bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive role of PPARγ in the IgE-dependent activation of mast cells
Authors: Nagata Kazuki , Kasakura Kazumi , Miura Ryosuke , Yashiro Takuya , Nishiyama Chiharu 
Published: October 2019

Abstract
Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγ is a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγ is expressed in activated MCs, the effect of PPARγ suppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγ knockdown on the function of IgE plus antigen (Ag)-stimulated MCs using siRNA-transfected bone marrow-derived MCs (BMMCs). We found that the mRNA expression level of cytokines in IgE/Ag-stimulated BMMCs was significantly increased in PPARγ knockdown BMMCs, and IgE/Ag-mediated degranulation and the protein production level of TNF-α was moderately increased by PPARγ knockdown, whereas the cell surface expression level of FcεRI was not affected by PPARγ knockdown. Oral administration of pioglitazone (PPARγ agonist) significantly suppressed body temperature change of mice in passive systemic anaphylaxis, supporting the inhibitory functions of PPARγ in IgE/Ag-dependent activation of MCs in vivo. IgE-mediated up-regulation of mRNA levels of Ptgs2 (encoding COX-2) was drastically enhanced in PPARγ knockdown BMMCs. Although several prostaglandin (PG) derivatives are known to be ligands for PPARγ, treatment with a COX inhibitor, acetyl salicylic acid, up-regulated the IgE-mediated increase of Il13, Tnf and Ptgs2 mRNA levels in a synergistic manner with PPARγ siRNA. Knockdown of COX-1 and/or COX-2 by siRNA showed that suppression of IgE/Ag-mediated activation was mainly dependent on COX-1. Taken together, these results indicate that PPARγ suppresses IgE/Ag-induced transactivation of cytokine genes and the Ptgs2 gene in MCs in a manner distinguishable from that of PGs.
The effect of food on the pharmacokinetics of oral ivermectin
Authors: Duthaler Urs , Leisegang Rory , Karlsson Mats O , Krähenbühl Stephan , Hammann Felix 
Published: October 2019

Abstract

Background
Ivermectin is an older anthelminthic agent that is being studied more intensely given its potential for mass drug administration against scabies, malaria and other neglected tropical diseases. Its pharmacokinetics (PK) remain poorly characterized. Furthermore, the majority of PK trials are performed under fasted-state dosing conditions, and the effect of food is therefore not well known. To better plan and design field trials with ivermectin, a model that can account for both conditions would be valuable.

Objectives
To develop a PK model and characterize the food effect with single oral doses of ivermectin.

Patients and methods
We performed a population-based PK analysis of data pooled from two previous trials of a single dose of 12 mg ivermectin, one with dosing after a high-fat breakfast (n=12) and one with fasted-state dosing (n=3).

Results
The final model described concentration–time profiles after fed and fasted dosing accurately, and estimated the food effect associated with relative bioavailability to 1.18 (95% CI 1.10–1.67).

Conclusions
In this analysis, the effect of a high-fat breakfast compared with a fasted-state administration of a single oral dose of 12 mg ivermectin was minimal.
Genomic Analysis of Dysembryoplastic Neuroepithelial Tumor Spectrum Reveals a Diversity of Molecular Alterations Dysregulating the MAPK and PI3K/mTOR Pathways
Authors: Surrey Lea F , Jain Payal , Zhang Bo , Straka Joshua , Zhao Xiaonan , Harding Brian N , Resnick Adam C , Storm Phillip B , Buccoliero Anna Maria , Genitori Lorenzo , Li Marilyn M , Waanders Angela J , Santi Mariarita 
Published: October 2019

AbstractDysembryoplastic neuroepithelial tumors (DNT) lacking key diagnostic criteria are challenging to diagnose and sometimes fall into the broader category of mixed neuronal-glial tumors (MNGT) or the recently described polymorphous low-grade neuroepithelial tumor of the young (PLNTY). We examined 41 patients with DNT, MNGT, or PLNTY for histologic features, genomic findings, and progression-free survival (PFS). Genomic analysis included sequence and copy number variants and RNA-sequencing. Classic DNT (n = 26) was compared with those with diffuse growth without cortical nodules (n = 15), 6 of which exhibited impressive CD34 staining classifying them as PLNTY. Genomic analysis was complete in 33, with sequence alterations recurrently identified in BRAF, FGFR1, NF1, and PDGFRA, as well as 7 fusion genes involving FGFR2, FGFR1, NTRK2, and BRAF. Genetic alterations did not distinguish between MNGTs, DNTs, or PLNTYs; however, FGFR1 alterations were confined to DNT, and PLNTYs contained BRAF V600E or FGFR2 fusion genes. Analysis of PFS showed no significant difference by histology or genetic alteration; however, numbers were small and follow-up time short. Further molecular characterization of a PLNTY-related gene fusion, FGFR2-CTNNA3, demonstrated oncogenic potential via MAPK/PI3K/mTOR pathway activation. Overall, DNT-MNGT spectrum tumors exhibit diverse genomic alterations, with more than half (19/33) leading to MAPK/PI3K pathway alterations.
From Partisan Media to Misperception: Affective Polarization as Mediator
Authors: Garrett R Kelly , Long Jacob A , Jeong Min Seon 
Published: October 2019

