bluuebunny/crossref_metadata_2025 huggingface dataset:
“Health Technology Assessment in High, Middle and Low-income Countries: New Systematic and Interdisciplinary Approach for Sound Informed-policymaking”
Authors: AlKhaldi Mohammed , Ahmed Sara , Basuoni Aisha Al , Tanner Marcel
Published: December 2020

Technological innovation has a significant role in improving health systems (HSs) and achieving universal health coverage. The World Health Organization (WHO) has declared resolutions on Health Technology Assessment (HTA) and other global organizations emphasized on HTA systems to achieve the Sustainable Development Goals (SDGs). HTA is a modern multidisciplinary decision-making framework linking knowledge and policymaking in order to provide evidence to leaders and ensuring the value of resources by evaluating properties, effects, and/or impacts. The scope of HTA focuses on conducting assessments and analyses to investigate the medical, social, economic, organizational and ethical issues within health and social systems for generating management and technical solutions. HTA is important as it is rapidly growing and is seen as an essential development approach to tackle existing challenges, particularly in developing countries as they share most of the health burdens worldwide. The research aims to comprehensively evaluate HTA within the health and social systems and understand HTA within the national health system with regards to the level of knowledge about HTA, current HTA practices, application, capacity, gaps, and solutions by investigating the perceptions of health systems’ stakeholders in five countries, Canada, Switzerland, Lebanon, Palestine, and Tanzania selected according to the World Bank income classification. The project will last 12 months starts in January 2021 and ends in January 2022. A mixed-methods, quantitative and qualitative, along with a scoping review will be applied. In each country, fifty semi-structured questionnaires, twenty in-depth interviews, and one national focus group discussion will be conducted with health experts, managers, and policymakers selected purposively from the 1st and 2nd levels of the HS structure. Excel, IBM Statistical Package for the Social Sciences (SPSS), and MAXQDA 12 (VERBI GmbH, Berlin) software programs will be used for data management and analysis. The research will form cutting-edge evidence and reference not only for the six countries, but also for the global, regional, and national endeavors with regards to opening a room for HTA best application and optimization based on the produced knowledge from this research. It will reveal lessons learned, determine gaps, and set an applicable strengthening framework for HTA. This framework will eventually aid the decision and policymakers in these countries, and other similar countries and international organizations to build a well-enabled and institutionalized HTA for better universal health coverage, health systems, and multi-sectoral development.
Mechanism of Protective Effect of Xuan-Bai-Cheng-Gi Decoction on LPS-Induced Acute Lung Injury Based on an Integrated Network Pharmacology and RNA-Sequencing Approach
Authors: Zhu Huahe , Wang Shun , Shan Cong , Li Xiaoqian , Tan Bo , Chen Qilong , Yang Yunxiang , Yu Hongji , Yang Aidong
Published: December 2020

Xuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein-protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Validation experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were downregulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.
Clinical Implications of Size of Cavities in Patients With Nontuberculous Mycobacterial Pulmonary Disease: A Single-Center Cohort Study
Authors: Kang Hye-Rin , Hwang Eui Jin , Kim Sung A , Choi Sun Mi , Lee Jinwoo , Lee Chang-Hoon , Yim Jae-Joon , Kwak Nakwon
Published: December 2020

BackgroundThe presence of cavities is a poor prognostic factor in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, little is known about the characteristics of such cavities and their impact on clinical outcomes. The aim of this study is to investigate the size of cavities and their implications on treatment outcomes and mortality in patients with NTM-PD.MethodsWe included patients diagnosed with NTM-PD at Seoul National University Hospital between 1 January 2007 and 31 December 2018. We measured the size of cavities on chest computed tomography scans performed at the time of diagnosis, and used multivariable logistic regression and Cox-proportional hazards regression analysis to investigate the impact of these measurements on treatment outcomes and mortality. ResultsThe study cohort comprised 421 patients (non-cavitary, n=329; cavitary, n=92) with NTM-PD. During a median follow-up period of 49 months, 118 (35.9%) of the 329 patients with non-cavitary and 64 (69.6%) of the 92 patients with cavitary NTM-PD received antibiotic treatment. Cavities >2 cm were associated with worse treatment outcomes (adjusted odds ratio, 0.38; 95% confidence interval [CI], 0.16–0.86) and higher mortality (adjusted hazard ratio, 2.50; 95% CI, 1.04–6.02), while there was no difference in treatment outcomes and mortality between patients with cavities <2 cm and patients with non-cavitary NTM-PD. ConclusionsClinical outcomes are different according to the size of cavities in patients with cavitary NTM-PD; thus the measurement of the size of cavities could help in making clinical decisions.
Clinical Significance of Protrusion Edge Enhancement Using Contrast-Enhanced Magnetic Resonance Imaging in The Conservative Treatment of Giant Lumbar Disc Herniation: A Prospective Observational Study
Authors: Ma Zhijia , Yu Pengfei , Dai Yuxiang , Feng Qiuxiang , Jiang Hong , Li Xiaochun , Yu Zhenhan , Liu Jin Tao
Published: December 2020

