bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation
Authors: Boada Christian , Zinger Assaf , Tsao Christopher , Zhao Picheng , Martinez Jonathan O. , Hartman Kelly , Naoi Tomoyuki , Sukhovershin Roman , Sushnitha Manuela , Molinaro Roberto , Trachtenberg Barry , Cooke John P. , Tasciotti Ennio 
Published: October 2019

Rationale:
Through localized delivery of rapamycin via a biomimetic drug delivery system, it is possible to reduce vascular inflammation and thus the progression of vascular disease.

Objective:
Use biomimetic nanoparticles to deliver rapamycin to the vessel wall to reduce inflammation in an in vivo model of atherosclerosis after a short dosing schedule.

Methods and Results:

Biomimetic nanoparticles (leukosomes) were synthesized using membrane proteins purified from activated J774 macrophages. Rapamycin-loaded nanoparticles were characterized using dynamic light scattering and were found to have a diameter of 108±2.3 nm, a surface charge of −15.4±14.4 mV, and a polydispersity index of 0.11 +/ 0.2. For in vivo studies, ApoE
−/−
mice were fed a high-fat diet for 12 weeks. Mice were injected with either PBS, free rapamycin (5 mg/kg), or rapamycin-loaded leukosomes (Leuko-Rapa; 5 mg/kg) once daily for 7 days. In mice treated with Leuko-Rapa, flow cytometry of disaggregated aortic tissue revealed fewer proliferating macrophages in the aorta (15.6±9.79 %) compared with untreated mice (30.2±13.34 %) and rapamycin alone (26.8±9.87 %). Decreased macrophage proliferation correlated with decreased levels of MCP (monocyte chemoattractant protein)-1 and IL (interleukin)-b1 in mice treated with Leuko-Rapa. Furthermore, Leuko-Rapa–treated mice also displayed significantly decreased MMP (matrix metalloproteinases) activity in the aorta (mean difference 2554±363.9,
P
=9.95122×10
−6
). No significant changes in metabolic or inflammation markers observed in liver metabolic assays. Histological analysis showed improvements in lung morphology, with no alterations in heart, spleen, lung, or liver in Leuko-Rapa–treated mice.

Conclusions:
We showed that our biomimetic nanoparticles showed a decrease in proliferating macrophage population that was accompanied by the reduction of key proinflammatory cytokines and changes in plaque morphology. This proof-of-concept showed that our platform was capable of suppressing macrophage proliferation within the aorta after a short dosing schedule (7 days) and with a favorable toxicity profile. This treatment could be a promising intervention for the acute stabilization of late-stage plaques.
Derivation and Validation of a Nomogram to Predict In‐Hospital Complications in Children with Tetralogy of Fallot Repaired at an Older Age
Authors: Liu Hong , Zheng Si‐qiang , Li Xin‐ya , Zeng Zhi‐hua , Zhong Ji‐sheng , Chen Jun‐quan , Chen Tao , Liu Zhi‐gang , Liu Xiao‐cheng , Shao Yong‐feng 
Published: October 2019

Background
We aimed to develop and validate a prediction model for in‐hospital complications in children with tetralogy of Fallot repaired at an older age.

Methods and Results

A total of 513 pediatric patients from the Tianjin data set formed a derivation cohort, and 158 pediatric patients from the Hefei and Xiamen data sets formed validation cohorts. We applied least absolute shrinkage and selection operator analysis for variable selection and logistic regression coefficients for risk scoring. We classified patients into different risk categorizations by threshold analysis and investigated the association with in‐hospital complications using logistic regression. In‐hospital complications were defined as death, need for extensive pharmacologic support (vasoactive‐inotrope score of ≥20), and need for mechanical circulatory support. We developed a nomogram based on risk classifier and independent baseline variables using a multivariable logistic model. Based on risk scores weighted by 11 preoperative and 4 intraoperative selected variables, we classified patients as low, intermediate, and high risk in the derivation cohort. With reference to the low‐risk group, the intermediate‐ and high‐risk groups conferred significantly higher in‐hospital complication risks (adjusted odds ratio: 2.721 [95% CI, 1.267–5.841],
P
=0.0102; 9.297 [95% CI, 4.601–18.786],
P
<0.0001). A nomogram integrating the
ARIAR
‐Risk classifier (absolute and relative low risk, intermediate risk, and aggressive and refractory high risk) with age and mean blood pressure showed good discrimination and goodness‐of‐fit for derivation (area under the receiver operating characteristic curve: 0.785 [95%
CI
, 0.731–0.839]; Hosmer‐Lemeshow test,
P
=0.544) and external validation (area under the receiver operating characteristic curve: 0.759 [95%
CI
, 0.636–0.881]; Hosmer‐Lemeshow test,
P
=0.508).