AbstractThis article provides evidence that affective polarization is an important mechanism linking conservative media use to political misperceptions. Partisan media’s potential to polarize is well documented, and there are numerous ways in which hostility toward political opponents might promote the endorsement of inaccurate beliefs. We test this mediated model using data collected via nationally representative surveys conducted during two recent U.S. presidential elections. Fixed effects regression models using three-wave panel data collected in 2012 provide evidence that conservative media exposure contributes to more polarized feelings toward major-party presidential candidates, and this growing favorability gap is associated with misperceptions critical of the Democrats. Further, these effects are more pronounced among Republicans than among Democrats. Cross-sectional analyses using data collected in 2016 provide additional evidence of the mediated relationship. The theoretical and real-world significance of these results are discussed.
Detecting the driving forces underlying the divergence of spruce forests in China: evidence from phytocoenology, morphology and phylogenetics
Authors: Wang Guo-Hong , Zhao Hai-Wei , An Meng , Li He , Zhang Wei-Kang 
Published: October 2019

Abstract

Aims
We aimed to elucidate the driving forces underlying the geographical distribution of spruce forests, as well as the morphological and phylogenetic divergence among spruce species in China.

Methods
One hundred and seventy two sites across the entire range of spruce forests in China (23°–53° N, 75°–134° E, 250–4300 m a.s.l.) were sampled for species composition, geographical coordinates, and topographic and climatic variables. Sixteen spruce taxa, which are naturally distributed in China, were respectively grouped into morphologically defined sections and phylogenetically distinct clades. Multivariate approaches, including two-way indicator species analysis, principal components analysis, detrended correspondence analysis, canonical correspondence analysis (CCA), and partial CCA, were used for data analysis.

Important Findings
The 172 samples grouped into 13 spruce forests, the geographical distributions of which were closely related to climate and geographical location. The variation in species composition explained by the geographical coordinates (32.01%) was significantly higher than that explained by the climatic (27.76%) and topographic variables (23.32%). Of the three morphologically defined sections, sect. Omorica occurred mainly in wetter habitats with a mean annual precipitation of ca. 229 mm and 426 mm higher than the habitats of sect. Casicta and sect. Picea (P &lt; 0.01), respectively. Of the two phylogenetically distinct clades, Clade-II (an older clade) occurred in habitats with warm winters and cool summers whose mean temperature in the coldest month was ca. 8–10°C higher, yet accumulated temperature during the growing season (≥ 5°C) was ca. 297–438°C lower, than the habitats of Clade-III (a younger clade) (P &lt; 0.01). Our data support the hypothesis that geographical location may be a greater determinant of variation in species composition. In addition, moisture conditions tend to be the key determinants that account for the divergence among the morphologically defined sections, while the phylogenetic divergence among spruce species is mainly affected by temperature conditions. While the clades or sections of the spruce species in question carry strong climatic signals, their divergences are subject to different selective pressures.
Physical dosimetry reconstructions of significant radiation exposure at an industrial accelerator facility in Tianjin (China)
Authors: Ruan Shuzhou , Huo Menghui , Su Kaijun , Liu Yulian , Yan Changxin , Zhang Wenyi , Jiao Ling 
Published: October 2019

ABSTRACT
The goal of this thesis is to estimate the physical radiation doses for two victims who were accidently exposed to an industrial electron beam at an industrial accelerator facility on 7 July 7 2016 in Tianjin, China. On the basis of the radiation source parameters, irradiation situation and irradiation time, physical dose reconstruction was carried out at the accident site by using a Bottle-Manikin-Absorption (BOMAB) phantom and an Alderson Radiation Therapy (ART) phantom. With thermoluminscent dosimeters (TLDs), skin estimation was conducted for the feet, calves, upper arms, left side of the body and neck, and the mean dose was estimated to be 14.1 ± 5.6 Gy. The foot and leg skin received the highest dose, which was &gt;16.3 Gy. In addition, the mean dose estimated for the eye lens was 0.18 ± 0.07 Gy. The organ effective dose estimated and the total organs effective dose estimated were 0.46–4.94 mSv and 0.21 Sv, respectively. In the course of the accident, the damage caused by the electron radiation field to the exposed person was mainly to the skin, and the contributions to other radiation-sensitive organs were small. The damage to the organs other than the skin was mainly caused by the X-rays generated by the bremsstrahlung of the electron beam from the environment or the human body.
A Sampling Design for Ordered Populations
Authors: Zhang Xiaofei , Fuller Wayne A 
Published: October 2019

