bluuebunny/crossref_metadata_2025 huggingface dataset:
Paediatric autoimmune and autoinflammatory conditions associated with uveitis
Authors: Rahman Najiha , Petrushkin Harry , Solebo Ameenat Lola
Published: November 2020

Childhood uveitis comprises a collection of heterogenous ocular phenotypes which are associated with a diverse range of childhood autoimmune and autoinflammatory disorders. Of these genetic and/or acquired disorders, juvenile idiopathic arthritis is the most common, affecting 30-80% of children with uveitis. Up to a third of children with uveitis have ‘isolated’ idiopathic disease and do not have an associated systemic disease which manifests in childhood. However, uveitis may be the presenting manifestation of disease; thus, the apparently well child who presents with uveitis may have isolated idiopathic disease, but they may have an evolving systemic disorder. The diagnosis of most of the associated disorders is reliant on clinical features rather than serological or genetic investigations, necessitating detailed medical history taking and systemic examination. Adequate control of inflammation is key to good visual outcomes, and multidisciplinary care is key to good broader health outcomes.
Preparation of nanocapsules of palmitic acid with silica shells and their use as a phase change material within microcellular polyurethane foams
Authors: Mortezaei Negin , Alavi Nikje Mir Mohammad
Published: November 2020

A new nanoencapsulated phase change material (PCM) filled polyurethane microcellular foams is reported in this work. Palmitic acid nanocapsules with silica shells (PA@SiO2) is a well-known phase change material synthesized by the sol-gel process are loaded at selected weight ratios into microcellular polyurethane foam. FT-IR spectra revealed successful PA@SiO2 nanocapsules formation and FE-SEM images showed successful core-shell formation with spherical shapes with a mean diameter approximately 350 nm. TGA thermograms showed superior heat resistivity of prepared PCM in comparison with pristine palmitic acid at the final degradation temperature. DSC thermograms showed the heat storage potential of prepared nanoencapsulated PCM as well as corresponding polyurethane nanocomposites. The polyurethane nanocomposites characterized by FT-IR, TGA, FE-SEM as well as DSC methods and data interpreted in detail in order to evaluate the thermal storage capabilities of newly developed nanocomposites.
A Stiffness Variable Passive Compliance Device with Reconfigurable Elastic Inner Skeleton and Origami Shell
Authors: Zhang Zhuang , Chen Genliang , Fan Weicheng , Yan Wei , Kong Lingyu , Wang Hao
Published: November 2020

Devices with variable stiffness are drawing more and more attention with the growing interests of human-robot interaction, wearable robotics, rehabilitation robotics, etc. In this paper, the authors report on the design, analysis and experiments of a stiffness variable passive compliant device whose structure is a combination of a reconfigurable elastic inner skeleton and an origami shell. The main concept of the reconfigurable skeleton is to have two elastic trapezoid four-bar linkages arranged in orthogonal. The stiffness variation generates from the passive deflection of the elastic limbs and is realized by actively switching the arrangement of the leaf springs and the passive joints in a fast, simple and straightforward manner. The kinetostatics and the compliance of the device are analyzed based on an efficient approach to the large deflection problem of the elastic links. A prototype is fabricated to conduct experiments for the assessment of the proposed concept. The results show that the prototype possesses relatively low stiffness under the compliant status and high stiffness under the stiff status with a status switching speed around 80 ms.
Practical Structural Design Approach of Multiconfiguration Planar Single-Loop Metamorphic Mechanism with a Single Actuator
Authors: Yang Qiang , Hao Guangbo , Li Shujun , Wang Hongguang , Li Haiyang
Published: November 2020

As a type of multiconfiguration mechanism that can operate in an under-actuated state, metamorphic mechanisms were proposed more than two decades ago and attracted significant interest. Studies on structural synthesis of metamorphic mechanisms tend to focus more on metamorphic techniques and the structural synthesis of source mechanisms for metamorphic mechanisms. By designing different constraint architectures of metamorphic joints, multistructures can be obtained from the same source metamorphic mechanism. To determine the constraint architectures of metamorphic joints and their different assembly combinations, a kinematic status matrix and a corresponding constraint status matrix are constructed based on the metamorphic cyclogram of a source mechanism. According to the equivalent resistance gradient model and the constraint status matrix, an equivalent resistance matrix for the metamorphic joints is proposed. A structural synthesis matrix of the metamorphic mechanism is then obtained from the equivalent resistance matrix by deducing the constraint form vectors of the metamorphic joints. Furthermore, a kinematic diagram synthesis of the source metamorphic mechanism of a planar single-loop metamorphic mechanism is proposed, which is based on only the 14 one- or zero-degrees-of-freedom linkage groups. The entire structural design method of a metamorphic mechanism is based on the structural synthesis matrix and is presented as a systematic process. Finally, the proposed structural design approach is illustrated by two examples to verify its feasibility and practicality. This study provides an effective method for designing a practical multi-mobility and multiconfiguration planar single-loop metamorphic mechanism with a single actuator.
Knowledge and attitudes of us adults regarding COVID-19
Authors: Hogan Christopher , Atta Massud , Anderson Paul , Stead Tej , Solomon Matthew , Banerjee Paul , Sleigh Bryan , Shivdat John , Webb McAdams Amanda , Ganti Latha
Published: November 2020

