bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of socio-economic, demographic and climate factors on the regional distribution of dengue in the United States and Mexico
Authors: Watts Matthew J. , Kotsila Panagiota , Mortyn P. Graham , Sarto i Monteys Victor , Urzi Brancati Cesira 
Published: November 2020

AbstractBackgroundThis study examines the impact of climate, socio-economic and demographic factors on the incidence of dengue in regions of the United States and Mexico. We select factors shown to predict dengue at a local level and test whether the association can be generalized to the regional or state level. In addition, we assess how different indicators perform compared to per capita gross domestic product (GDP), an indicator that is commonly used to predict the future distribution of dengue.MethodsA unique spatial-temporal dataset was created by collating information from a variety of data sources to perform empirical analyses at the regional level. Relevant regions for the analysis were selected based on their receptivity and vulnerability to dengue. A conceptual framework was elaborated to guide variable selection. The relationship between the incidence of dengue and the climate, socio-economic and demographic factors was modelled via a Generalized Additive Model (GAM), which also accounted for the spatial and temporal auto-correlation.ResultsThe socio-economic indicator (representing household income, education of the labour force, life expectancy at birth, and housing overcrowding), as well as more extensive access to broadband are associated with a drop in the incidence of dengue; by contrast, population growth and inter-regional migration are associated with higher incidence, after taking climate into account. An ageing population is also a predictor of higher incidence, but the relationship is concave and flattens at high rates. The rate of active physicians is associated with higher incidence, most likely because of more accurate reporting. If focusing on Mexico only, results remain broadly similar, however, workforce education was a better predictor of a drop in the incidence of dengue than household income.ConclusionsTwo lessons can be drawn from this study: first, while higher GDP is generally associated with a drop in the incidence of dengue, a more granular analysis reveals that the crucial factors are a rise in education (with fewer jobs in the primary sector) and better access to information or technological infrastructure. Secondly, factors that were shown to have an impact of dengue at the local level are also good predictors at the regional level. These indices may help us better understand factors responsible for the global distribution of dengue and also, given a warming climate, may help us to better predict vulnerable populations on a larger scale.
Health-related quality of life is strongly associated with self-efficacy, self-esteem, loneliness, and stress in 14–15-year-old adolescents: a cross-sectional study
Authors: Mikkelsen Hilde Timenes , Haraldstad Kristin , Helseth Sølvi , Skarstein Siv , Småstuen Milada Cvancarova , Rohde Gudrun 
Published: November 2020

Abstract

Background
To enhance and better understand health-related quality of life (HRQOL) in adolescents, it is important to study factors associated with HRQOL. The present study aimed to assess possible associations between sociodemographic variables, self-efficacy, self-esteem, pain, sleep, loneliness, stress and HRQOL in 14 to 15-year-old adolescents.

Methods
A cross-sectional study was performed among 696 adolescents (14–15 years) in a school-based setting. Sociodemographic variables, self-efficacy, self-esteem, pain, sleep, loneliness and stress were analyzed. The variables were all assessed with well-validated instruments. HRQOL was analyzed using KIDSCREEN 27. Analyses included Chi-square, independent t-tests, Mann–Whitney U tests, linear regression analyses and hierarchical regression analyses. The results from linear regression models were expressed as standardized beta.

Results
The adolescents generally reported high levels of HRQOL. However, girls scored significantly worse on HRQOL, self-efficacy, self-esteem, pain, sleep, loneliness and stress compared to boys. Using hierarchical regression analyses we found that Self-efficacy (beta = 0.11–0.24), Self-esteem: (beta = 0.12–0.21), Loneliness: (beta = − 0.24 to − 0.45) and Stress: (beta = − 0.26 to − 0.34) revealed the strongest associations with the HRQOL dimensions. Sociodemographic-, pain- and sleep related covariates were all significantly associated with some of the KIDSCREEN subscales, however their effect on the outcome was smaller than for the psychosocial variables listed above. Being a girl, not living with both parents, not having both parents working, being absent from school more than 4 days, having pain and having lack of enough sleep were all independently negatively associated with HRQOL.