Conclusions
A risk‐classifier–oriented nomogram is a reliable prediction model for in‐hospital complications in children with tetralogy of Fallot repaired at an older age, and strengthens risk/benefit–based decision‐making.
The Image of the Future in the Philosophical and Artistic Versions of Russian Cosmism
Authors: Gacheva Anastasia G. 
Published: October 2019

The article is devoted to the peculiarities of the interpretation of the image of the future in the philosophical tradition of Russian cosmism, as well as the echoes of this vision of the future in Russian writers of the xx century. Cosmists consider reality from the point of view of what it should be, respectively, the image of the future is a model of the perfect state of the world and man. The future for them is projective, and this project should be embodied in reality. Key characteristics of the image of the future in Russian cosmism: axiology, alternative, universality, cosmicity, immortalism, unity of personality and community, assuming the completeness of the development and interaction of both. The future for Russian cosmists is connected with the transition from technical progress, increasing the power of man in the world through artificial tools, to organic progress, associated with the improvement of the human body. Artistic projections of the image of the future are given in the literary texts of the cosmists themselves (K.E. Tsiolkovsky’s sci-Fi works, V. N. Muravyev’s philosophical mystery Sofia and Kitovras), as well as in the poetry of V. Bryusov, V. Mayakovsky, V. Khlebnikov, N. Zabolotsky, in the novels of A. Belyaev and I. Efremov.
Cloud-to-Ground Lightning Flash Density and Thunderstorm Day Distributions over the Contiguous United States Derived from NLDN Measurements: 1993–2018
Authors: Koehler Thomas L. 
Published: October 2019

Abstract
This study employs cloud-to-ground (CG) lightning flash data from the U.S. National Lightning Detection Network (NLDN) to examine temporal and spatial distributions of lightning flash and thunderstorm day (TD) occurrences over the contiguous United States from 1993 to 2018. TD distributions are estimated from NLDN CG flashes using 4 thunder audibility approximations: 5 and 10 nautical mile (n mi; 1 n mi = 1.852 km) audibility ranges, and minima of 1 and 2 flashes within the audibility range. The 26-yr period examined is longer than previous studies using NLDN data, and the TD results can be compared directly to climatologies derived from surface weather observations dating back to the late 1890s. Results based on the abundant NLDN data avoid limitations introduced by the coarse horizontal resolution of surface observations inherent in pre-NLDN TD climatologies. Annual mean flash density and annual and monthly mean TD distributions are derived from almost 568 million NLDN CG flashes. A mean annual maximum of more than 16 flashes km−2 is found near Tampa, Florida. The mean annual TD maximum of 113 days (from at least 2 flashes within 10 n mi) occurs in southern Florida. Regions exceeding 70 TDs are found from eastern Texas eastward into Florida, and over the southern Rocky Mountains. Large positive deviations from the mean number of TDs extend from Texas northwestward into Colorado during 2003–07, followed by large negative deviations over the same region during 2008–12. Both deviation patterns are similar to expected summertime precipitation anomaly patterns over the United States during El Niño and La Niña years, respectively.
An analysis of the design factors of work procedures: implications for local government administration in South Africa
Authors: Nzewi Ogochukwu Iruoma , Yan Bingwen , Olutuase Sam 
Published: October 2019

