bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precommitting to choose wisely about low-value services: a stepped wedge cluster randomised trial
Authors: Kullgren Jeffrey Todd , Krupka Erin , Schachter Abigail , Linden Ariel , Miller Jacquelyn , Acharya Yubraj , Alford James , Duffy Richard , Adler-Milstein Julia 
Published: September 2018

BackgroundLittle is known about how to discourage clinicians from ordering low-value services. Our objective was to test whether clinicians committing their future selves (ie, precommitting) to follow Choosing Wisely recommendations with decision supports could decrease potentially low-value orders.MethodsWe conducted a 12-month stepped wedge cluster randomised trial among 45 primary care physicians and advanced practice providers in six adult primary care clinics of a US community group practice.Clinicians were invited to precommit to Choosing Wisely recommendations against imaging for uncomplicated low back pain, imaging for uncomplicated headaches and unnecessary antibiotics for acute sinusitis. Clinicians who precommitted received 1–6 months of point-of-care precommitment reminders as well as patient education handouts and weekly emails with resources to support communication about low-value services.The primary outcome was the difference between control and intervention period percentages of visits with potentially low-value orders. Secondary outcomes were differences between control and intervention period percentages of visits with possible alternate orders, and differences between control and 3-month postintervention follow-up period percentages of visits with potentially low-value orders.ResultsThe intervention was not associated with a change in the percentage of visits with potentially low-value orders overall, for headaches or for acute sinusitis, but was associated with a 1.7% overall increase in alternate orders (p=0.01). For low back pain, the intervention was associated with a 1.2% decrease in the percentage of visits with potentially low-value orders (p=0.001) and a 1.9% increase in the percentage of visits with alternate orders (p=0.007). No changes were sustained in follow-up.ConclusionClinician precommitment to follow Choosing Wisely recommendations was associated with a small, unsustained decrease in potentially low-value orders for only one of three targeted conditions and may have increased alternate orders.Trial registration numberNCT02247050; Pre-results.
The spectra of a new join of graphs
Authors: Paul Somnath 
Published: September 2018

Let [Formula: see text] and [Formula: see text] be three graphs on disjoint sets of vertices and [Formula: see text] has [Formula: see text] edges. Let [Formula: see text] be the graph obtained from [Formula: see text] and [Formula: see text] in the following way: (1) Delete all the edges of [Formula: see text] and consider [Formula: see text] disjoint copies of [Formula: see text]. (2) Join each vertex of the [Formula: see text]th copy of [Formula: see text] to the end vertices of the [Formula: see text]th edge of [Formula: see text]. Let [Formula: see text] be the graph obtained from [Formula: see text] by joining each vertex of [Formula: see text] with each vertex of [Formula: see text] In this paper, we determine the adjacency (respectively, Laplacian, signless Laplacian) spectrum of [Formula: see text] in terms of those of [Formula: see text] and [Formula: see text] As an application, we construct infinite pairs of cospectral graphs.
Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation
Authors: Wang Lanju , Wang Yaohui , Wang Zhenfeng , Qi Yu , Zong Beibei , Liu Meichen , Li Xuefang , Zhang Xingkun , Liu Chengguo , Cao Run , Ma Yuanfang 
Published: September 2018

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1β secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1β secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC.NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1β secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.
Effects of modest iron loading on iron indices in healthy individuals
Authors: Bart Nicole K. , Hungerford Sara L. , Curtis M. Kate , Cheng Hung-Yuan , Southern Jennifer L. , Petousi Nayia , Dorrington Keith L. , Robbins Peter A. 
Published: September 2018