Background: Contrast-enhanced lumbar spine magnetic resonance imaging (MRI) was used to predict the efficacy of conservative treatment of giant lumbar disc herniation.Methods: From June 2017 to June 2019, 30 patients with giant lumbar disc herniation with positive and negative bull’s eye signs on contrast-enhanced lumbar spine MRI were assessed to measure differences in the rate of intervertebral disc herniation, rate of protrusion absorption, treatment effect, protrusion rate, and curative effect according to the lumbar Japanese Orthopedic Association (JOA) score before and after treatment.Results: Thirty patients with positive and negative bull’s eye signs (36 men and 24 women) aged 19 to 58 years (mean, 36.37 ± 9.56 years) were included. All patients were followed up for more than 1 year, and at least one MRI review was conducted within 1 year of treatment. The results of the first and final MRI examinations were compared. The protrusion rate was 82.16% ± 14.58% before treatment and 32.20% ± 30.80% after treatment, and the absorptivity of the protrusion was 59.48% ± 38.62%. There was no statistically significant difference in the general data before treatment between the positive and negative groups (P > 0.05). After treatment, the protrusion rate in the positive and negative bull’s eye sign groups was 14.41% ± 14.37% and 49.99% ± 32.70%, respectively (P < 0.05). The absorptivity in the positive and negative bull’s eye sign groups was 83.09% ± 15.54% and 35.87% ± 40.49%, respectively (P < 0.05). There was no statistically significant difference in the JOA score between the two groups before treatment (P > 0.05); however, there was a statistically significant difference in the JOA score between the two groups at 3 months (P < 0.05) and 1 year (P < 0.05) after treatment.Conclusions: Conservative treatment of giant lumbar disc herniation has a satisfactory clinical effect. Contrast-enhanced MRI can be used to predict the resorption of giant lumbar disc herniation. Protrusion resorption is more likely to occur in patients with than without a bull’s eye sign.Trial registration: Chinese Clinical Trial Registry (No. ChiCTR1900022377). Retrospectively registered 08 April 2019.
20-Year Trends in Lipid Intake From Korean Adults: Using Korea National Dietary Survey Data
Authors: Kwon Yong-Seok , Hwang Yu-Jin , Chu Hanna , Ju Seyoung
Published: December 2020

Background: This study was undertaken to analyze 20-year trend regarding the lipid intake of Korean adults according to general characteristics, dietary behavior, food groups, and the Dietary Reference Intakes for Koreans (KDRIs), using KNHANES (Korea National Health and Nutrition Examination Survey) data. Methods: This study selected adults who participated in the 24-hour recall method to investigate the trend of lipid intake for the 20-year period from 1998 to 2018 of the KNHANES. A total of 86,222 individuals with adults aged 19 and over were included in the study. Results: The lipid intake increased significantly in all individuals (+7.34g), men (+9.71g), and women (+4.93g) (p for trend<0.001) from the first to the seventh term. The lipid ratio contributed to energy increased significantly in all individuals (+3.52% percentage points), men (+3.12% percentage points), and women (+3.90% percentage points) over the 20-year period (p for trend<0.001). Lipid intake increased significantly overall as well as by sex, age, residential area, education level (except below 12 years of education), and presence of obesity and abdominal obesity increased over the 20-year period. Total plant and animal lipid intake has increased over the 20-year period from 1998 to 2018. Specifically, the ratio of lipid intake from potatoes, sugars, seeds and nuts, seaweed, beverages, meats, eggs, dairy products, and other animal foods has increased, while that from grains, beans, vegetables, mushrooms, fruits, vegetable oils, fish and shellfish, and animal fats has decreased. Conclusions: The results of this study will aid in the preparation of basic data for nutrition policy and proper nutrition and dietary education with the aim of improving the diets of Koreans nationwide.
Transdiagnostic Comparison of Visual Working Memory Capacity in Bipolar Disorder and Schizophrenia
Authors: Barnes-Scheufler Catherine , Passow Caroline , Rösler Lara , Mayer Jutta , Oertel Viola , Kittel-Schneider Sarah , Matura Silke , Reif Andreas , Bittner Robert A
Published: December 2020

BackgroundImpaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. Methods62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler’s K. ResultsWorking memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. ConclusionsThese findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.
How to promote exclusive breastfeeding in Ireland: a qualitative study on views of Chinese immigrant mothers
Authors: Chen Haoyue , Li Cheng , Zhou Qianling , Cassidy Tanya M. , Younger Katherine M. , Shen Siao , Kearney John M.
Published: December 2020

