianyi 
Published: May 2018

The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human induced pluripotent stem cells (hiPSCs) has never been studied. p53-TAD was knocked out in iPSCs using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD knockout (KO) cells were characterized by accelerated proliferation, decreased population doubling time, and unaltered Bcl-2, Bcl-2-binding component 3, insulin-like growth factor 1 receptor, and Bax and altered Mdm2, p21, and p53-induced death domain transcript expression. In p53-TAD KO cells, the p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 expression were found to be reduced compared with p53 wild-type cells. Exposure to a low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) as measured by RAD50 and MRE11 expression, checkpoint kinase 2 activation, and γH2A.X recruitment at DNA strand breaks in both cell groups, indicating that silence of p53-TAD does not affect the DDR mechanism upstream of p53. After removal of Doxo, p53 wild-type hiPSCs underwent DNA repair, corrected their damaged DNA, and restored DNA integrity. Conversely, p53-TAD KO hiPSCs did not undergo complete DNA repair and failed to restore DNA integrity. More importantly, continuous culture of p53-TAD KO hiPSCs underwent G2/M cell cycle arrest and expressed the cellular senescent marker p16INK4a. Our data clearly show that silence of the TAD of p53 did not affect DDR but affected the DNA repair process, implying the crucial role of p53-TAD in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent cellular senescence. NEW & NOTEWORTHY The p53 transactivation domain (TAD) in human induced pluripotent stem cells (iPSCs) was deleted using the CRISPR/Cas9 system. Deletion of p53-TAD resulted in increased cell proliferation but did not affect iPSC pluripotency. DNA repair machinery upstream of p53 was not affected in p53-TAD knockout, but p53-regulated DNA repair proteins xeroderma pigmentosum group A, DNA polymerase H, and DNA-binding protein 2 were affected. Finally, p53-TAD was found to be necessary for iPSCs to repair damaged DNA and retain DNA integrity.
The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients
Authors: Zill Oliver A. , Banks Kimberly C. , Fairclough Stephen R. , Mortimer Stefanie A. , Vowles James V. , Mokhtari Reza , Gandara David R. , Mack Philip C. , Odegaard Justin I. , Nagy Rebecca J. , Baca Arthur M. , Eltoukhy Helmy , Chudova Darya I. , Lanman Richard B. , Talasaz AmirAli 
Published: May 2018

AbstractPurpose: Cell-free DNA (cfDNA) sequencing provides a noninvasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants.Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across &gt;50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality.Results: Patterns and prevalence of cfDNA alterations in major driver genes for non–small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (The Cancer Genome Atlas and COSMIC; r = 0.90–0.99), with the principal differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naïve tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR = 5 × 10−7 for EGFR and ERBB2), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (&gt;18.6% patients).Conclusions: Together, these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. Clin Cancer Res; 24(15); 3528–38. ©2018 AACR.
High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling
Authors: Hayashi Takuji , Fujita Kazutoshi , Nojima Satoshi , Hayashi Yujiro , Nakano Kosuke , Ishizuya Yu , Wang Cong , Yamamoto Yoshiyuki , Kinouchi Toshiro , Matsuzaki Kyosuke , Jingushi Kentaro , Kato Taigo , Kawashima Atsunari , Nagahara Akira , Ujike Takeshi , Uemura Motohide , Pena Maria Del Carmen Rodriguez , Gordetsky Jennifer B. , Morii Eiichi , Tsujikawa Kazutake , Netto George J. , Nonomura Norio 
Published: May 2018

Abstract
Purpose: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation.
Experimental Design: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+;Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed.
Results: HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer.
Conclusions: HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. Clin Cancer Res; 24(17); 4309–18. ©2018 AACR.
Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma
Authors: Bezrookove Vladimir , Nosrati Mehdi , Miller James R. , De Semir David , Dar Altaf A. , Vosoughi Elham , Vaquero Edith , Sucker Antje , Lazar Alexander J. , Gershenwald Jeffrey E. , Davies Michael A. , Schadendorf Dirk , Kashani-Sabet Mohammed 
Published: May 2018

Abstract
Purpose: Previous studies have indicated an important role for pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis. Here we aimed to confirm the role of PHIP copy number in successive stages of melanoma progression.
Experimental Design: PHIP copy number was examined using FISH in three independent cohorts by recording the percentage of cells harboring ≥3 copies of PHIP. The impact of PHIP copy number on survival was assessed using Cox regression analysis. The enrichment of PHIP was assessed in various molecular melanoma subtypes. PHIP expression was analyzed in The Cancer Genome Atlas (TCGA) melanoma cohort.
Results: Elevated PHIP copy number was significantly predictive of reduced distant metastasis-free survival (DMFS) and disease-specific survival (DSS), and increased prevalence of ulceration in primary melanoma (cohort No. 1). By multivariate analysis, PHIP FISH scores were independently predictive of DMFS and DSS. PHIP copy number was enriched in metastatic melanomas harboring mutant NRAS or expressing PTEN protein (cohort No. 2). PHIP copy number was significantly elevated in metastatic melanomas when compared with matched primary tumors from the same patient (cohort No. 3). Several of these associations were replicated using TCGA cohort analysis.
Conclusions: These results underscore the important role of PHIP copy-number elevation in melanoma progression, and identify molecular subtypes of melanoma in which PHIP is enriched. Finally, as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. Clin Cancer Res; 24(17); 4119–25. ©2018 AACR.
Combining Variables for Cancer Risk Estimation: Is the Sum Better than the Parts?
Authors: Friedenreich Christine M. , McTiernan Anne 
Published: May 2018