This was a survey of the general non-healthcare-worker USA population regarding their knowledge and attitudes toward the COVID-19 pandemic. Almost everyone practiced social distancing. Women were significantly more likely to be worried about contracting the virus than men (65% vs. 43%, p = 0.0272). There was also a linear trend with age, with older Americans being more worried about contracting the virus. Women were also significantly likely to have received the influenza vaccine this past season compared to men (60% vs. 37%, p = .0167). Similarly, women were significantly more likely to get the influenza vaccine next season than men (77% vs. 46%, p = .0014.). Overall, across every age group, geographic part of the USA and gender, more (or the same) Americans plan on getting the influenza vaccine next season compared to last, but not fewer. This may reflect more awareness of preventative health brought on by the COVID-19 pandemic.
A prospective evaluation of the impact of trans-rectal prostate biopsy on the voiding function of patients
Authors: Tolani Musliu Adetola , Ahmed Muhammed , Fidelis Lovely , Awaisu Mudi , Sudi Abdullahi , Nasir Oyelowo , Lawal Ahmad Tijjani , Bello Ahmad , Maitama Hussaini Yusuf
Published: November 2020

Background

Biopsy-related inflammatory edema, urethral blood clots and sphincteric spasm could lead to post-biopsy voiding dysfunction. This study examines the impact of trans-rectal prostate biopsy on the voiding function of patients in our institution.

Methods

Between February 2017 and July 2018, quasi-experimental study was carried out on 68 patients with indication(s) for prostate biopsy. Prior to the biopsy, IPSS (International Prostate Symptoms Score) andQmax(peak flow rate) of each patient were determined. These were re-assessed 7 and 14 days after biopsy, and compared to baseline data. Analysis was done using Statistical Package for Social Science withp < 0.05 considered significant.

Results

Post-biopsy acute urinary retention occurred in 4.4% of the patients. The total IPSS (12.5 vs. 14.7,p = 0.003), IPSS storage sub-score (6.7 vs. 8.3,p = 0.001), bother score (3.3 vs. 3.6,p = 0.025) andQmax(18.7 vs. 15.9 ml/s,p = 0.001) significantly deteriorated from the baseline value on the 7th day post-biopsy. However, there was no significant difference in these variables in comparison with baseline by the 14th day after the biopsy. Patients with moderate IPSS and normalQmaxat baseline had significantly worsened values by the 7th post-biopsy day (p = 0.002 andp = 0.001, respectively) while those with lower baseline bother score had a higher tendency for worsening of their bother score.

Conclusions

Trans-rectal prostate biopsy causes significant worsening of lower urinary tract symptoms and associated deterioration in quality of life, which spontaneously resolved by the second week in the patients.
Correction to: Clustering analysis of tumor metabolic networks
Authors: Manipur Ichcha , Granata Ilaria , Maddalena Lucia , Guarracino Mario R.
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Functional module detection through integration of single-cell RNA sequencing data with protein–protein interaction networks
Authors: Klimm Florian , Toledo Enrique M. , Monfeuga Thomas , Zhang Fang , Deane Charlotte M. , Reinert Gesine
Published: November 2020

Background

Recent advances in single-cell RNA sequencing have allowed researchers to explore transcriptional function at a cellular level. In particular, single-cell RNA sequencing reveals that there exist clusters of cells with similar gene expression profiles, representing different transcriptional states.

Results

In this study, we present scPPIN, a method for integrating single-cell RNA sequencing data with protein–protein interaction networks that detects active modules in cells of different transcriptional states. We achieve this by clustering RNA-sequencing data, identifying differentially expressed genes, constructing node-weighted protein–protein interaction networks, and finding the maximum-weight connected subgraphs with an exact Steiner-tree approach. As case studies, we investigate two RNA-sequencing data sets from human liver spheroids and human adipose tissue, respectively. With scPPIN we expand the output of differential expressed genes analysis with information from protein interactions. We find that different transcriptional states have different subnetworks of the protein–protein interaction networks significantly enriched which represent biological pathways. In these pathways, scPPIN identifies proteins that are not differentially expressed but have a crucial biological function (e.g., as receptors) and therefore reveals biology beyond a standard differential expressed gene analysis.