Background: The exclusive breastfeeding rate in Ireland is very low with extremely slow annual growth. The population of immigrants in Ireland is increasing. Improving exclusive breastfeeding practice among immigrants may contribute to the overall improvement of exclusive breastfeeding rates in Ireland. This study was conducted to elicit suggestions on improving exclusive breastfeeding rate for six months among Chinese immigrants in Ireland. Methods: Fourteen semi-structured in-depth interviews were conducted with Chinese immigrant mothers residing in Ireland, who breastfed exclusively for four to six months. Interviews were recorded and transcribed in Chinese. Data were analyzed using qualitative thematic analysis. Themes were developed through categorization of codes and via in-depth discussion between two researchers.Results: Themes generated from thematic content analyses were 1) suggestions for new mothers: being strong mentally and getting support from family and friends; 2) suggestions for employers: creating a supportive workplace by setting up private room and breastmilk storage facilities; 3) suggestions for health care professionals: advocating breastfeeding in the hospital and addressing cultural differences by recruiting multilingual staff; 4) suggestions for the government: promoting breastfeeding by initiating societal and policy changes. Conclusions: The key findings emerging from this study may be considered in the development of breastfeeding promotion strategies in Ireland. Our findings could also have implications for other English-speaking countries with low rates of exclusive breastfeeding.
A cross-sectional comparison of breastfeeding knowledge, attitudes, and perceived partners’ support among expectant couples in Mekelle Ethiopia
Authors: Gebremariam Kidane , Zelenko Oksana , Mulugeta Afework , Gallegos Danielle
Published: December 2020

Background: Breastfeeding is considered the biological norm and essential to reduce infant morbidity and mortality. Mothers are responsible for breastfeeding but the support of others, including their partners is an influential determinant. The aim of this study was to compare antenatal breastfeeding knowledge, attitudes, and perceived breastfeeding support of expectant couples in Mekelle, Ethiopia. Methods: As part of a randomised controlled trial of an mHealth intervention, 128 couples in their third trimester from three selected health centres in Mekelle city were recruited to participate between September and October 2018. Couples who each had a personal mobile phone, read and spoke Tigrigna, and lived together were included. Baseline data on breastfeeding knowledge, attitudes, and perceived support (breastfeeding savvy, help, appreciation, presence and responsiveness) were collected using previously validated tools through interview by health workers. Result: Compared to mothers, male partners were more likely to indicate their intention to provide breastfeeding appreciation (p=0.02), breastfeeding presence (p=0.002), and breastfeeding responsiveness (p=0.04). The mothers’ prenatal perception of their partners’ intended breastfeeding support was lower than fathers’ perceptions to support their partners. Multiparous mothers had more positive perceptions regarding their partners’ breastfeeding savvy (p=0.03), and breastfeeding help (p=0.02) compared to primiparous mothers.Conclusion: Fathers in Ethiopia are potentially strong supporters of breastfeeding practice. Future breastfeeding interventions should promote the involvement of fathers in breastfeeding and encourage mothers to increase their partners’ involvement in breastfeeding.
TaClpS1, Negatively Regulates Wheat Resistance Against Puccinia striiformis f. sp. tritici
Authors: Yang Qian , Islam Md Ashraful , Cai Kunyan , Tian Shuxin , Liu Yan , Kang Zhensheng , Guo Jun
Published: December 2020

Background: The degradation of intracellular proteins plays an essential role in plant responses to stressful environments. ClpS1 and E3 ubiquitin ligase function as adaptors for selecting target substrates in caseinolytic peptidase (Clp) proteases pathways and the 26S proteasome system, respectively. Currently, the role of E3 ubiquitin ligase in the plant immune response to pathogens is well defined. However, the role of ClpS1 in the plant immune response to pathogens remains unknown. Results: Here, wheat (Triticum aestivum) ClpS1 (TaClpS1) was studied and resulted to encode 161 amino acids, containing a conserved ClpS domain and a chloroplast transit peptide (1-32 aa). TaClpS1 was found to be specifically localized in the chloroplast when expressed transiently in wheat protoplasts. The transcript level of TaClpS1 in wheat was significantly induced during infection by Puccinia striiformis f. sp. tritici (Pst). Knockdown of TaClpS1 via virus-induced gene silencing (VIGS) resulted in an increase in wheat resistance against Pst, accompanied by an increase in the hypersensitive response (HR), accumulation of reactive oxygen species (ROS) and expression of TaPR1 and TaPR2, and a reduction in the number of haustoria, length of infection hypha and infection area of Pst. Furthermore, heterologous expression of TaClpS1 in Nicotiana benthamiana enhanced the infection by Phytophthora parasitica. Conclusions: These results suggest that TaClpS1 negatively regulates the resistance of wheat to Pst.
DNMT1 facilitates proliferation and metastasis of breast cancer by inducing MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis
Authors: Zhu Xiaotao , Lv Lin , Wang Mingzheng , Fan Chen , Lu Xiaofeng , Jin Miaomiao , Li Shuguang , Wang Fan
Published: December 2020

