bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of “Protective” Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes
Authors: DeVito Elise E , Jensen Kevin P , O’Malley Stephanie S , Gueorguieva Ralitza , Krishnan-Sarin Suchitra , Valentine Gerald , Jatlow Peter I , Sofuoglu Mehmet 
Published: April 2019

Abstract

Introduction
Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products’ reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties. Menthol’s cooling and anesthetic effects may increase appeal by counteracting nicotine’s aversive effects. Genetics provide a method for modeling individual differences in sensitivity to nicotine’s effects. A common polymorphism, rs16969968, encoded in the α5 nicotinic acetylcholine receptor subunit gene (CHRNA5), is a well-recognized marker for smoking risk and reduces sensitivity to nicotine aversiveness.

Methods
This pilot study tested how flavors impacted e-cigarette appeal and self-administration. In a single testing day, cigarette smokers (N = 32; 94% menthol-smokers) self-administered e-cigarettes containing e-liquids differing in nicotine level (0 mg/mL, 24 mg/mL) and flavor (unflavored, menthol, fruit-flavored) within directed and ad libitum e-cigarette paradigms. Subjective drug effects, number of puffs, rs16969968 genotype, plasma nicotine, and menthol glucuronide levels were collected.

Results
Menthol partially ameliorated nicotine aversiveness; fruit did not. In nicotine’s absence, fruit flavor increased self-reported preference and ad libitum use relative to menthol-containing or unflavored e-liquids. Individuals with high-smoking-risk rs16969968 genotype (N = 7) reported greater craving alleviation following directed administration of nicotine-containing e-liquids, showed a trend rating nicotine-containing e-liquids as less harsh, and self-administered more nicotine during ad libitum compared to individuals with low-smoking-risk genotype (N = 23).

Conclusions
While menthol countered aversiveness of nicotine-containing e-liquids, fruit flavor increased appeal of nicotine-free e-liquids. These preliminary findings suggest menthol and fruit flavor increase e-cigarettes’ appeal through distinct mechanisms.

Implications
This study provides a detailed characterization of the effects of flavors (unflavored, menthol, fruit), nicotine (0 mg/mL, 24 mg/mL) and their interactions on the subjective drug effects and ad libitum self-administration of e-cigarettes. Genetics were used to assess these effects in higher-smoking-risk (diminished sensitivity to nicotine aversiveness) and lower-risk groups. Findings could inform impact of regulation of flavors or nicotine in e-cigarettes, and their impacts on vulnerable sub-populations.
The lung in a cohort of rheumatoid arthritis patients—an overview of different types of involvement and treatment
Authors: Duarte Ana C , Porter Joanna C , Leandro Maria J 
Published: April 2019

Abstract

Objectives
Lung involvement in RA has several manifestations and is a major cause of morbidity and mortality. The aim of this study was to characterize the different types of lung disease and response to treatment in a UK cohort of RA patients.

Methods
RA patients who had undergone high resolution CT scans of the lung were identified and scans reviewed. Demographic data, RA features, complementary exams and treatments were recorded for those with radiological evidence of lung involvement. Descriptive analysis was performed, and Mann–Whitney U and χ2 tests were used for comparison between different radiological subtypes.

Results
Lung disease was reported in 87 (7.7%) of 1129 RA patients, usually (97.7%) post-dating articular symptoms. Most patients had positive RF (74/84; 88.1%) and ACPA (72/82; 87.7%). Interstitial lung disease (ILD) was the most common pattern, reported in 45 (51.7%) patients. Drug-induced lung disease was reported in 2 of 64 (3.1%) patients treated with MTX. Rituximab was used in 26 (57.8%) patients with ILD, with evidence of disease improvement or stabilization in patients with non-specific interstitial pneumonia and organizing pneumonia. During lung disease follow-up (6.7 ± 4.1 years), 22 (25.3%) patients were admitted to hospital with respiratory infections, with 14 (63.6%) of them having underlying bronchiectasis. Lung disease-related mortality was estimated at 8%.

Conclusion
ILD was the most prevalent manifestation of lung involvement in RA and was associated with higher mortality. Immunosuppressive drugs used in RA were rarely associated with lung toxicity, and rituximab demonstrated promising results for the treatment of RA-ILD.
DEVELOPMENT OF CALCULATION TOOL FOR RESPIRATORY TRACT DEPOSITION DEPENDING ON AEROSOLS PARTICLE DISTRIBUTION
Authors: Iwaoka Kazuki , Hosoda Masahiro , Tokonami Shinji , Enriquez Eliza B , Palad Lorna Jean H , Kanda Reiko 
Published: April 2019

