bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal microbiota domination under extreme selective pressures characterized by metagenomic read cloud sequencing and assembly
Authors: Kang Joyce B. , Siranosian Benjamin A. , Moss Eli L. , Banaei Niaz , Andermann Tessa M. , Bhatt Ami S.
Published: December 2019

Background

Low diversity of the gut microbiome, often progressing to the point of intestinal domination by a single species, has been linked to poor outcomes in patients undergoing hematopoietic cell transplantation (HCT). Our ability to understand how certain organisms attain intestinal domination over others has been restricted in part by current metagenomic sequencing technologies that are typically unable to reconstruct complete genomes for individual organisms present within a sequenced microbial community. We recently developed a metagenomic read cloud sequencing and assembly approach that generates improved draft genomes for individual organisms compared to conventional short-read sequencing and assembly methods. Herein, we applied metagenomic read cloud sequencing to four stool samples collected longitudinally from an HCT patient preceding treatment and over the course of heavy antibiotic exposure.

Results

Characterization of microbiome composition by taxonomic classification of reads reveals that that upon antibiotic exposure, the subject’s gut microbiome experienced a marked decrease in diversity and became dominated by Escherichia coli. While diversity is restored at the final time point, this occurs without recovery of the original species and strain-level composition. Draft genomes for individual organisms within each sample were generated using both read cloud and conventional assembly. Read clouds were found to improve the completeness and contiguity of genome assemblies compared to conventional assembly. Moreover, read clouds enabled the placement of antibiotic resistance genes present in multiple copies both within a single draft genome and across multiple organisms. The occurrence of resistance genes associates with the timing of antibiotics administered to the patient, and comparative genomic analysis of the various intestinal E. coli strains across time points as well as the bloodstream isolate showed that the subject’s E. coli bloodstream infection likely originated from the intestine. The E. coli genome from the initial pre-transplant stool sample harbors 46 known antimicrobial resistance genes, while all other species from the pre-transplant sample each contain at most 5 genes, consistent with a model of heavy antibiotic exposure resulting in selective outgrowth of the highly antibiotic-resistant E. coli.

Conclusion

This study demonstrates the application and utility of metagenomic read cloud sequencing and assembly to study the underlying strain-level genomic factors influencing gut microbiome dynamics under extreme selective pressures in the clinical context of HCT.
A hybrid self-attention deep learning framework for multivariate sleep stage classification
Authors: Yuan Ye , Jia Kebin , Ma Fenglong , Xun Guangxu , Wang Yaqing , Su Lu , Zhang Aidong
Published: December 2019

Background

Sleep is a complex and dynamic biological process characterized by different sleep patterns. Comprehensive sleep monitoring and analysis using multivariate polysomnography (PSG) records has achieved significant efforts to prevent sleep-related disorders. To alleviate the time consumption caused by manual visual inspection of PSG, automatic multivariate sleep stage classification has become an important research topic in medical and bioinformatics.

Results

We present a unified hybrid self-attention deep learning framework, namely HybridAtt, to automatically classify sleep stages by capturing channel and temporal correlations from multivariate PSG records. We construct a new multi-view convolutional representation module to learn channel-specific and global view features from the heterogeneous PSG inputs. The hybrid attention mechanism is designed to further fuse the multi-view features by inferring their dependencies without any additional supervision. The learned attentional representation is subsequently fed through a softmax layer to train an end-to-end deep learning model.

Conclusions

We empirically evaluate our proposed HybridAtt model on a benchmark PSG dataset in two feature domains, referred to as the time and frequency domains. Experimental results show that HybridAtt consistently outperforms ten baseline methods in both feature spaces, demonstrating the effectiveness of HybridAtt in the task of sleep stage classification.
A disease-related gene mining method based on weakly supervised learning model
Authors: Zhang Han , Huo Xueting , Guo Xia , Su Xin , Quan Xiongwen , Jin Chen
Published: December 2019

Background

Predicting disease-related genes is helpful for understanding the disease pathology and the molecular mechanisms during the disease progression. However, traditional methods are not suitable for screening genes related to the disease development, because there are some samples with weak label information in the disease dataset and a small number of genes are known disease-related genes.

Results

We designed a disease-related gene mining method based on the weakly supervised learning model in this paper. The method is separated into two steps. Firstly, the differentially expressed genes are screened based on the weakly supervised learning model. In the model, the strong and weak label information at different stages of the disease progression is fully utilized. The obtained differentially expressed gene set is stable and complete after the algorithm converges. Then, we screen disease-related genes in the obtained differentially expressed gene set using transductive support vector machine based on the difference kernel function. The difference kernel function can map the input space of the original Huntington’s disease gene expression dataset to the difference space. The relation between the two genes can be evaluated more accurately in the difference space and the known disease-related gene information can be used effectively.