Background: To explore the mechanism by which DNMT1 potentiates proliferation and metastasis of breast cancer by inducing MEG3 promoter methylation in MEG3/miR-494-3p/OTUD4 regulatory axis.Methods: Human breast cancer cell lines (MCF-7, MDA-MB-231, SKBR3) and human breast epithelial cell line MCF10A were selected for the experiments. The expression levels of DNMT1, MEG3, miR-494-3p and OTUD4 were detected by qRT-PCR. Western blot was used to detect the protein expression levels of DNMT1 and OTUD4. ChIP assay was adopted to verify the binding relationship between DNMT1 and MEG3 promoter region. MethPrimer software was applied to identify MEG3 promoter methylation while methylation-specific PCR was conducted to examine its methylation level. The targeted binding sites of miR-494-3p on MEG3/OTUD4 were predicted by bioinformatics and further verified by RNA binding protein immunoprecipitation assay plus dual-luciferase reporter gene assay. Cell proliferative, migratory and invasive abilities were measured by CCK-8, wound healing and Transwell assays.Results: DNMT1 was highly expressed while MEG3 was poorly expressed in breast cancer cells. Silencing DNMT1 inhibited the proliferation, migration and invasion of breast cancer cells by increasing gene expression of MEG3 through demethylation. MEG3 was identified as a ceRNA that regulated miR-494-3p expression via RNA sponging in breast cancer. In addition, miR-494-3p could bind to the 3’-UTR of OTUD4 mRNA, thus negatively regulating OTUD4 expression. A regulator axis formed by MEG3/miR-494-3p/OTUD4 was thus established and identified to have an impact on proliferation, invasion and migration of breast cancer. Moreover, overexpression of MEG3 could suppress tumor growth of breast cancer in vivo.Conclusion: Silencing DNMT1 induced demethylation of MEG3 promoter to promote MEG3 gene expression, in turn inhibiting the expression of miR-494-3p to elevate the expression of its downstream target OTUD4, thus weakening the proliferative, migratory and invasive abilities of breast cancer cells.
SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1
Authors: Tian Cong , Lang Tingyuan , Qiu Jiangfeng , Han Kun , Zhou Lei , Min Daliu , Zhang Zhiqi , Qi Dachuan
Published: December 2020

Background: Cancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive. Methods: Human CRC cell lines and primary human CRC cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels of target genes were examined by qRT-PCR and western blot. The sphere-forming and in vitro migration capacities were determined by sphere formation and transwell assay. The self-renewal was determined by limiting dilution assay. The tumorigenicity and metastasis of cancer cells were examined by xenograft model. The promoter activity was examined by luciferase reporter assay. Nuclear run-on and Chromatin immunoprecipitation-PCR (ChIP-PCR) assay were employed to examine the transcription and protein-DNA interaction. Co-immunoprecipitation assay was used to test protein-protein interaction. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± s.d. and the significance was determined by Student’s t-test.Results: SKP1 was upregulated in CRC-SCs and predicted poor prognosis of colon cancer patients. Overexpression of SKP1 promoted the stemness of CRC cells reflected by increased sphere-forming, migration and self-renewal capacities as well as the expression of CSCs markers. In contrast, SKP1 depletion produced the opposite effects. SKP1 strengthened YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of CRC cells. SKP1 suppressed RASSF1 at both mRNA and protein level. Overexpression of RASSF1 abolished the effect of SKP1 on YAP activity and CRC stemness. Conclusion: Our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells.
Assessment of mitochondrial genomes for heterobranch gastropod phylogenetics
Authors: Varney Rebecca M , Brenzinger Bastian , Malaquias Manuel António E. , Meyer Christopher P. , Schrödl Michael , Kocot Kevin
Published: December 2020