Abstract
Inhalation exposures occur by inhaled radioactive nuclides depositing in the various locations in the respiratory tract (International Commission on Radiological Protection Publication 66). Respiratory tract deposition depends on particle size. The sensitivity to ionising radiation is different among respiratory regions. Under actual atmospheric environments, the radionuclides attach to aerosols of various size in the atmosphere, so the particle size of radionuclides changes differently. Therefore, it is important for the estimation of health impact to calculate the respiratory tract deposition under atmospheric environment wherein the various sizes of radioactive nuclides (i.e. polydisperse particles) exists. In this study, a tool which can calculate the respiratory tract deposition on the basis of polydisperse particle size distribution was developed to estimate dose depending on variable aerosol particle sizes.
The “Power of Presence”: Professional Women Leaders and Family Law Reform in Morocco
Authors: Charrad Mounira M , Stephan Rita 
Published: April 2019

Abstract
The 2004 reforms of Islamic family law in Morocco brought about a long-awaited expansion of women’s rights. The Moroccan women’s movement was a key player in the promulgation of the reforms. We highlight the role of professional women leaders in the movement and show how they developed political capital and the “power of presence” by combining (i) professional attainment, (ii) leadership in women’s organizations, and (iii) active participation or positions in politics and civil society. We suggest that more needs to be understood about the implications of women’s education and professional attainment for legal change, especially in the Middle East.
Relationship between Hope and Quality of Life in Primary Care Patients: Vitality as a Mechanism
Authors: Lucas Abigael G , Chang Edward C , Morris Lily E , Angoff Harrison D , Chang Olivia D , Duong Ashley H , Li Mingqi , Hirsch Jameson K 
Published: April 2019

AbstractThe present study examined the role of vitality as a mediator of the association between dispositional hope and quality of life (QoL) (namely, physical health, psychological health, social relationships, and environment) in a sample of 101 adult primary care patients. Vitality was found to fully mediate the relationship between hope and physical health, social relationships, and environment. In addition, vitality was found to partially mediate the association between hope and psychological health. The present findings are consistent with a model in which vitality represents an important mechanism through which hope affects QoL in adults. Accordingly, these findings point to the importance of fostering both hope and vitality in efforts to promote positive QoL in adults.
Strengthening the Voice of Those with Mental Health Issues: A Community Approach to Developing a Mental Health Identification System
Authors: Quinn Andrew , Otteson Mary 
Published: April 2019

AbstractThis article describes how an action research approach was used to involve a community of individuals with mental health issues and their support systems in the development and adoption of a mental health identification (ID) card. The intent of the card was to provide individuals with mental health issues a way to communicate and manage the idiosyncratic nature of their behaviors. A credit card–size ID card was developed that has the individual’s picture, address, diagnosis, idiosyncratic behaviors, best approach with the individual when those behaviors are present, medications, allergies, and emergency contact information. Benefits and concerns about the ID system in regard to the cardholder, card recipients, the provision of consent, Health Insurance Portability and Accountability Act compliance, and the balancing of reducing and increasing stigmas and stereotypes emerged throughout the process. In the end, the ID card has come to be seen as a social justice mechanism that allows for communication and awareness for those with mental health issues.
The Relative Importance of Modeling Site Pattern Heterogeneity Versus Partition-Wise Heterotachy in Phylogenomic Inference
Authors: Wang Huai-Chun , Susko Edward , Roger Andrew J 
Published: April 2019

AbstractLarge taxa-rich genome-scale data sets are often necessary for resolving ancient phylogenetic relationships. But accurate phylogenetic inference requires that they are analyzed with realistic models that account for the heterogeneity in substitution patterns amongst the sites, genes and lineages. Two kinds of adjustments are frequently used: models that account for heterogeneity in amino acid frequencies at sites in proteins, and partitioned models that accommodate the heterogeneity in rates (branch lengths) among different proteins in different lineages (protein-wise heterotachy). Although partitioned and site-heterogeneous models are both widely used in isolation, their relative importance to the inference of correct phylogenies has not been carefully evaluated. We conducted several empirical analyses and a large set of simulations to compare the relative performances of partitioned models, site-heterogeneous models, and combined partitioned site heterogeneous models. In general, site-homogeneous models (partitioned or not) performed worse than site heterogeneous, except in simulations with extreme protein-wise heterotachy. Furthermore, simulations using empirically-derived realistic parameter settings showed a marked long-branch attraction (LBA) problem for analyses employing protein-wise partitioning even when the generating model included partitioning. This LBA problem results from a small sample bias compounded over many single protein alignments. In some cases, this problem was ameliorated by clustering similarly-evolving proteins together into larger partitions using the PartitionFinder method. Similar results were obtained under simulations with larger numbers of taxa or heterogeneity in simulating topologies over genes. For an empirical Microsporidia test data set, all but one tested site-heterogeneous models (with or without partitioning) obtain the correct Microsporidia+Fungi grouping, whereas site-homogenous models (with or without partitioning) did not. The single exception was the fully partitioned site-heterogeneous analysis that succumbed to the compounded small sample LBA bias. In general unless protein-wise heterotachy effects are extreme, it is more important to model site-heterogeneity than protein-wise heterotachy in phylogenomic analyses. Complete protein-wise partitioning should be avoided as it can lead to a serious LBA bias. In cases of extreme protein-wise heterotachy, approaches that cluster similarly-evolving proteins together and coupled with site-heterogeneous models work well for phylogenetic estimation.
Metapopulation Vicariance, Age of Island Taxa and Dispersal: A Case Study Using the Pacific Plant Genus Planchonella (Sapotaceae)
Authors: Swenson Ulf , Havran J Christopher , Munzinger Jérôme , Mcloughlin Stephen , Nylinder Stephan 
Published: April 2019