Work design and, in particular, work procedures have been a focus of much research in organisational development studies. However, their relevance and practice are rarely researched in public administration. This article presents an analysis of important design factors to be considered in the development of work procedures. The relevance of this study in the context of a developmental local government in South Africa is critical at a time when many municipalities are grappling with institutionalising service delivery administrative processes for the effective delivery of basic services. A quantitative research approach using a cross-sectional survey design involved 250 employees from three municipalities in South Africa. Structural equation modelling was used to determine the impact of critical factors on the design of work procedures for local municipalities. The study finds that out of the eight critical factors tested, the participation of local government employees in the development of work procedures and an effective municipal communication apparatus are significantly associated with the design of work procedures. We conclude that the design of work procedures should entail employee participation engendered through communication that freely and openly allows all stakeholders to share a common vision for service delivery. The findings further provide a theoretically underpinned framework as regards setting policy for achieving effective work procedures in similar local government contexts across the developing world. Points for practitioners While leadership and accountability, continuous improvement, shared vision, effective communication, and organisational policy are important factors to consider, employee participation is the most critical factor that affects the design and utilisation of work procedures in local municipalities. Policymakers/practitioners must seek empirical evidence as a basis for determining design considerations for effective work procedure design and redesign. This article provides a theoretically underpinned framework as regards setting policy for achieving effective work procedures in local municipalities.
Mini-midline in difficult intravenous access patients in emergency department: A prospective analysis
Authors: Gilardi Emanuele , Giannuzzi Rosangela , WoldeSellasie Kidane , Piano Alfonso , Pittiruti Mauro , Scoppettuolo Giancarlo 
Published: October 2019

Background: “Difficult intravenous access” patients represent a challenge within an emergency department as they often require many attempts to insert a peripheral short cannula in the emergency room or during the whole hospitalization. This can lead to many problems in terms of patient discomfort, increase of cost, and prolonged treatment time. Objectives: This study aimed to reduce the number of attempts needed for a short-cannula insertion or preventing insertion of a central vascular access by placing an ultrasound-guided long cannula during the emergency department visit. Material and methods: The insertion of mini-midline was monitored within an emergency room in 50 patients considered difficult intravenous access patients, who failed two attempts at peripheral venous access insertion and/or required the use of an alternative vascular device. Results: A total of 46 patients out of 50 were monitored. In 38 (82%) patients, the device was removed due to the end of the indication, and in six of them, it was replaced by a central venous catheter. Two devices were left inside even after discharge and were then removed at the end of indication. In eight (17%) patients, the device was removed due to accidental removal (4) and malfunction (4). In all the cases, the average duration of the insertion procedure was 10 min. The mean dwell time accounted to 7 and 9 days. Conclusion: The insertion of a mini-midline as part of the first emergency room visit in selected patients is a rapid, safe, and cost-effective procedure, which can provide the patient with stable venous access during the all hospitalization time.
Closed testing of each group versus the others combined in a multiple group analysis
Authors: Lachin John M , Bebu Ionut 
Published: October 2019

Background: Many studies, such as a study of comparative effectiveness, entail a comparison of the beneficial and adverse effects of multiple K[Formula: see text] 2 competing therapies. Often, the analysis consists of a comparison of the K groups using an omnibus ( T2-like) test for any difference among the groups followed by pairwise comparisons with adjustments for multiple tests. Methods: We evaluate the properties of an analysis strategy in which each group is compared to the average of the others in hopes of establishing the overall superiority (or harm) of at least one of the therapies. Testing of one-versus-others can be accomplished for virtually any model using simple tests, and the type I error probability [Formula: see text] can be controlled by conducting such tests under the closed testing principle. Testing using linear models, the family of generalized linear models, and Cox proportional hazards models is described with examples. Results: Since each tested hypothesis compares one treatment to the average of the others, the K-level null hypothesis in the tree of closed testing is equivalent to any of the ( K−1)-level tests, thus reducing the number of tests required. This applies to linear, generalized linear, and Cox proportional hazards models. While the Bonferroni, Holm, and Hommel procedures preserve the desired level [Formula: see text], all are conservative relative to closed one-versus-others testing and closed testing in general provides greater power. Conclusion: Testing each of the multiple treatments versus the average of the others is readily and efficiently conducted under the closed testing principle and may be especially useful in the assessment of studies of comparative effectiveness.
Peer Mentoring in the Do-it-Yourself Artificial Pancreas System Community
Authors: Crocket Hamish 
Published: October 2019