Background Heterobranchia is a diverse clade of marine, freshwater, and terrestrial gastropod molluscs. It includes such disparate taxa as nudibranchs, sea hares, bubble snails, pulmonate land snails and slugs, and a number of (mostly small-bodied) poorly known snails and slugs collectively referred to as the “lower heterobranchs.” Evolutionary relationships within Heterobranchia have been challenging to resolve and the group has been subject to frequent and significant taxonomic revision. Mitochondrial (mt) genomes can be a useful molecular marker for phylogenetics but, to date, sequences have been available for only a relatively small subset of Heterobranchia. Results To assess the utility of mitochondrial genomes for resolving evolutionary relationships within this clade, eleven new mt genomes were sequenced including representatives of several groups of “lower heterobranchs.” Maximum likelihood analyses of concatenated matrices of the thirteen protein coding genes found weak support for most higher-level relationships even after several taxa with extremely high rates of evolution were excluded. Bayesian inference with the CAT+GTR model resulted in a reconstruction that is much more consistent with the current understanding of heterobranch phylogeny. Notably, this analysis recovered Valvatoidea and Orbitestelloidea in a polytomy with a clade including all other heterobranchs, highlighting these taxa as important to understanding early heterobranch evolution. Also, dramatic gene rearrangements were detected within and between multiple clades. However, a single gene order is conserved across the majority of heterobranch clades.Conclusions Analysis of mitochondrial genomes in a Bayesian framework with the site heterogeneous CAT+GTR model resulted in a topology largely consistent with the current understanding of heterobranch phylogeny. However, mitochondrial genomes appear to be too variable to serve as good phylogenetic markers for robustly resolving a number of deeper splits within this clade.
Clinical features of Japanese patients with exacerbations of chronic obstructive pulmonary disease
Authors: Tashiro Hiroki , Kurihara Yuki , Takahashi Koichiro , Sadamatsu Hironori , Haraguchi Tetsuro , Tajiri Ryo , Takamori Ayako , Kimura Shinya , Sueoka-Aragane Naoko
Published: December 2020

BackgroundExacerbations are critical events in chronic pulmonary obstructive disease (COPD). The frequency of COPD exacerbations is associated with the prognosis, including mortality, but no useful biomarker has been established.MethodsThe present retrospective study investigated 481 COPD patients. Clinical features in the stable period were compared between patients who experienced severe exacerbation (n=88, 18.3%) and those who never experienced severe exacerbation (n=393, 81.7%). In the patients who experienced exacerbations, clinical features were also compared between frequent exacerbators (exacerbation rate ≥ 2 times/year, n=27, 30.7%) and infrequent exacerbators (1 time/year, n=61, 69.3%).ResultsCompared to COPD patients who never experienced exacerbations, body mass index (BMI), serum albumin, and pulmonary functions were significantly lower, and the cardiovascular disease comorbidity rate, COPD assessment test score, modified Medical Research Council dyspnea scale, and use of long-term oxygen therapy, long-acting β2 adrenergic agonist therapy, inhaled corticosteroid therapy, and macrolide therapy were significantly higher in COPD patients with exacerbations (all p < 0.01). In patients who experienced exacerbations, frequent exacerbators had significantly lower % forced expiratory volume in 1.0 second and a higher risk of critical exacerbations, percentage of blood eosinophils, history of mechanical ventilation use, and use of long-term oxygen therapy and of macrolide therapy than infrequent exacerbators (all p < 0.01). On multivariate analysis, the percentage of blood eosinophils was the parameter most correlated with exacerbation frequency (β value [95% confidence interval] 1.45 [1.12 – 1.88], p < 0.01).ConclusionBlood eosinophil in the stable period is the factor most correlated with the frequency of severe exacerbations.
Management of unexplained: poly-consultation and hyperfrequency on Primary Health Chilean Attention. A qualitative and exploratory study.
Authors: Sánchez Nicolás Fuster , López Diego Rivera , Retamales Hugo Sir , Pérez Constanza Gómez , Torres Magdalena Rodríguez
Published: December 2020

Background: In Europe, Latin-America, and Asia, poly-consultation has become a complex problem for the management of different healthcare systems. However, in the current literature, little attention has been paid to exploring perspectives of territorial and critical analysis to manage unexplained symptoms.The purpose of this study is to analyze the socio-structural elements that underlie the users’ phenomenon of poly-consultation or hyperfrequency in the Chilean primary healthcare system (PHCS). Methods: This paper represents qualitative data collected as part of an exploratory study that used mixed methods across three metropolitan areas of Santiago, Valparaíso, and Concepción, Chile. The study involved a sample of 24 subjects from administrative and management positions in PHC who were recruited from Family Health Care Centers, considering urban municipalities from the low, medium, and high stratum.The study collected data using one set of semi-standardized interviews during a year. Data analysis used an qualitative content analysis. Results: This article shows that poly-consultant patients provide a critical clinic category to management and mental health model (foreshadowing a social topology base that promotes a determinate unspecific and diffuse experience on users) that cannot be cover by current biomedical models. Data showed the strain of a somatoform clinic category, especially in the clinic and epistemological exercise, and, also, the relevance of particularities of Chile, a country with a mixed health system characteristics and their effects: the naturalization of collective problems managed as individual problems. Conclusions: Results from the study have the potential to inform healthcare professionals and managers of strategies for developing effective and territorially based. We conclude that hyperfrequency and poly-consultation in Chile reveal relevant stratification in the territory who has particularities than could be studied from a quantitative perspective.
Pilot Randomised Evaluation of Singing in Dementia (PRESIDE): protocol for a two-arm, parallel group randomised controlled feasibility study with waiting-list control
Authors: Dowson Becky , Schneider Justine , Guo Boliang , Bath Philip M , McDermott Orii , Haywood Lee J , Orrell Martin
Published: December 2020