Conclusions

The introduced scPPIN method can be used to systematically analyse differentially expressed genes in single-cell RNA sequencing data by integrating it with protein interaction data. The detected modules that characterise each cluster help to identify and hypothesise a biological function associated to those cells. Our analysis suggests the participation of unexpected proteins in these pathways that are undetectable from the single-cell RNA sequencing data alone. The techniques described here are applicable to other organisms and tissues.
“Integrative genomic analysis of the bioprospection of regulators and accessory enzymes associated with cellulose degradation in a filamentous fungus (Trichoderma harzianum)”
Authors: Ferreira Filho Jaire A. , Horta Maria Augusta C. , dos Santos Clelton A. , Almeida Deborah A. , Murad Natália F. , Mendes Juliano S. , Sforça Danilo A. , Silva Claudio Benício C. , Crucello Aline , de Souza Anete P.
Published: November 2020

Background

Unveiling fungal genome structure and function reveals the potential biotechnological use of fungi.Trichoderma harzianumis a powerful CAZyme-producing fungus. We studied the genomic regions inT. harzianumIOC3844 containing CAZyme genes, transcription factors and transporters.

Results

We used bioinformatics tools to mine theT. harzianumgenome for potential genomics, transcriptomics, and exoproteomics data and coexpression networks. The DNA was sequenced by PacBio SMRT technology for multiomics data analysis and integration. In total, 1676 genes were annotated in the genomic regions analyzed; 222 were identified as CAZymes inT. harzianumIOC3844. When comparing transcriptome data under cellulose or glucose conditions, 114 genes were differentially expressed in cellulose, with 51 being CAZymes. CLR2, a transcription factor physically and phylogenetically conserved inTrichodermaspp., was differentially expressed under cellulose conditions. The genes induced/repressed under cellulose conditions included those important for plant biomass degradation, including CIP2 of the CE15 family and a copper-dependent LPMO of the AA9 family.

Conclusions

Our results provide new insights into the relationship between genomic organization and hydrolytic enzyme expression and regulation inT. harzianumIOC3844. Our results can improve plant biomass degradation, which is fundamental for developing more efficient strains and/or enzymatic cocktails to produce hydrolytic enzymes.
A structured collaborative approach to intervention design using a modified intervention mapping approach: a case study using the Management and Interventions for Asthma (MIA) project for South Asian children
Authors: Lakhanpaul Monica , Culley Lorraine , Robertson Noelle , Alexander Emma C. , Bird Deborah , Hudson Nicky , Johal Narynder , McFeeters Melanie , Hamlyn-Williams Charlotte , Manikam Logan , Boo Yebeen Ysabelle , Lakhanpaul Maya , Johnson Mark R. D.
Published: November 2020

Background

To describe how using a combined approach of community-based participatory research and intervention mapping principles could inform the development of a tailored complex intervention to improve management of asthma for South Asian (SA) children; Management and Interventions for Asthma (MIA) study.

Methods

A qualitative study using interviews, focus groups, workshops, and modified intervention mapping procedures to develop an intervention planning framework in an urban community setting in Leicester, UK. The modified form of intervention mapping (IM) included: systematic evidence synthesis; community study; families and healthcare professionals study; and development of potential collaborative intervention strategies. Participants in the community study were 63 SA community members and 12 key informants; in-depth semi-structured interviews involved 30 SA families, 14 White British (WB) families and 37 Healthcare Professionals (HCPs) treating SA children living with asthma; prioritisation workshops involved 145 SA, 6 WB and 37 HCP participants; 30 participants in finalisation workshops.

Results

Two key principles were utilised throughout the development of the intervention; community-based participatory research (CBPR) principles and intervention mapping (IM) procedures. The CBPR approach allowed close engagement with stakeholders and generated valuable knowledge to inform intervention development. It accounted for diverse perceptions and experiences with regard to asthma and recognised the priorities of patients and their families/caregivers for service improvement. The ‘ACT on Asthma’ programme was devised, comprising four arms of an intervention strategy: education and training, clinical support, advice centre and raising awareness, to be co-ordinated by a central team.