Background: The do-it-yourself (DIY) artificial pancreas system (APS) community is led by people with diabetes (PWD) and their families. In contrast to standard models of care, in which health care professionals are responsible for the education and training of PWD and their families, within the DIY APS, community users are reliant on their peers for education and training. The provision of this support has not previously been studied. This article focuses on the role of mentors within the DIY APS community. Method: Semistructured interviews were conducted with mentors ( n = 9) who were identified with assistance from the DIY APS community. Thematic analysis was undertaken. Results were presented to select participants who endorsed the results as an accurate description of mentoring in the DIY APS community. Results: Mentors’ primary motivation was altruism. An empathetic, process-focused approach was modeled by prominent mentors. The use of online forums as the primary source of user support was perceived to be an effective method for sharing the workload. Key challenges for mentors included the frequency with which users asked questions that were answered in the existing documentation, dealing with conflict and managing workload. Most participants did not perceive mentoring to be risky, but did take steps to ensure that users were taking responsibility for their own systems. Conclusion: This study is the first to examine the role of mentors within the DIY APS community and also within the broader diabetes online community. Future research might seek to quantify the empathetic, process-focused approach to mentoring.
Assessing an ASCO Decision Aid for Improving the Accuracy and Attribution of Serious Adverse Event Reporting From Investigators to Sponsors
Authors: Mileham Kathryn F. , Schenkel Caroline , Chuk Meredith K. , Buchmeier Andrea , Perez Raymond P. , Hurley Patricia , Levit Laura A. , Garrett-Mayer Elizabeth , Davis Courtney , Bruinooge Suanna S. , Vose Julie 
Published: October 2019

PURPOSE: Investigators often send reports to sponsors that incorrectly categorize adverse event (AE)s as serious or attribute AEs to investigational drugs. Such errors can contribute to high volumes of uninformative investigational new drug safety reports that sponsors submit to the US Food and Drug Administration and participating investigators, which strain resources and impede the detection of valid safety signals. To improve the quality of serious AE (SAE) reporting by physician-investigators and research staff, ASCO developed and tested a Decision Aid. METHODS: A preliminary study with crossover design was conducted in a convenience sample. Physician-investigators and research staff were randomly assigned to receive case studies. Case studies were assessed for seriousness and attribution, first unassisted and then with the Decision Aid. Participants completed a feedback survey about the Decision Aid. Effectiveness of reporting and attribution are reported as odds ratios (ORs) with 95% CI. Power to detect associations was limited because of a small sample size. RESULTS: The Decision Aid did not significantly affect accuracy of determining seriousness (OR, 0.87; 95% CI, 0.31 to 2.46), but it did significantly increase accuracy of attributing an SAE to a drug (OR, 3.60; 95% CI, 1.15 to 11.4). Most of the 29 participants reported that the Decision Aid was helpful (93%) and improved decision-making time (69%) and confidence in reporting (83%), and that they would use the Decision Aid in practice (83%). CONCLUSION: The Decision Aid shows promise as a method to improve the quality of SAE attribution, which may improve the detection of valid safety signals and reduce the administrative burden of uninformative investigational new drug safety reports. Study of the Decision Aid in a larger sample with analysis stratified by participant role and SAE reporting experience would further assess the tool’s impact.
Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae
Authors: Hollenstein David M. , Gómez-Sánchez Rubén , Ciftci Akif , Kriegenburg Franziska , Mari Muriel , Torggler Raffaela , Licheva Mariya , Reggiori Fulvio , Kraft Claudine 
Published: October 2019