Conclusions
HRQOL is strongly associated with self-efficacy, self-esteem, loneliness and stress in 14 to 15-year-old adolescents. Our findings indicate that positive psychosocial factors such as self-efficacy and self-esteem might play a buffer role for negative psychosocial factors (e.g. stress) in adolescents. Further, our results show that girls score significantly worse on factors that are associated to HRQOL compared to boys. To improve HRQOL in school-based populations of adolescents, we suggest that future interventions should aim to strengthen self-efficacy and self-esteem. We recommend gender specific interventions.
In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma
Authors: Omstead David T. , Mejia Franklin , Sjoerdsma Jenna , Kim Baksun , Shin Jaeho , Khan Sabrina , Wu Junmin , Kiziltepe Tanyel , Littlepage Laurie E. , Bilgicer Basar 
Published: November 2020

Abstract

Background
Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies.

Methods
In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells. Finally, drug-loaded nanoparticles are tested for long-term efficacy in a month-long in vivo study by tracking tumor size and mouse health.

Results
The targeted nanoparticles are first optimized in vitro and show increased uptake and cytotoxicity over nontargeted nanoparticles, with CD138-targeting showing superior enhancement over CD38-targeted nanoparticles. However, biodistribution and tumor suppression studies established CD38-targeted nanoparticles to have significantly increased in vivo tumor accumulation, tumor cell uptake, and tumor suppression over both nontargeted and CD138-targeted nanoparticles due to the latter’s poor selectivity.

Conclusion
These results both highlight a promising cancer treatment option in CD38-targeted nanoparticles and emphasize that targeting success in vitro does not necessarily translate to success in vivo.
Burden, trends, and risk factors of esophageal cancer in China from 1990 to 2017: an up-to-date overview and comparison with those in Japan and South Korea
Authors: Yang Si , Lin Shuai , Li Na , Deng Yujiao , Wang Meng , Xiang Dong , Xiang Grace , Wang Shuqian , Ye Xianghua , Zheng Yi , Yao Jia , Zhai Zhen , Wu Ying , Hu Jingjing , Kang Huafeng , Dai Zhijun 
Published: November 2020

Abstract

Background
The epidemiology of esophageal cancer (EC) can elucidate its causes and risk factors and help develop prevention strategies. We aimed to provide an overview of the burden, trends, and risk factors of EC in China from 1990 to 2017. We also investigated the differences between China, Japan, and South Korea and discussed the possible causes of the disparities.

Methods
We used the Global Burden of Disease Study 2017 to obtain data on incident cases, deaths, disability-adjusted life-year (DALY) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate of EC in China, Japan, and South Korea from 1990 to 2017. Trend analysis was performed using joinpoint analysis. We measured the associations between ASIR, ASDR, and age-standardized DALY rate and the socio-demographic index (SDI) for 1990–2017. We also analyzed the risk factors associated with EC deaths and DALYs.

Results
China recorded 234,624 (95% uncertainty intervals: 223,240–246,036) incident cases of and 212,586 (202,673–222,654) deaths from EC in 2017. The ASIR and ASDR declined from 1990 to 2017. Until 2017, the ASIR was 12.23, and ASDR was 11.25 per 100,000 persons. The DALYs were 4,464,980 (4,247,816–4,690,846) with an age-standardized rate of 222.58 per 100,000 persons in 2017. The ASIR, ASDR, and age-standardized DALY rate in China were twice those of Japan and South Korea. These three indicators showed a decreasing trend, whereas SDI increased, in all three countries from 1990 to 2017. Tobacco and alcohol use remained the major risk factors for EC death and DALYs, especially for men in China and women in Japan and South Korea. High body mass index (BMI) and low-fruit diet were the main risk factors for women in China.

Conclusions
The incident cases and deaths of EC in China, Japan, and South Korea increased from 1990 to 2017, whereas the ASIR, ASDR, and age-standardized DALY rate declined. China had the greatest burden of EC among three countries. SDI and aging along with tobacco use, alcohol use, high BMI, and low-fruit diet were the main risk factors of death and DALYs and should be paid more attention.
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Authors: Garrido-Castro Ana C. , Saura Cristina , Barroso-Sousa Romualdo , Guo Hao , Ciruelos Eva , Bermejo Begoña , Gavilá Joaquin , Serra Violeta , Prat Aleix , Paré Laia , Céliz Pamela , Villagrasa Patricia , Li Yisheng , Savoie Jennifer , Xu Zhan , Arteaga Carlos L. , Krop Ian E. , Solit David B. , Mills Gordon B. , Cantley Lewis C. , Winer Eric P. , Lin Nancy U. , Rodon Jordi 
Published: November 2020