Conclusions

The modified IM principles utilised in this study were systematic and informed by theory. The combined IM and participatory approach could be considered when tailoring interventions for other clinical problems within diverse communities. The IM approach to intervention development was however resource intensive. Working in meaningful collaboration with minority communities requires specific resources and a culturally competent methodology.
Risk factors associated with renal crescentic formation in pediatric Henoch–Schönlein purpura nephritis: a retrospective cohort study
Authors: Song Yong-Rui , Guo Wan-Liang , Sheng Mao , Lin Qiang , Zhu Xue-Ming , Li Xiao-Zhong
Published: November 2020

Background

The long-term prognosis of Henoch-Schönlein purpura (HSP) depends on the severity of renal involvement, and crescent formation is considered an important risk factor for poor prognosis of Henoch-Schönlein purpura nephritis (HSPN). The objective of this study was to evaluate factors affecting crescent formation in children with HSPN.

Methods

Demographic factors, clinical characteristics, and laboratory data of children with HSPN with or without crescents were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of crescent formation in HSPN.

Results

A total of 191 children with HSPN were enrolled in the study. There were 107 (56%) males and 84 (44%) females, with a median age of 7 years (range: 2 years–15 years). International Study of Kidney Disease in Children (ISKDC) grading was used to divide subjects into two groups: those without glomerular crescent formation (ISKDC grades I–II, n = 146 cases) and those with glomerular crescent formation (ISKDC grades III–V, n = 45 cases). Logistic regression analysis showed that higher urinary white blood cell (WBC) count (OR = 3.300; 95% CI, 1.119–9.739; P = 0.0306) and higher urinary microalbumin/creatinine ratio (ACR) (OR = 25.053; 95% CI, 1.354–463.708; P = 0.0305) were independent risk factors for the formation of crescents in HSPN. The area under the receiver operating characteristic curve of urinary WBC and ACR were 0.753 and 0.698 respectively, with the Hosmer and Lemeshow goodness-of-fit test (P = 0.0669, P > 0.05).

Conclusion

These results suggest that higher urinary WBC count and ACR should be strictly monitored for children with HSPN. Adequate clinical intervention for these risk factors may limit or prevent renal crescent formation.
Malaria in children and women of childbearing age: infection prevalence, knowledge and use of malaria prevention tools in the province of Nyanga, Gabon
Authors: Imboumy-Limoukou Roméo Karl , Maghendji-Nzondo Sydney , Sir-Ondo-Enguier Pater Noster , Niemczura De Carvalho Julie , Tsafack-Tegomo Nathalie Pernelle , Buekens Julie , Okouga Alain Prince , Mouinga-Ondeme Augustin , Kwedy Nolna Sylvie , Lekana-Douki Jean-Bernard
Published: November 2020

Background

There is little information on the social perception of malaria and the use of preventative measures in Gabon, especially in rural areas. Adequate knowledge of malaria prevention and control can help in reducing the burden of malaria among vulnerable groups, particularly pregnant women and children under 5 years old living in malaria-endemic settings. This study was designed to assess the prevalence of malaria and the knowledge and attitude towards this disease in households in Nyanga Province.

Methods

A cross-sectional study was conducted to assess malaria knowledge, prevention practices and prevalence of the malaria infection in five departments of Nyanga Province. Plasmodial infection was diagnosed in children  ≤ 5 years of age and women aged 15-49 years using rapid diagnostic tests. A questionnaire was administered randomly to women aged 15–49 years and to the parents or guardians of children aged ≤ 5 years in 535 households during a 2-week period in March 2018. Overall, the respondents’ socio-demographic characteristics, knowledge of malaria, malaria prevention practices and malaria prevalence were evaluated and compared across the five departments.

Results

Data from a total of 1,307 participants were included in this study, including 631 women of childbearing age (61 of them pregnant) and 676 children. Practically the entire (97.7%) interviewed population had heard about malaria and attributed the cause of malaria to a mosquito bite (95.7%). This survey revealed that the reported rate of reported bed-net use was 73.3%. The study observed an average malaria parasite prevalence of 13.9%. All departmental capitals of Nyanga Province had a significant level of malaria infection except for Mayumba where no plasmodial infection was found.

Conclusion

High malaria prevalence is found in the departmental capital cities of Nyanga Province. This study reveals that respondents have a high knowledge of the malaria symptoms, its mode of transmission and preventive measures. Despite this high level of knowledge of the disease and its preventive measures, the incidence of malaria remains relatively high in this rural community highlighting the need for other types of interventions.
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

Background

This 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.

Methods

A 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.

Results

The 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.

Conclusions

Two 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

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

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

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

Background

Treatment 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.

Methods

This 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.