Intravenous iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron. However, in certain chronic disease states such as heart failure, it may be beneficial to administer intravenous iron to individuals who are not strictly iron deficient. The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with intravenous iron in healthy, iron-replete participants. This was a double-blind, controlled study involving 18 male participants. Participants were block-randomized 2:1 to the iron and saline (control) groups. Participants in the iron group received 3.75 mg/kg body wt up to a maximum of 250 mg of intravenous iron, once a month for 6 mo, provided that their ferritin remained measured <300 µg/l within the week before a dose was due and their transferrin saturation remained <45%. Otherwise they received a saline infusion, as did the control participants. Iron indices were measured monthly during the study. The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before, at 3 mo (hemoglobin mass only), and at 6 mo as variables that may be affected by iron loading. Serum ferritin was robustly elevated by intravenous iron by 0.21 µg·l−1·mg−1of iron delivered (95% confidence interval: 0.15–0.26 µg·l−1·mg−1), but the effects on all other iron indices did not reach statistical significance. The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at 6 mo, but the hemoglobin mass was unaffected. We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals.NEW & NOTEWORTHY There has been an increasing interest in administering intravenous iron to patients to alter their iron status. Here, we explore various indices of iron loading and show that in healthy volunteers serum ferritin provides a robust indicator of the amount of iron loaded, with a value of 21 µg/l increase in ferritin per 100 mg of iron loaded.
Charting the human respiratory tract with airborne nanoparticles: evaluation of the Airspace Dimension Assessment technique
Authors: Jakobsson Jonas , Wollmer Per , Löndahl Jakob 
Published: September 2018

Airspace Dimension Assessment (AiDA) is a technique to assess lung morphology by measuring lung deposition of inhaled nanoparticles. Nanoparticles deposit in the lungs predominately by diffusion, and average diffusion distances, corresponding to effective airspace radii ( rAiDA), can be inferred from measurements of particle recovery after varied breath holds. Also, particle recovery after a 0-s breath hold ( R0) may hold information about the small conducting airways. This study investigates rAiDAat different volumetric sample depths in the lungs of healthy subjects. Measurements were performed with 50-nm polystyrene nanospheres on 19 healthy subjects aged 17–67 yr. Volumetric sample depths ranged from 200 to 5,000 ml and breath-hold times from 5 to 20 s. At the examined volumetric sample depths, rAiDAvalues ranged from ~200–600 μm, which correspond to dimensions of the bronchiolar and the gas-exchanging regions of the lungs. R0decreased with volumetric sample depth and showed more intersubject variation than rAiDA. Correlations were found between the AiDA parameters, anthropometry, and lung function tests, but not between rAiDAand R0. For repeated measurements on 3 subjects over an 18-mo period, rAiDAvaried on average within ± 7 μm (± 2.4%). The results indicate that AiDA has potential as an efficient new in vivo technique to assess individual lung properties. The information obtained by such measurements may be of value for lung diagnostics, especially for the distal lungs, which are challenging to examine directly by other means.NEW & NOTEWORTHY This is the first study to measure effective airspace radii ( rAiDA) at volumetric sample depths 200–5,000 ml in healthy subjects by Airspace Dimension Assessment (AiDA). Observed rAiDAwere 200–600 μm, which corresponds to airspaces for the bronchiolar and the gas-exchanging regions around airway generation 14–17. rAiDAcorrelated with lung function tests and anthropometry. Measurements of rAiDAon 3 subjects over 11–18 mo were within ± 7 μm.
Benefits, Harms, and Cost-Effectiveness of Potential Age Extensions to the National Bowel Cancer Screening Program in Australia
Authors: Lew Jie-Bin , St John D. James B. , Macrae Finlay A. , Emery Jon D. , Ee Hooi C. , Jenkins Mark A. , He Emily , Grogan Paul , Caruana Michael , Greuter Marjolein J.E. , Coupé Veerle M.H. , Canfell Karen 
Published: September 2018

Abstract

Background:
The Australian National Bowel Cancer Screening Program (NBCSP) is rolling out 2-yearly immunochemical fecal occult blood test screening in people aged 50 to 74 years. This study aimed to evaluate the benefits, harms, and cost-effectiveness of extending the NBCSP to younger and/or older ages.