Abstract
Oceanic islands originate from volcanism or tectonic activity without connections to continental landmasses, are colonized by organisms, and eventually vanish due to erosion and subsidence. Colonization of oceanic islands occurs through long-distance dispersals (LDDs) or metapopulation vicariance, the latter resulting in lineages being older than the islands they inhabit. If metapopulation vicariance is valid, island ages cannot be reliably used to provide maximum age constraints for molecular dating. We explore the relationships between the ages of members of a widespread plant genus (Planchonella, Sapotaceae) and their host islands across the Pacific to test various assumptions of dispersal and metapopulation vicariance. We sampled three nuclear DNA markers from 156 accessions representing some 100 Sapotaceae taxa, and analyzed these in BEAST with a relaxed clock to estimate divergence times and with a phylogeographic diffusion model to estimate range expansions over time. The phylogeny was calibrated with a secondary point (the root) and fossils from New Zealand. The dated phylogeny reveals that the ages of Planchonella species are, in most cases, consistent with the ages of the islands they inhabit. Planchonella is inferred to have originated in the Sahul Shelf region, to which it back-dispersed multiple times. Fiji has been an important source for range expansion in the Pacific for the past 23 myr. Our analyses reject metapopulation vicariance in all cases tested, including between oceanic islands, evolution of an endemic Fiji–Vanuatu flora, and westward rollback vicariance between Vanuatu and the Loyalty Islands. Repeated dispersal is the only mechanism able to explain the empirical data. The longest (8900 km) identified dispersal is between Palau in the Pacific and the Seychelles in the Indian Ocean, estimated at 2.2 Ma (0.4–4.8 Ma). The first split in a Hawaiian lineage (P. sandwicensis) matches the age of Necker Island (11.0 Ma), when its ancestor diverged into two species that are distinguished by purple and yellow fruits. Subsequent establishment across the Hawaiian archipelago supports, in part, progression rule colonization. In summary, we found no explanatory power in metapopulation vicariance and conclude that Planchonella has expanded its range across the Pacific by LDD. We contend that this will be seen in many other groups when analyzed in detail.
Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes
Authors: Biserni Martina , Mesnage Robin , Ferro Raquel , Wozniak Eva , Xenakis Theodoros , Mein Charles A , Antoniou Michael N 
Published: April 2019

Abstract
Exposure to endocrine disrupting chemicals is an established risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the potential of glyphosate, 2, 4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE) to induce lipid accumulation in murine 3T3-L1 adipocytes. Only QpE caused a dose-dependent statistically significant triglyceride accumulation from a concentration of 5 up to 100 µM. The QpE commercial formulation Targa Super was 100 times more cytotoxic than QpE alone. Neither the estrogen receptor antagonist ICI 182, 780 nor the glucocorticoid receptor antagonist RU486 was able to block the QpE-induced lipid accumulation. RNAseq analysis of 3T3-L1 adipocytes exposed to QpE suggests that this compound exerts its lipid accumulation effects via a peroxisome proliferator-activated receptor gamma (PPARγ)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPARγ reporter gene assay at 100 µM, reaching 4% of the maximal response produced by rosiglitazone, which acts as a positive control. This indicates that lipid accumulation induced by QpE is only in part caused by PPARγ activation. The lipid accumulation capability of QpE we observe suggest that this pesticide, whose use is likely to increase in coming years may have a hitherto unsuspected obesogenic property.
Blockade of the NLRP3/Caspase-1 Axis Ameliorates Airway Neutrophilic Inflammation in a Toluene Diisocyanate-Induced Murine Asthma Model
Authors: Chen Shuyu , Yao Lihong , Huang Peikai , He Qiaoling , Guan Hongbing , Luo Yiqin , Zou Zehong , Wei Shushan , Peng Guoyou , Yan Jie , Chen Rongchang , Zhang Qingling , Tao Ailin 
Published: April 2019