Abstract
We present a sampling algorithm for an ordered population with elements that have a measure of size. The algorithm enables one to select a sample with specified probabilities and with efficiency for the estimated mean between that of one per stratum and that of two per stratum. The algorithm contains a design parameter for the efficiency of the estimated mean relative to the efficiency of the estimated variance of the estimated mean. For a variable highly correlated with the order, it is possible for both the efficiency of the estimated mean and the efficiency of the estimated variance for an intermediate design to be greater than that for the two-per-stratum design. For most studied populations, the variance of the estimated mean declines and the variance of the estimated variance increases as one moves from the two-per-stratum design toward the one-per-stratum design. We illustrate the trade-off between the variance of the estimated mean and the variance of the estimated variance using an autoregressive process. An estimator of the variance of the estimated mean and a replication form for variance estimation are given.
Gastroenterology
Authors: Banerjee Ashis , Jafar Anisa J. N. , Mukherjee Angshuman , Solomonides Christian , Witt Erik 
Published: October 2019

Abstract
This chapter on gastroenterology contains seven clinical Short Answer Questions (SAQs) with explanations and sources for further reading. Possible disorders and accompanying symptoms of gastrointestinal origin that may present in the emergency department include hepatitis A, spontaneous bacterial peritonitis, acute pancreatitis, ulcerative colitis, and haemorrhoids, among others. It will be up to the emergency doctor to assess, diagnose, and decide upon a treatment path for each patient. The cases described in this chapter are all situations any emergency doctor is likely to encounter at some point in his or her career. The material in this chapter will greatly aid revision for the Final FRCEM examination.
Prostaglandin-E2 deficiency during late pregnancy and the associated increase in interleukin-1β derived from periaortic lymph nodes lead to abortion
Authors: Guo Qirui , Li Junhong , Zhong Liang , Cai Han , Wang Huarong , Yan Hao , Xia Guoliang , Kang Youmin , Wang Chao 
Published: October 2019

AbstractProstaglandin E2 (PGE2) is a hormone with many physiological functions. During pregnancy, it is generally believed that there is a high level of PGE2 at the final stage of pregnancy, which induces the contraction of uterine smooth muscle and promotes the occurrence of childbirth. However, we find that high PGE2 levels are present throughout late pregnancy in mice, not just during childbirth, and that PGE2 deficiency induced by indomethacin during late pregnancy causes damage to the placental labyrinth and eventually leads to abortion. Interestingly, the damage is closely related to inflammation, which involves the role of inflammatory factors produced by the periaortic lymph nodes (PLNs) near the uterus. Further, through RNA sequencing, we reveal that PLNs produce a large amount of interleukin-1β (IL-1β) when exposed to PGE2 deficiency, which causes damage to the placental labyrinth, probably via destroying the extracellular matrix. Finally, events leading to abortion following indomethacin administration are effectively prevented by supplementing PGE2 or by PLN removal. These results suggest that high levels of PGE2 during late pregnancy protect fetuses from inflammatory damage related to IL-1β. This work suggests a new role of PGE2 during late pregnancy and may provide potential therapeutic strategies for pathological pregnancy.
ENdb: a manually curated database of experimentally supported enhancers for human and mouse
Authors: Bai Xuefeng , Shi Shanshan , Ai Bo , Jiang Yong , Liu Yuejuan , Han Xiaole , Xu Mingcong , Pan Qi , Wang Fan , Wang Qiuyu , Zhang Jian , Li Xuecang , Feng Chenchen , Li Yanyu , Wang Yuezhu , Song Yiwei , Feng Ke , Li Chunquan 
Published: October 2019

AbstractEnhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Although some enhancer databases have been published, most only focus on enhancers identified by high-throughput experimental techniques. Therefore, it is highly desirable to construct a comprehensive resource of manually curated enhancers and their related information based on low-throughput experimental evidences. Here, we established a comprehensive manually-curated enhancer database for human and mouse, which provides a resource for experimentally supported enhancers, and to annotate the detailed information of enhancers. The current release of ENdb documents 737 experimentally validated enhancers and their related information, including 384 target genes, 263 TFs, 110 diseases and 153 functions in human and mouse. Moreover, the enhancer-related information was supported by experimental evidences, such as RNAi, in vitro knockdown, western blotting, qRT-PCR, luciferase reporter assay, chromatin conformation capture (3C) and chromosome conformation capture-on-chip (4C) assays. ENdb provides a user-friendly interface to query, browse and visualize the detailed information of enhancers. The database is available at http://www.licpathway.net/ENdb.
LncTarD: a manually-curated database of experimentally-supported functional lncRNA–target regulations in human diseases
Authors: Zhao Hongying , Shi Jian , Zhang Yunpeng , Xie Aimin , Yu Lei , Zhang Caiyu , Lei Junjie , Xu Haotian , Leng Zhijun , Li Tengyue , Huang Waidong , Lin Shihua , Wang Li , Xiao Yun , Li Xia 
Published: October 2019