BackgroundAs the number of people living with dementia grows, so does the need to provide them with adequate psychosocial support. Many people with dementia live at home with family carers, who also require social and emotional support to cope with their role. Community group singing has received attention for its potential to support people with dementia and their carers. It is postulated that singing can improve cognitive function, strengthen the bonds between care partners, and help to establish social support networks. However, there is a lack of rigorous evidence of singing’s benefits for this population. This study aims to test the feasibility of a randomised controlled trial of community singing in dementia, to pave the way for a larger, conclusive study.MethodsThe PRESIDE study is designed as a two-arm, parallel group randomised trial with a waiting list control. Dyads consisting of a person with dementia (n=80) and their carer (n=80) will be recruited. Each dyad will be randomised either to attend 10 weeks of community group singing sessions straight away, or to wait for three months before attending the sessions. The singing sessions will be led by experienced professional musicians and will last about 90 minutes, including time for socialising. The primary outcome of this study is the attainment of feasibility criteria around recruitment, retention and the acceptability of the waiting list control. Secondary outcomes include the quality of life, mood, cognition, and musical engagement of the person with dementia, and quality of life, mood, and experiences/challenges of the carer. These data will be collected during home visits at baseline, and three and six months post-baseline.DiscussionDespite growing public interest in the positive effects of singing, and encouraging findings from qualitative and non-randomised quantitative studies, there is a lack of rigorous evidence. This is the first randomised controlled trial of community group singing for people with dementia in Europe, to our knowledge. If the results favour a full trial, conclusively demonstrating the effectiveness of group singing could positively affect the opportunities available to community-dwelling people with dementia and their carers.Trial RegistrationUnique identification number in ISRCTN registry: ISRCTN10201482https://www.isrctn.com/ISRCTN10201482. Date registered: 12/05/2020
High-intensity focused ultrasound enhances the cisplatin sensitivity to human non-small cell lung cancer in vitro and in vivo
Authors: Wang Liwei , Fan Huijun , Wang Haiyan , Bai Yunlu , Zhou Wenyan
Published: December 2020

Background: The incidence and mortality of non-small cell lung cancer (NSCLC) rank first among malignant tumors worldwide. Cisplatin (CDDP) is currently the first-line chemotherapy drug used in clinical practice. However, the underlying mechanism that NSCLC cells are resistant to CDDP has not been fully elucidated. Therefore, it is urgent to explore the exact function of chemotherapy resistance and improve the anti-tumor effect of CDDP treatment. Method: We investigated the surviving fraction of H1299 and A549 cells treated with different High-intensity focused ultrasound (HIFU) and various CDDP concentrations. HIFU (400W/cm 2 ) and CDDP (10 μM) were selected to probe the further function in H1299 and A549 cells. Flow cytometry, MTT, and colony formation assays were performed to evaluate the apoptosis and proliferative effect of HIFU and CDDP on NSCLC cells. Transwell assays were used to analyze the migration and invasion abilities of NSCLC cells with HIFU and CDDP treatments. Platinum (Pt) accumulation was further measured in H1299 and A549 cells with different treatments. Finally, An NSCLC patient-derived xenograft model was used to explore the effect of HIFU and CDDP on NSCLC tumor growth. Results: HIFU combined with CDDP can markedly reduce the surviving rate and promote the apoptosis of NSCLC cells. Furthermore, co-treatment with HIFU and CDDP significantly inhibited the proliferation, colony formation, migration, and invasion of NSCLC cells compared to that with any single treatment. Moreover, the combined therapy can effectively promote Pt accumulation in NSCLC cells. Further functional analysis suggested that HIFU combined with CDDP can inhibit tumor growth in an NSCLC patient-derived xenograft model . Finally, the CDDP method effectively upregulated the expression level of apoptosis-related protein, cleaved-PARP, which could be further enhanced by the HIFU treatment. Conclusion: Our results revealed that HIFU enhances the anti-NSCLC effect of CDDP both in vitro and in vivo , providing a promising combination therapy for clinical NSCLC treatment.
Predominantly symplastic phloem unloading of photosynthates maintains efficient starch accumulation in the cassava storage roots (Manihot esculenta Crantz)
Authors: Pan Kun , Lu Cheng , Nie Peixian , Hu Meizhen , Zhou Xincheng , Chen Xin , Wang Wenquan
Published: December 2020