Abstract
Multiple studies have addressed the vital role of Nod-like receptor protein 3(NLRP3)/caspase-1/IL-1β signaling in asthma. Yet, the role of NLRP3/caspase-1 in toluene diisocyanate (TDI)-induced asthma is still obscure. The aim of this study is to investigate the role of the NLRP3/caspase-1 axis in TDI-induced asthma. Using an established murine model of TDI-induced asthma as described previously, we gave the asthmatic mice a highly selective NLRP3 inhibitor, MCC950, as well as the specific caspase-1 inhibitors VX-765 and Ac-YVAD-CHO for therapeutic purposes. Airway resistance was measured and bronchoalveolar lavage fluid was analyzed. Lungs were examined by histology, immunohistochemistry, Western blotting, and flow cytometry. TDI exposure elevated the expression of NLRP3 and caspase-1 that was coupled with increased airway hyperresponsiveness (AHR), neutrophil-dominated cell infiltration, pronounced goblet cell metaplasia, extensive collagen deposition, and increased TH2/TH17 responses. Both VX-765 and Ac-YVAD-CHO effectively inhibited the activation of caspase-1 in TDI-asthmatic mice that was accompanied by dramatic attenuation of AHR, airway inflammation, and airway remodeling, in addition to a decreased TH2 response and lower levels of IL-18 and IL-1β. MCC950 blocked the activation of NLRP3 and downregulated protein expression of caspase-1, IL-1β, and IL-18 in TDI-exposed mice. Furthermore, MCC950 remarkably alleviated AHR, airway inflammation, airway remodeling, and significantly suppressed TH2/TH17 responses. These findings suggested that blockade of the NLRP3/caspase-1 axis effectively prevents the progression of TDI-induced asthma and could be used as therapeutic targets for asthmatics.
International transferability of macro-level safety performance functions: a case study of the United States and Italy
Authors: Lee Jaeyoung , Abdel-Aty Mohamed , de Blasiis Maria Rosaria , Wang Xuesong , Mattei Ilaria 
Published: April 2019

Abstract
Safety performance functions (SPFs), or crash-prediction models, have played an important role in identifying the factors contributing to crashes, predicting crash counts and identifying hotspots. Since a great deal of time and effort is needed to estimate an SPF, previous studies have sought to determine the transferability of particular SPFs; that is, the extent to which they can be applied to data from other regions. Although many efforts have been made to examine micro-level SPF transferability, few studies have focused on macro-level SPF transferability. There has been little transferability analysis of macro-level SPFs in the international context, especially between western countries. This study therefore evaluates the transferability of SPFs for several states in the USA (Illinois, Florida and Colorado) and for Italy. The SPFs were developed using data from counties in the United States and provincias in Italy, and the results revealed multiple common significant variables between the two countries. Transferability indexes were then calculated between the SPFs. These showed that the Italy SPFs for total crashes and bicycle crashes were transferable to US data after calibration factors were applied, whereas the US SPFs for total and bicycle crashes, with the exception of the Colorado SPF, could not be transferred to the Italian data. On the other hand, none of the pedestrian SPFs developed was transferable to other countries. This paper provides insights into the applicability of macro-level SPFs between the USA and Italy, and shows a good potential for international SPF transferability. Nevertheless, further investigation is needed of SPF transferability between a wider range of countries.
The Population Health Value Framework: Creating Value by Reducing Costs of Care for Patient Subpopulations With Chronic Conditions
Authors: Gupta Reshma , Roh Lily , Lee Connie , Reuben David , Naeim Arash , Wilson James , Skootsky Samuel A. 
Published: April 2019

Problem
With the growth in risk-based and accountable care organization contracts, creating value by redesigning care to reduce costs and improve outcomes and the patient experience has become an urgent priority for health care systems.

Approach
In 2016, UCLA (University of California, Los Angeles) Health implemented a system-wide population health approach to identify patient populations with high expenses and promote proactive, value-based care. The authors created the Patient Health Value framework to guide value creation: (1) identify patient populations with high expenses and reasons for spending, (2) create design teams to understand the patient story, (3) create custom analytics and spending-based risk stratification, and (4) develop care pathways based on spending risk tiers. Primary care patients with three chronic conditions—dementia, chronic kidney disease (CKD), and cancer—were identified as high-cost subpopulations.

Outcomes
For each patient subpopulation, a multispecialty, multidisciplinary design team identified reasons for spending and created care pathways to meet patient needs according to spending risk. Larger, lower-risk cohorts received necessary but less intensive interventions, while smaller, higher-risk cohorts received more intensive interventions. Preliminary analyses showed a 1% monthly decrease in inpatient bed day utilization among dementia patients (incident rate ratio [IRR] 0.99, P < .03) and a 2% monthly decrease in hospitalizations (IRR 0.98, P < .001) among CKD patients.

Next Steps
Use of the Patient Health Value framework is expanding across other high-cost subpopulations with chronic conditions. UCLA Health is using the framework to organize care across specialties, build capacity, and grow a culture for value.