AbstractBackgroundTreatment options for triple-negative breast cancer remain limited. Activation of the PI3K pathway via loss ofPTENand/orINPP4Bis common. Buparlisib is an orally bioavailable, pan-class I PI3K inhibitor. We evaluated the safety and efficacy of buparlisib in patients with metastatic triple-negative breast cancer.MethodsThis was a single-arm phase 2 study enrolling patients with triple-negative metastatic breast cancer. Patients were treated with buparlisib at a starting dose of 100 mg daily. The primary endpoint was clinical benefit, defined as confirmed complete response (CR), partial response (PR), or stable disease (SD) for ≥ 4 months, per RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. A subset of patients underwent pre- and on-treatment tumor tissue biopsies for correlative studies.ResultsFifty patients were enrolled. Median number of cycles was 2 (range 1–10). The clinical benefit rate was 12% (6 patients, all SD ≥ 4 months). Median PFS was 1.8 months (95% confidence interval [CI] 1.6–2.3). Median OS was 11.2 months (95% CI 6.2–25). The most frequent adverse events were fatigue (58% all grades, 8% grade 3), nausea (34% all grades, none grade 3), hyperglycemia (34% all grades, 4% grade 3), and anorexia (30% all grades, 2% grade 3). Eighteen percent of patients experienced depression (12% grade 1, 6% grade 2) and anxiety (10% grade 1, 8% grade 2). Alterations inPIK3CA/AKT1/PTENwere present in 6/27 patients with available targeted DNA sequencing (MSK-IMPACT), 3 of whom achieved SD as best overall response though none with clinical benefit ≥ 4 months. Of five patients with paired baseline and on-treatment biopsies, reverse phase protein arrays (RPPA) analysis demonstrated reduction of S6 phosphorylation in 2 of 3 patients who achieved SD, and in none of the patients with progressive disease.ConclusionsBuparlisib was associated with prolonged SD in a very small subset of patients with triple-negative breast cancer; however, no confirmed objective responses were observed. Downmodulation of key nodes in the PI3K pathway was observed in patients who achieved SD. PI3K pathway inhibition alone may be insufficient as a therapeutic strategy for triple-negative breast cancer.Trial registrationNCT01790932. Registered on 13 February 2013;NCT01629615. Registered on 27 June 2012.
Parental perspectives long term after neonatal clinical trial participation: a survey
Authors: Salaets Thomas , Lavrysen Emilie , Smits Anne , Vanhaesebrouck Sophie , Rayyan Maissa , Ortibus Els , Toelen Jaan , Claes Laurence , Allegaert Karel 
Published: November 2020

Abstract

Background
Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial.

Methods
Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3–13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales.

Results
Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware).

Conclusions
Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.
De novo assembly of the Brown trout (Salmo trutta m. fario) brain and muscle transcriptome: transcript annotation, tissue differential expression profile and SNP discovery
Authors: Fibla J. , Oromi N. , Pascual-Pons M. , Royo J. L. , Palau A. , Fibla M. 
Published: November 2020

Abstract

Objectives
The Brown trout is a salmonid species with a high commercial value in Europe. Life history and spawning behaviour include resident (Salmo trutta m. fario) and migratory (Salmo trutta m. trutta) ecotypes. The main objective is to apply RNA-seq technology in order to obtain a reference transcriptome of two key tissues, brain and muscle, of the riverine trout Salmo trutta m. fario. Having a reference transcriptome of the resident form will complement genomic resources of salmonid species.

Data description
We generate two cDNA libraries from pooled RNA samples, isolated from muscle and brain tissues of adult individuals of Salmo trutta m. fario, which were sequenced by Illumina technology. Raw reads were subjected to de-novo transcriptome assembly using Trinity, and coding regions were predicted by TransDecoder. A final set of 35,049 non-redundant ORF unigenes were annotated. Tissue differential expression analysis was evaluated by Cuffdiff. A False Discovery Rate (FDR) ≤ 0.01 was considered for significant differential expression, allowing to identify key differentially expressed unigenes. Finally, we have identified SNP variants that will be useful tools for population genomic studies.
DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma
Authors: Alberge Jean-Baptiste , Magrangeas Florence , Wagner Mirko , Denié Soline , Guérin-Charbonnel Catherine , Campion Loïc , Attal Michel , Avet-Loiseau Hervé , Carell Thomas , Moreau Philippe , Minvielle Stéphane , Sérandour Aurélien A. 
Published: November 2020

Abstract

Background
Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals.