Abstract
Examining joint exposures of modifiable breast cancer risk factors may provide advantages over individual exposure–disease association analyses. Using the Healthy Lifestyle Index, Arthur and colleagues analyzed the joint impacts of diet, alcohol, smoking, physical activity, and obesity on breast cancer risk, and subtypes, in postmenopausal women enrolled in the Women's Health Initiative. The analysis provides data for population-attributable risk estimations and future prevention trials to target multiple risk factors. The public health messages for the individual risk factors remain unchanged, however, and it is still not clear whether improving one risk factor can counteract the adverse effects of another. Cancer Prev Res; 11(6); 313–6. ©2018 AACR.
See related article by Arthur et al., p. 317
Symptom Burden of Atrial Fibrillation and Its Relation to Interventions and Outcome in Europe
Authors: Schnabel Renate B. , Pecen Ladislav , Rzayeva Nargiz , Lucerna Markus , Purmah Yanish , Ojeda Francisco M. , De Caterina Raffaele , Kirchhof Paulus 
Published: May 2018

Background
Little is known about the association of atrial fibrillation symptom burden with quality of life and outcomes.

Methods and Results

In the Prevention of Thromboembolic Events–European Registry in Atrial Fibrillation (n=6196 patients with atrial fibrillation; mean±SD age, 71.8±10.4 years; 39.7% women), we assessed European Heart Rhythm Association score symptoms and calculated correlations with the standardized health status questionnaire (
EQ
‐5D‐5L). Patients were followed up for atrial fibrillation therapies and outcomes (stroke/transient ischemic attack/arterial thromboembolism, coronary events, heart failure, and major bleeding) over 1 year. Most individuals (92%) experienced symptoms. Correlations with health status and quality of life were modest. In multivariable‐adjusted regression models, the dichotomized European Heart Rhythm Association score (intermediate/frequent versus never/occasional symptoms) was associated with cardioversions (odds ratio [
OR
], 1.21; 95% confidence interval [
CI
], 1.01–1.45) and catheter ablation (
OR,
1.97; 95%
CI,
1.44–2.69), and inversely related with heart rate control (
OR,
0.80; 95%
CI,
0.70–0.92) and heart failure incidence (
OR,
1.65; 95%
CI,
1.16–2.34). Anxiety was inversely related with stroke/transient ischemic attack/arterial thromboembolism (
OR,
0.55; 95%
CI,
0.32–0.93), whereas chest pain related positively with coronary events (
OR,
2.45; 95%
CI,
1.42–4.22). Fatigue (
OR,
1.84; 95%
CI,
1.30–2.60), dyspnea (
OR,
2.33; 95%
CI,
1.63–3.33), and anxiety (
OR,
1.72; 95%
CI,
1.16–2.55) were associated with heart failure incidence. Palpitations were positively associated with cardioversion (
OR,
1.32; 95%
CI,
1.08–1.61) and ablation therapy (
OR,
2.02; 95%
CI,
1.48–2.76).

Conclusions
A higher symptom burden, in particular palpitations, predicted interventions to restore sinus rhythm. The score itself had limited predictive value, but its individual components were related to different and specific clinical events, and may thus be helpful to target patient management.
MR‐proADM as a Prognostic Marker in Patients With ST‐Segment–Elevation Myocardial Infarction—DANAMI‐3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy
Authors: Falkentoft Alexander C. , Rørth Rasmus , Iversen Kasper , Høfsten Dan E. , Kelbæk Henning , Holmvang Lene , Frydland Martin , Schoos Mikkel M. , Helqvist Steffen , Axelsson Anna , Clemmensen Peter , Jørgensen Erik , Saunamäki Kari , Tilsted Hans‐Henrik , Pedersen Frants , Torp‐Pedersen Christian , Kofoed Klaus F. , Goetze Jens P. , Engstrøm Thomas , Køber Lars 
Published: May 2018

Background

Midregional proadrenomedullin (
MR
‐pro
ADM
) has demonstrated prognostic potential after myocardial infarction (
MI
). Yet, the prognostic value of
MR
‐pro
ADM
at admission has not been examined in patients with ST‐segment–elevation
MI
(
STEMI
).

Methods and Results

The aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with
ST
‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of
MR
‐pro
ADM
with short‐ and long‐term mortality and hospital admission for heart failure in patients with
ST
‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of
MR
‐pro
ADM
was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of
MR
‐pro
ADM
was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11;
P
=0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29;
P
<0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32–5.58;
P
=0.007). For 30‐day and 3‐year mortality, the area under the curve for
MR
‐pro
ADM
was 0.77 and 0.78, respectively. For 3‐year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85;
P
=0.02) after addition of
MR
‐pro
ADM
.

Conclusions

Elevation of admission
MR
‐pro
ADM
was associated with long‐term mortality and heart failure, whereas the association with short‐term mortality was borderline significant.
MR
‐pro
ADM
may be a marker of prognosis after ST‐segment–elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models.

Clinical Trial Registration

URL
:
http:/www.ClinicalTrials.gov
/. Unique identifiers:
NCT
01435408 and
NCT
01960933.