Results

Fifty 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.

Conclusions

Buparlisib 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 registration

NCT01790932. 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

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

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

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

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

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.
miRNA-126-3p carried by human umbilical cord mesenchymal stem cell enhances endothelial function through exosome-mediated mechanisms in vitro and attenuates vein graft neointimal formation in vivo
Authors: Qu Qingxi , Wang Limei , Bing Weidong , Bi Yanwen , Zhang Chunmei , Jing Xuanxuan , Liu Linghong
Published: November 2020

Background

The aim of this study was to determine whether the combination of MSC implantation with miRNA-126-3p overexpression would further improve the surgical results after vein grafting.

Methods

human umbilical cord MSCs (hucMSCs) and human umbilical vein endothelial cells (HUVECs) were isolated from human umbilical cords and characterized by a series of experiments. Lentivirus vector encoding miRNA-126-3p was transfected into hucMSCs and verified by PCR. We analyzed the miRNA-126-3p-hucMSC function in vascular endothelial cells by using a series of co-culture experiments. miRNA-126-3p-hucMSCs-exosomes were separated from cell culture supernatants and identified by WB and TEM. We validated the role of miRNA-126-3p-hucMSCs-exosomes on HUVECs proliferative and migratory and angiogenic activities by using a series of function experiments. We further performed co-culture experiments to detect downstream target genes and signaling pathways of miRNA-126-3p-hucMSCs in HUVECs. We established a rat vein grafting model, CM-Dil-labeled hucMSCs were injected intravenously into rats, and the transplanted cells homing to the vein grafts were detected by fluorescent microscopy. We performed historical and immunohistochemical experiments to exam miRNA-126-3p-hucMSC transplantation on vein graft neointimal formation and reendothelialization in vitro.

Results

We successfully isolated and identified primary hucMSCs and HUVECs. Primary hucMSCs were transfected with lentiviral vectors carrying miRNA-126-3p at a MOI 75. Co-culture studies indicated that overexpression of miRNA-126-3p in hucMSCs enhanced HUVECs proliferation, migration, and tube formation in vivo. We successfully separated hucMSCs-exosomes and found that miRNA-126-3p-hucMSCs-exosomes can strengthen the proliferative, migratory, and tube formation capacities of HUVECs. Further PCR and WB analysis indicated that, SPRED-1/PIK3R2/AKT/ERK1/2 pathways are involved in this process. In the rat vein arterialization model, reendothelialization analysis showed that transplantation with hucMSCs modified with miRNA-126-3p had a higher reendothelialization of the vein grafts. The subsequent historical and immunohistochemical examination revealed that delivery with miRNA-126-3p overexpressed hucMSCs significantly reduced vein graft intimal hyperplasia in rats.

Conclusion

These results suggest hucMSC-based miRNA-126-3p gene therapy may be a novel option for the treatment of vein graft disease after CABG.
Identification of stress-responsive transcription factors with protein-bound Escherichia coli genomic DNA libraries
Authors: Li Xianqiang , Jiang Xin , Xu Meiying , Fang Yun , Wang Yan , Sun Guoping , Guo Jun
Published: November 2020

Bacteria promoters along with operators are crucial elements in the control of gene expression in microbes in response to environmental stress changes. A genome-wide promoter DNA regulatory library is in demand to be developed for a microbe reporter method to monitor the existence of any given environmental stress substance. In this study, we utilizedEscherichia coli(E. coli) as a model system for the preparation of both cell lysates and genomic DNA fragments. Through enriching protein-bound DNA fragments to construct luciferase reporter libraries, we found that, of 280 clones collected and sequenced, 131 clones contained either the promoter-35 and -10 conservative sequences and/or an operator transcription factor binding sites (TFBS) region. To demonstrate the functionality of the identified clones, five of 131 clones containing LexA binding sequence have been demonstrated to be induced in response to mitomycin C treatment. To evaluate our libraries as a functional screening library, 80 randomly picked up clones were cultured and treated with and without MMC, where two clones were shown to have greater than twofold induction. In addition, two arsenite-responsive clones were identified from 90 clones, one having the well-known ArsR and another having the osmotically inducible lipoprotein (OsmE1). The newly discoveredosmE1has been quantitatively validated to be induced by arsenite treatment with real-time PCR in a dose response and time course manner. This enriching protein-bound DNA luciferase reporter libraries and functional screening facilitate the identification of stress-responsive transcriptional factors in microbes. We developed functional libraries containingE. coligenomic-wide protein-bound DNA as enhancers/operators to regulate downstream luciferase in response to stress.