AbstractLong non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.
Sexual Dysfunction: Prevalence and Prognosis in Patients Operated for Degenerative Lumbar Spondylolisthesis
Authors: Chan Andrew K , Bisson Erica F , Fu Kai-Ming , Park Paul , Robinson Leslie C , Bydon Mohamad , Glassman Steven D , Foley Kevin T , Shaffrey Christopher I , Potts Eric A , Shaffrey Mark E , Coric Domagoj , Knightly John J , Wang Michael Y , Slotkin Jonathan R , Asher Anthony L , Virk Michael S , Kerezoudis Panagiotis , Alvi Mohammed A , Guan Jian , Haid Regis W , Mummaneni Praveen V 
Published: October 2019

Abstract

BACKGROUND
There is a paucity of investigation on the impact of spondylolisthesis surgery on back pain-related sexual inactivity.

OBJECTIVE
To investigate predictors of improved sex life postoperatively by utilizing the prospective Quality Outcomes Database (QOD) registry.

METHODS
A total of 218 patients who underwent surgery for grade 1 degenerative lumbar spondylolisthesis were included who were sexually active. Sex life was assessed by Oswestry Disability Index item 8 at baseline and 24-mo follow-up.

RESULTS
Mean age was 58.0 ± 11.0 yr, and 108 (49.5%) patients were women. At baseline, 178 patients (81.7%) had sex life impairment. At 24 mo, 130 patients (73.0% of the 178 impaired) had an improved sex life. Those with improved sex lives noted higher satisfaction with surgery (84.5% vs 64.6% would undergo surgery again, P = .002). In multivariate analyses, lower body mass index (BMI) was associated with improved sex life (OR = 1.14; 95% CI [1.05-1.20]; P < .001). In the younger patients (age < 57 yr), lower BMI remained the sole significant predictor of improvement (OR = 1.12; 95% CI [1.03-1.23]; P = .01). In the older patients (age ≥ 57 yr)—in addition to lower BMI (OR = 1.12; 95% CI [1.02-1.27]; P = .02)—lower American Society of Anesthesiologists (ASA) grades (1 or 2) (OR = 3.7; 95% CI [1.2-12.0]; P = .02) and ≥4 yr of college education (OR = 3.9; 95% CI [1.2-15.1]; P = .03) were predictive of improvement.

CONCLUSION
Over 80% of patients who present for surgery for degenerative lumbar spondylolisthesis report a negative effect of the disease on sex life. However, most patients (73%) report improvement postoperatively. Sex life improvement was associated with greater satisfaction with surgery. Lower BMI was predictive of improved sex life. In older patients—in addition to lower BMI—lower ASA grade and higher education were predictive of improvement.
The effects of the universal metering programme on water consumption, welfare and equity
Authors: Ornaghi Carmine , Tonin Mirco 
Published: October 2019

Abstract
There is consensus that meters are necessary for the promotion of efficient water usage. However, available evidence on the benefits and costs of metering is scant, and often based on small samples. We use data from the first large-scale compulsory metering programme in England to study its impact on consumption, social efficiency and distributional outcomes. We find a decrease in consumption of 22% following meter installation, a considerably higher value than assumed as a policy target. This result implies that, overall, the benefits of metering outweigh its costs. We also document a large heterogeneity in reaction, with many households showing low sensitivity to the new tariff. This novel finding suggests that selective metering, where only more price-sensitive households receive meters, would deliver even higher social welfare. Looking at distributional effects, we find similar reduction in consumption across income groups, although only high-income households gain financially from the new tariff.
Beneath the surface: complexities and groundwater policy-making
Authors: Blomquist William 
Published: October 2019

AbstractGroundwater depletion is a worldwide phenomenon that has prompted calls for improved policy and management. A prominent policy recommendation, especially among economists, is the establishment of well-defined transferable groundwater rights and the promotion of water transfers or markets. Modelled effects and actual results in limited sites show promising potential, but progress has been slow, even in areas of significant need and capacity such as the western United States. This article identifies some of the complexities associated with defining groundwater rights and with managing groundwater aquifers. Those complexities may account to some degree for the incremental and limited progress toward transferable rights. Recent groundwater policy developments in California and other western states are reviewed briefly in light of those complexities.