Background: It is well known that cassava (Manihot esculenta Crantz) highly efficiently accumulates starch in its storage roots, but how photosynthates are transported from the leaves to the phloem (especially how they are unloaded into parenchymal cells of storage roots) remains unclear. Methods: Here, we investigated the phloem unloading pattern of sucrose and its impact on the development of cassava storage roots through microstructural and physiological analyses and carboxyfluorescein (CF) and isotope C14 tracing. Expression profiling of genes involved in symplastic and apoplastic transport was performed, and their correlations with storage root yield were determined in populations according to enzyme activity, Western blotting analysis and transcriptome sequencing. Results: Carbohydrates are transported mainly in the form of sucrose, with more than 54.6% present in the stem phloem at any time. Sucrose was predominantly unloaded symplastically from the phloem into storage roots, but there was a shift from apoplastic to symplastic unloading accompanied by the onset of root swelling. Statistical data concerning the microstructure revealed an enrichment of plasmodesmata within sieve, companion and parenchyma cells in the developing storage roots of a cultivar but not in a wild ancestor. Tracing tests with CF verified the existence of a coplastid channel, and [14C]Suc demonstrated that the marked sucrose could rapidly diffuse into root parenchyma cells from phloem cells. The relatively high expression of genes encoding SuSy and associated proteins in the storage roots at the middle and late stages but not in the early stage of storage roots, primary fibrous roots or secondary fibrous roots and the inverse expression pattern of SUTs, CWI and SAI in these corresponding organs supported the presence of a symplastic sucrose unloading pathway. The transcriptome pattern of genes involved in symplastic unloading and their significantly positive correction with starch yield at the population level confirmed that symplastic sucrose transport is vitally important in the development of cassava storage roots. Conclusions: In this study, we revealed a predominantly symplastic phloem unloading pattern of sucrose in cassava storage roots. This pattern is essential for the efficient starch accumulation for sucrose transport between high-yielding varieties and low-yielding wild ancestors.
A Non-Synonymous Variant rs12614 of Complement Factor B Associated with Risk of Chronic Hepatitis B in a Korean Population
Authors: Seo Jung Yeon , Shin Joong Gon , Youn Byeong Ju , Namgoong Suhg , Cheong Hyun Sub , Kim Lyoung Hyo , Kim Ji On , Shin Hyoung Doo , Kim Yoon Jun
Published: December 2020

Background: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.Methods: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1,716 study subjects comprised of 955 CHB patients and 761 population controls. Results: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91×10-10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS. Conclusions: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.
Global transcriptome changes of elongating internode of sugarcane in response to mepiquat chloride
Authors: Chen Rongfa , Fan Yegeng , Zhou Huiwen , Mo Shanping , Zhou Zhongfeng , Yan Haifeng , Luo Ting , Huang Xing , Weng Mengling , Lakshmanan Prakash , Li Yangrui , Qiu Lihang , Wu Jianming
Published: December 2020

Background: Mepiquat chloride (DPC) is an extensively used chemical to control internode growth and compact canopies in cultured plants. Previous studies suggested that DPC could inhibit gibberellin biosynthesis in sugarcane. Unfortunately, the molecular mechanism underlying the suppressive effects of DPC on plant growth is still largely unknown. Results: In the present study, we first obtained the high-quality long transcripts from internode of sugarcane by PacBio Sequel System. A total of 72,671 isoforms with N50 as 3,073 were generated. These long isoforms were used for the following RNA-seq as reference. Subsequently, short reads generated from Illumina Hiseq 4000 platform were used for comparing the differentially expressed genes in DPC and control groups. The transcriptome profiling showed the 6 days post DPC treatment had the most significant changed genes. These genes were related to plant hormone signal transduction and biosynthesis of several metabolites, indicating DPC affected multiple pathways beside depressed gibberellin biosynthesis. The network of DPC on the key stage was illustrated by weighted gene co-expression network analysis (WGCNA). Among the constructed 36 modules, the top positive correlated module with stage of 6 day post spraying DPC was sienna3. Stf0 sulphotransferase, cyclin-like F-box and HOX12 were the hub genes in sienna3 that had high correlation with other genes in this module. The qPCR demonstrated the high accuracy of RNA-seq result. Conclusion: Taken together, we demonstrated the key role of these genes in DPC-induced growth inhibition in sugarcane.
Transcriptome profiling of developing leaf and shoot apices to reveal the molecular mechanism and co-expression genes responsible for the wheat heading date
Authors: Yang Yuxin , Zhang Xueying , Wu Lifen , Zhang Lichao , Liu Guoxiang , Xia Chuan , Liu Xu , Kong Xiuying
Published: December 2020