ABSTRACT
Autophagy is initiated by the formation of a phagophore assembly site (PAS), the precursor of autophagosomes. In mammals, autophagosome formation sites form throughout the cytosol in specialized subdomains of the endoplasmic reticulum (ER). In yeast, the PAS is also generated close to the ER, but always in the vicinity of the vacuole. How the PAS is anchored to the vacuole and the functional significance of this localization are unknown. Here, we investigated the role of the PAS–vacuole connection for bulk autophagy in the yeast Saccharomyces cerevisiae. We show that Vac8 constitutes a vacuolar tether that stably anchors the PAS to the vacuole throughout autophagosome biogenesis via the PAS component Atg13. S. cerevisiae lacking Vac8 show inefficient autophagosome–vacuole fusion, and form fewer and smaller autophagosomes that often localize away from the vacuole. Thus, the stable PAS–vacuole connection established by Vac8 creates a confined space for autophagosome biogenesis between the ER and the vacuole, and allows spatial coordination of autophagosome formation and autophagosome–vacuole fusion. These findings reveal that the spatial regulation of autophagosome formation at the vacuole is required for efficient bulk autophagy.
A homeostatic mechanism rapidly corrects aberrant nucleocytoplasmic ratios maintaining nuclear size in fission yeast
Authors: Cantwell Helena , Nurse Paul 
Published: October 2019

ABSTRACT
Nuclear size scales with cell size across a wide range of cell types. The mechanism by which this scaling is maintained in growing cells remains unclear. Here, we investigate the mechanism of nuclear size homeostasis in the simple eukaryote fission yeast, by monitoring the recovery of aberrant nuclear volume to cell volume (N/C) ratios following perturbation. We demonstrate that both high and low N/C ratios correct rapidly, maintaining nuclear size homeostasis. We assess the kinetics of nuclear and cellular growth and of N/C ratio correction, and demonstrate that nuclear and cellular growth rates are not directly coupled. We propose that the mechanism underlying nuclear size homeostasis involves multiple limiting factors implicated in processes including nucleocytoplasmic transport, lipid biogenesis and RNA processing. We speculate that these link cellular size increases to changes in nuclear contents, which in turn lead to changes in nuclear membrane surface area. Our study reveals that there is rapid nuclear size homeostasis in cells, informing understanding of nuclear size control and size homeostasis of other membrane-bound organelles.
Information vs. Automation and Implications for Dynamic Pricing
Authors: Bollinger Bryan K. , Hartmann Wesley R. 
Published: October 2019

Essential resources, like electricity and water, can experience rapidly changing demand or supply while the other side of the market is unchanged. Short-run price variation could efficiently allocate resources at these critical times but only if consumers exhibit short-run demand elasticity. The question for firms in these markets has always been how to enable this response. Randomized control trials are increasingly used to test dynamic pricing and technologies that can assist in response by providing information and/or automated response. However, the trials typically do not randomize short-run prices. This paper illustrates how demand from a randomly assigned control group can be used to test the effectiveness of different technologies in increasing short-term price elasticity. To do so, we use a nonparametric control function approach that eliminates the bias inherent in estimating short-term price response using only household random assignment. We find that only automation technology leads to the short-term price elasticity needed to justify real-time pricing. This paper was accepted by Matthew Shum, marketing.
How Do Gender Quotas Affect Workplace Relationships? Complementary Evidence from a Representative Survey and Labor Market Experiments
Authors: Ip Edwin , Leibbrandt Andreas , Vecci Joseph 
Published: October 2019

Gender quotas are frequently proposed to address persistent gender imbalances in managerial roles. However, it is unclear how quotas for female managers affect organizations and whether quotas improve or damage relationships between managers and their subordinates. We conduct a representative survey to study opinions on quotas for female managers and, based upon the survey, design a novel set of experiments to investigate how quotas influence wage setting and effort provision. Our findings reveal that both opinions about gender quotas and workplace behavior crucially depend on the workplace environment. In our survey, we observe that approval for gender quotas is low if women are not disadvantaged in the manager-selection process, regardless of whether there are gender differences in performance. Complementing this evidence, we observe in our experiments that quotas lead to lower effort levels and lower wages in such environments. By contrast, in environments in which women are disadvantaged in the selection process, we observe a higher approval of quotas as well as higher effort levels and higher wages. These findings are consistent with the concept of meritocracy and suggest that it is important to evaluate the perception of gender disadvantages in the workplace environment before implementing quotas. This paper was accepted by Axel Ockenfels, decision analysis.