Methods:
A comprehensive validated microsimulation model, Policy1-Bowel, was used to simulate the fully rolled-out NBCSP and alternative strategies assuming screening starts at 40 or 45 years and/or ceases at 79 or 84 years given three scenarios: (i) perfect adherence (100%), (ii) high adherence (60%), and (ii) low adherence (40%, as currently achieved).

Results:
The current NBCSP will reduce colorectal cancer incidence (mortality) by 23% to 51% (36% to 74%) compared with no screening (range reflects participation); extending screening to younger or older ages would result in additional reductions of 2 to 6 (2 to 9) or 1 to 3 (3 to 7) percentage points, respectively. With an indicative willingness-to-pay threshold of A$50,000/life-year saved (LYS), only screening from 50 to 74 years [incremental cost-effective ratio (ICER): A$2,984–5,981/LYS) or from 45 to 74 years (ICER: A$17,053–29,512/LYS) remained cost-effective in all participation scenarios. The number-needed-to-colonoscope to prevent a death over the lifetime of a cohort in the current NBCSP is 35 to 49. Starting screening at 45 years would increase colonoscopy demand for program-related colonoscopies by 3% to 14% and be associated with 55 to 170 additional colonoscopies per additional death prevented.

Conclusions:
Starting screening at 45 years could be cost-effective, but it would increase colonoscopy demand and would be associated with a less favorable incremental benefits-to-harms trade-off than screening from 50 to 74 years.

Impact:
The study underpins recently updated Australian colorectal cancer management guidelines that recommend that the NBCSP continues to offer bowel screening from 50 to 74 years.
Interleukin-24 (IL24) Is Suppressed by PAX3-FOXO1 and Is a Novel Therapy for Rhabdomyosarcoma
Authors: Lacey Alexandra , Hedrick Erik , Cheng Yating , Mohankumar Kumaravel , Warren Melanie , Safe Stephen 
Published: September 2018

Abstract
Alveolar rhabdomyosarcoma (ARMS) patients have a poor prognosis, and this is primarily due to overexpression of the oncogenic fusion protein PAX3-FOXO1. Results of RNA-sequencing studies show that PAX3-FOXO1 represses expression of interleukin-24 (IL24), and these two genes are inversely expressed in patient tumors. PAX3-FOXO1 also regulates histone deacetylase 5 (HDAC5) in ARMS cells, and results of RNA interference studies confirmed that PAX3-FOXO1–mediated repression of IL24 is HDAC5-dependent. Knockdown of PAX3-FOXO1 decreases ARMS cell proliferation, survival, and migration, and we also observed similar responses in cells after overexpression of IL24, consistent with results reported for this tumor suppressor–like cytokine in other solid tumors. We also observed in double knockdown studies that the inhibition of ARMS cell proliferation, survival, and migration after knockdown of PAX3-FOXO1 was significantly (&gt;75%) reversed by knockdown of IL24. Adenoviral-expressed IL24 was directly injected into ARMS tumors in athymic nude mice, and this resulted in decreased tumor growth and weight. Because adenoviral IL24 has already successfully undergone phase I in clinical trials, this represents an alternative approach (alone and/or combination) for treating ARMS patients who currently undergo cytotoxic drug therapies.
Current ‘Light’ and ‘Heavy’ Options for Benefit-sharing in the Context of the United Nations Convention on the Law of the Sea
Authors: Voigt-Hanssen Gaute 
Published: September 2018

Abstract
An international legally binding instrument under the United Nations Convention on the Law of the Sea (LOSC) will need to address “Marine Genetic Resources (MGRs), including questions on the sharing of benefits” from areas outside national jurisdiction (ABNJ). Existing international models of benefit-sharing have all evolved in the context of national jurisdiction and cannot readily be put to use in ABNJ. Current use of MGRs from ABNJ is practically non-existent, although any instrument or model would have to both cater for this situation and provide for any potential technological development and increase in use. The aim of this paper is to provide a simplified overview of options for access and benefit-sharing, drawing on existing models from international and national instruments. Existing options could be analysed through separating access from benefit-sharing and assessing them factually in terms of how ‘light’ and ‘heavy’ they are.
Negotiated Health Diplomacy: A Case Study of the EU and Central Asia
Authors: Collins Neil , Bekenova Kristina , Kagarmanova Ainur 
Published: September 2018