Background: Wheat is one of the most widely planted crops worldwide. The heading date is important for wheat environmental adaptability; it not only controls flowering time but also determines the yield component in terms of the grain number per spike. Results: In this research, homozygous genotypes with early and late heading dates derived from backcrossed progeny were selected to conduct RNA-seq analysis at the double ridge stage (W2.0) and androgynous primordium differentiation stage (W3.5) of the leaf and apical meristem, respectively. In total, 18,352 differentially expressed genes (DEGs) were identified, many of which are strongly associated with the wheat heading date genes. Gene Ontology (GO) enrichment analysis revealed that carbohydrate metabolism, trehalose metabolic process, photosynthesis, and light reaction are closely related to the flowering time regulation pathway. MapMan metabolic analysis showed that the DEGs mainly functioned in light reaction, hormone signaling, lipid metabolism, secondary metabolism, and nucleotide synthesis. In addition, 1,225 DEGs were annotated to 45 transcription factor gene families, including LFY, SBP, and MADS-box transcription factors that closely related to the flowering time. Weighted gene co-expression network analysis (WGCNA) showed that 16, 336, 446, and 124 DEGs had biological connections with Vrn1-5A, Vrn3-7B, Ppd-1D, and WSOC1, respectively. Furthermore, TraesCS2D02G181400 is a MADS-MIKC transcriptional factor that is co-expressed with Vrn1-5A, which indicates this gene is a potential gene related to the flowering timeConclusions: The RNA-seq analysis enriched the transcriptome data of wheat heading date at the key flower development stages of double ridge (W2.0) and androgynous primordium differentiation (W3.5). Based on the DEGs, the co-expression networks of key flowering time genes in Vrn1-5A, Vrn3-7B, WSOC1, and Ppd-1D were established. Moreover, we discovered a potential candidate flowering time gene TraesCS2D02G181400. Taken together, these results serve as a foundation for further study on the regulatory mechanism of wheat heading date.
Boolean Implication Analysis Unveils Candidate Universal Relationships in Microbiome Data
Authors: Vo Daniella , Singh Shayal Charisma , Safa Sara , Sahoo Debashis
Published: December 2020

Background: Microbiomes consist of bacteria, viruses, and other microorganisms, and are responsible for many different functions in both organisms and the environment. Past analyses of microbiomes focused on using correlation to determine linear relationships between microbes and diseases. Weak correlations due to nonlinearity between microbe pairs may cause researchers to overlook critical components of the data. With the abundance of available microbiome, we need a method that comprehensively studies microbiomes and how they are related to each other.Results: We collected publicly available datasets from human, environment, and animal samples to determine both symmetric and asymmetric Boolean implication relationships between a pair of microbes. We then found relationships that are potentially invariants, meaning they will hold in any microbe community. In other words, if we determine there is a relationship between two microbes, we expect the relationship to hold in almost all contexts. We discovered that around 330,000 pairs of microbes universally exhibit the same relationship in almost all the datasets we studied, thus making them good candidates for invariants. Our results also confirm known biological properties and seem promising in terms of disease diagnosis. Conclusions: Since the relationships are likely universal, we expect them to hold in clinical settings, as well as general populations. If these strong invariants are present in disease settings, it may provide insight into prognostic, predictive, or therapeutic properties of clinically relevant diseases. For example, our results indicate that there is a difference in the microbe distributions between patients who have or do not have IBD, eczema and psoriasis. These new analyses may improve disease diagnosis and drug development in terms of accuracy and efficiency.
Suppression of TCAB1 expression induced cellular senescence by lessening proteasomal degradation of p21 in cancer cells
Authors: Niu Jing , Gao Rui-Qi , Cui Meng-Tian , Zhang Chen-Guang , Li Shen-Tao , Cheng Shan , Ding Wei
Published: December 2020

Background: TCAB1, a.k.a. WRAP53β or WDR79, is an important molecule for the maintenance of Cajal bodies and critically involved in telomere elongation and DNA repair. Upregulation of TCAB1 were discovered in a variety types of cancers. However, the function of TCAB1 in tumor cell senescence remains absent.Methods: The TCAB1 knockdown cell lines were constructed. The expression levels of TCAB1, p21, p16 and p53 were detected by qRT-PCR and western blotting. Staining of senescence-associated β-galactosidase was used to detect senescent cells. The ubiquitination of the p21 was analysed by immunoprecipitatation and in vivo ubiquitination assay. TCGA databases were employed to perform in silico analyses for the mRNA expression of TCAB1, p21, p16 and p53. Results: Here, we discovered that knockdown of TCAB1 induced rapid progression of cellular senescence in A549, H1299 and HeLa cells. In exploiting the mechanism underlining the role of TCAB1 on senescence, we found a significant increase of p21 at the protein levels upon TCAB1 depletion, whereas the p21 mRNA expression was not altered. We verified that TCAB1 knockdown was able to shunt p21 from proteasomal degradation by regulating the ubiquitination of p21. In rescue assays, it was demonstrated that decreasing the expression of p21 or increasing the expression of TCAB1 were able to attenuate the cellular senescence process induced by TCAB1 silencing.Conclusions: This study revealed the importance of TCAB1 for its biological functions in the regulation of cell senescence. Our results will be helpful to understand the mechanisms of senescence in cancer cells, which could provide clues for designing novel strategies for developing effective treatment regimens.