Results
Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P < 0.001). Higher levels of 5hmC were found in lower grades of the International Staging System prognostic index (P < 0.05) and tend to associate with a longer overall survival (P < 0.1). From the hydroxymethylome data, we observed that the remaining 5hmC is organized in large domains overlapping with active chromatin marks and chromatin opening. We discovered that 5hmC strongly persists at key oncogenic genes such as CCND1, CCND2 and MMSET and characterized domains that are specifically hydroxymethylated in myeloma subgroups. Novel 5hmC-enriched domains were found at putative enhancers of CCND2 and MYC in newly diagnosed patients.

Conclusions
5hmC level is associated with clinical aspects of MM. Mapping 5hmC at a genome-wide level provides insights into the disease biology directly from genomic DNA, which makes it a potent mark to study epigenetics on large patient cohorts.
Non-allergic severe asthma: is it really always non-allergic? The IDENTIFY project
Authors: Koschel Dirk , Mailänder Claudia , Schwab Sauerbeck Inessa , Schreiber Jens 
Published: November 2020

Abstract

Background
This differential diagnosis of allergic vs non-allergic asthma is typically made on the basis of sensitization to allergens, such that absence of sensitization could result in a patient being managed as having non-allergic asthma. In Germany, the number of specific allergen tests is limited and non-standardized (across clinicians and laboratories), with the potential for false negative diagnoses. IDENTIFY aimed to gain data on sensitizations toward aeroallergens in patients with severe asthma who had tested negative to perennial aeroallergens in previous tests.

Methods
This was a single visit, non-randomized, non-interventional study conducted in 87 centers across Germany. The only inclusion criteria were that patients had to be adults (at least 18 years of age) with a diagnosis of severe asthma (receiving at least Global Initiative for Asthma Step IV therapy), and who had previously tested negative to perennial aeroallergens. Patients were then tested for sensitization to a panel of 35 perennial aeroallergens, with positive sensitization indicated by CAP ≥ 0.35 kU/L.

Results
Of 588 patients recruited, 454 had complete and valid data, and had previously tested negative to perennial aeroallergens. Overall, 43.6% of the analyzed patients tested positive for at least one of the included aeroallergens, with 18.7% testing positive for three or more, and 4.2% positive for more than ten. The five most common sensitizations were to Staphylococcus aureus enterotoxin B, Aspergillus fumigatus, Candida albicans, Dermatophagoides farinae, and Rhizopus nigricans, each of which tested positive in at least 9.7% of the population.

Conclusions
In this group of patients being managed as having non-allergic asthma (and who had all previously tested negative to perennial aeroallergens), a high proportion tested positive to a broad panel of aeroallergens. A diagnosis of allergic asthma therefore cannot be excluded purely on the basis of standard aeroallergen panels.
Circular RNA SIPA1L1 regulates osteoblastic differentiation of stem cells from apical papilla via miR-204-5p/ALPL pathway
Authors: Li Yuzhi , Bian Minxia , Zhou Zhou , Wu Xiao , Ge Xingyun , Xiao Tong , Yu Jinhua 
Published: November 2020

Abstract

Background
Osteogenesis is a complex biological process which requires the coordination of multiple molecular mechanisms. This research aimed to explore the biological role and underlying regulatory mechanism of circSIPA1L1 during the osteogenic differentiation of stem cells from apical papilla (SCAPs).

Methods
EdU retention assay, flow cytometry assay, and CCK-8 assay were used to evaluate the proliferation capacity of SCAPs. Western blot assay, alkaline phosphatase (ALP), and alizarin red staining (ARS) were conducted to investigate the biological roles of circSIPA1L1 and miR-204-5p. Fluorescence in situ hybridization was applied for circSIPA1L1 localization. Dual-luciferase reporter assay was performed to prove the interaction of circSIPA1L1 and miR-204-5p.

Results
CircSIPA1L1 had no significant effect on the proliferative capacity of SCAPs. CircSIPA1L1 promotes osteogenic differentiation of SCAPs by serving as a miRNA sponge for miR-204-5p. Either knockdown of circSIPA1L1 or overexpression of miR-204-5p significantly suppresses osteogenic differentiation of SCAPs.

Conclusions
CircSIPA1L1 upregulates ALPL through targeting miR-204-5p and promotes the osteogenic differentiation of SCAPs.