Summary
In the soft-power context, health is increasingly seen as an area that generates particular diplomatic benefits, because it is ostensibly non-political and can bring both immediate and long-term advantages to the donor and the recipient country equally. The endeavours of individual member states of the European Union (EU) and the input of the EU itself in Central Asia are examined to see the extent to which the initiatives in health-related areas form part of a wider diplomatic strategy and whether their effectiveness is related to the means by which the planned improved health outcomes are achieved. This article seeks to draw lessons from the European experience to increase understanding of the role of health in global diplomacy.
Does Reinke’s Edema Grade Determine Premalignant Potential?
Authors: Tavaluc Raluca , Herman Howard , Lin Juan , Tan Melin 
Published: September 2018

Objective: Reinke’s edema (RE) is a benign disease of the vocal folds with a wide spectrum of clinical severity. We aim to evaluate the clinical impact of RE grade and determine if RE grade correlates with severity of dysplasia and tobacco exposure. Methods: Patients with isolated RE who underwent surgical excision between December 2010 and December 2014 were retrospectively reviewed. The RE grade was determined from archived laryngeal videostroboscopy exams. Pathologic severity of dysplasia, categorized by squamous intraepithelial neoplasia (SIN) classification, and tobacco history were extracted from medical records. Results: Of 95 lesions, 3 (3.16%) were RE grade 1, 33 (34.74%) were RE grade 2, 24 (25.26%) were RE grade 3, and 35 (36.84%) were RE grade 4. Fifty-nine lesions (62.11%) had no dysplasia (SIN0), 19 (20.00%) had mild dysplasia (SIN1), 15 (15.79%) had moderate dysplasia (SIN 2), and 2 (2.11%) had severe dysplasia (SIN3). The 2 patients with severe dysplasia had grade 4 lesions. No statistical correlation was identified between RE grade and the severity of dysplasia. Furthermore, no statistical correlation was seen between tobacco exposure and the severity of dysplasia or the RE grade. Conclusions: Size of RE lesion does not reflect premalignancy. The majority of RE lesions, regardless of size, have little to no premalignant potential. Severe dysplasia/carcinoma in situ may be more likely seen in grade 4 lesions; however, the paucity of severe dysplasia published in RE data and in this cohort preclude any formal inference. Further study of grade 4 lesions is warranted.
Pneumonia-Associated Hospitalizations, New York City, 2001-2014
Authors: Gu Christopher H. , Lucero David E. , Huang Chaorui C. , Daskalakis Demetre , Varma Jay K. , Vora Neil M. 
Published: September 2018

Objectives: Death certificate data indicate that the age-adjusted death rate for pneumonia and influenza is higher in New York City than in the United States. Most pneumonia and influenza deaths are attributed to pneumonia rather than influenza. Because most pneumonia deaths occur in hospitals, we analyzed hospital discharge data to provide insight into the burden of pneumonia in New York City. Methods: We analyzed data for New York City residents discharged from New York State hospitals with a principal diagnosis of pneumonia, or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis, during 2001-2014. We calculated mean annual age-adjusted pneumonia-associated hospitalization rates per 100 000 population and 95% confidence intervals (CIs). We examined data on pneumonia-associated hospitalizations by sociodemographic characteristics and colisted conditions. Results: During 2001-2014, a total of 495 225 patients residing in New York City were hospitalized for pneumonia, corresponding to a mean annual age-adjusted pneumonia-associated hospitalization rate of 433.8 per 100 000 population (95% CI, 429.3-438.3). The proportion of pneumonia-associated hospitalizations with in-hospital death was 12.0%. The mean annual age-adjusted pneumonia-associated hospitalization rate per 100 000 population increased as area-based poverty level increased, whereas the percentage of pneumonia-associated hospitalizations with in-hospital deaths decreased with increasing area-based poverty level. The proportion of pneumonia-associated hospitalizations that colisted an immunocompromising condition increased from 18.7% in 2001 to 33.1% in 2014. Conclusion: Sociodemographic factors and immune status appear to play a role in the epidemiology of pneumonia-associated hospitalizations in New York City. Further study of pneumonia-associated hospitalizations in at-risk populations may lead to targeted interventions.
Feasibility study using iodine quantification on dual-energy CT enterography to distinguish normal small bowel from active inflammatory Crohn’s disease
Authors: De Kock Isabelle , Delrue Louke , Lecluyse Clarisse , Hindryckx Pieter , De Vos Martine , Villeirs Geert 
Published: September 2018

Background Assessment of Crohn’s disease (CD) activity is important to identify patients with active inflammation for therapy management. Quantitative analysis can provide objective measurement of disease presence. Purpose To evaluate the feasibility of quantitative analysis of contrast-enhanced dual-energy computed tomography (DECT) data in detection of small bowel inflammation in patients with CD with an emphasis on iodine quantification. Material and Methods DECT enterography was prospectively performed in 20 patients with active CD and in 20 healthy individuals, as the control group. Iodine overlay images were created. Wall thickness, attenuation, absolute iodine density, relative iodine density, and fat fraction were measured in the terminal ileum of all patients by two radiologists. Intraclass correlation coefficients were calculated to assess inter-rater agreement. Parameters were compared between patient groups using mixed model analysis. Receiver operating characteristic (ROC) analysis was performed. Results Both absolute and relative iodine density were significantly higher in active disease than in normal small bowel (all P < 0.001). In contrast, measurement of fat fraction was not significantly different in affected terminal ileal loops compared to normal terminal ileum ( P = 0.075). ROC analysis demonstrated a similar excellent diagnostic accuracy of wall thickness, attenuation, and absolute and relative iodine density with area under the ROC curve (AUC) values in the range of 0.96 for attenuation to 1 for relative iodine density. Conclusion DECT with iodine quantification can be used in distinguishing normal small bowel from active inflammatory CD. Further research should investigate the value of iodine quantification in grading CD activity and in monitoring therapeutic response.
Arterial blood gas changes during cardiac arrest and cardiopulmonary resuscitation combined with passive oxygenation/ventilation: a METI HPS study
Authors: Strnad Matej , Lešnik Damjan , Križmarić Miljenko 
Published: September 2018

Objective High-fidelity simulators can simulate physiological responses to medical interventions. The dynamics of the partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygen pulse saturation (SpO2) during simulated cardiopulmonary resuscitation (CPR) were observed and compared with the results from the literature. Methods Three periods of cardiac arrest were simulated using the METI Human Patient Simulator™ (Medical Education Technologies, Inc., Sarasota, FL, USA): cardiac arrest, chest compression-only CPR, and chest compression-only CPR with continuous flow insufflation of oxygen (CFIO). Results In the first period, the observed values remained constant. In the second period, PaCO2 started to rise and peaked at 63.5 mmHg. In the CFIO period, PaCO2 slightly fell. PaO2 and SpO2 declined only in the second period, reaching their lowest values of 44 mmHg and 70%, respectively. In the CFIO period, PaO2 began to rise and peaked at 614 mmHg. SpO2 exceeded 94% after 2 minutes of CFIO. Conclusions The METI Human Patient Simulator™ accurately simulated the dynamics of changes in PaCO2. Use of this METI oxygenation model has some limitations because the simulated levels of PaO2 and SpO2 during cardiac arrest correlate poorly with the results from published studies.