Conclusions

The experimental results show that the disease-related gene mining method based on the weakly supervised learning model can effectively improve the precision of the disease-related gene prediction compared with other excellent methods.
Exploring the 2D and 3D structural properties of topologically associating domains
Authors: Liu Tong , Wang Zheng
Published: December 2019

Background

Topologically associating domains (TADs) are genomic regions with varying lengths. The interactions within TADs are more frequent than those between different TADs. TADs or sub-TADs are considered the structural and functional units of the mammalian genomes. Although TADs are important for understanding how genomes function, we have limited knowledge about their 3D structural properties.

Results

In this study, we designed and benchmarked three metrics for capturing the three-dimensional and two-dimensional structural signatures of TADs, which can help better understand TADs’ structural properties and the relationships between structural properties and genetic and epigenetic features. The first metric for capturing 3D structural properties is radius of gyration, which in this study is used to measure the spatial compactness of TADs. The mass value of each DNA bead in a 3D structure is novelly defined as one or more genetic or epigenetic feature(s). The second metric is folding degree. The last metric is exponent parameter, which is used to capture the 2D structural properties based on TADs’ Hi-C contact matrices. In general, we observed significant correlations between the three metrics and the genetic and epigenetic features. We made the same observations when using H3K4me3, transcription start sites, and RNA polymerase II to represent the mass value in the modified radius-of-gyration metric. Moreover, we have found that the TADs in the clusters of depleted chromatin states apparently correspond to smaller exponent parameters and larger radius of gyrations. In addition, a new objective function of multidimensional scaling for modelling chromatin or TADs 3D structures was designed and benchmarked, which can handle the DNA bead-pairs with zero Hi-C contact values.

Conclusions

The web server for reconstructing chromatin 3D structures using multiple different objective functions and the related source code are publicly available at http://dna.cs.miami.edu/3DChrom/.
A probabilistic method for leveraging functional annotations to enhance estimation of the temporal order of pathway mutations during carcinogenesis
Authors: Wang Menghan , Yu Tianxin , Liu Jinpeng , Chen Li , Stromberg Arnold J. , Villano John L. , Arnold Susanne M. , Liu Chunming , Wang Chi
Published: December 2019

Background

Cancer arises through accumulation of somatically acquired genetic mutations. An important question is to delineate the temporal order of somatic mutations during carcinogenesis, which contributes to better understanding of cancer biology and facilitates identification of new therapeutic targets. Although a number of statistical and computational methods have been proposed to estimate the temporal order of mutations, they do not account for the differences in the functional impacts of mutations and thus are likely to be obscured by the presence of passenger mutations that do not contribute to cancer progression. In addition, many methods infer the order of mutations at the gene level, which have limited power due to the low mutation rate in most genes.

Results

In this paper, we develop a Probabilistic Approach for estimating the Temporal Order of Pathway mutations by leveraging functional Annotations of mutations (PATOPA). PATOPA infers the order of mutations at the pathway level, wherein it uses a probabilistic method to characterize the likelihood of mutational events from different pathways occurring in a certain order. The functional impact of each mutation is incorporated to weigh more on a mutation that is more integral to tumor development. A maximum likelihood method is used to estimate parameters and infer the probability of one pathway being mutated prior to another. Simulation studies and analysis of whole exome sequencing data from The Cancer Genome Atlas (TCGA) demonstrate that PATOPA is able to accurately estimate the temporal order of pathway mutations and provides new biological insights on carcinogenesis of colorectal and lung cancers.

Conclusions

PATOPA provides a useful tool to estimate temporal order of mutations at the pathway level while leveraging functional annotations of mutations.
Multiple selective sweeps of ancient polymorphisms in and around LTα located in the MHC class III region on chromosome 6
Authors: Campbell Michael C. , Ashong Bryan , Teng Shaolei , Harvey Jayla , Cross Christopher N.
Published: December 2019

Background

Lymphotoxin-α (LTα), located in the Major Histocompatibility Complex (MHC) class III region on chromosome 6, encodes a cytotoxic protein that mediates a variety of antiviral responses among other biological functions. Furthermore, several genotypes at this gene have been implicated in the onset of a number of complex diseases, including myocardial infarction, autoimmunity, and various types of cancer. However, little is known about levels of nucleotide variation and linkage disequilibrium (LD) in and nearLTα, which could also influence phenotypic variance. To address this gap in knowledge, we examined sequence variation across ~ 10 kilobases (kbs), encompassingLTαand the upstream region, in 2039 individuals from the 1000 Genomes Project originating from 21 global populations.

Results

Here, we observed striking patterns of diversity, including an excess of intermediate-frequency alleles, the maintenance of multiple common haplotypes and a deep coalescence time for variation (dating > 1.0 million years ago), in global populations. While these results are generally consistent with a model of balancing selection, we also uncovered a signature of positive selection in the form of long-range LD on chromosomes with derived alleles primarily in Eurasian populations. To reconcile these findings, which appear to support different models of selection, we argue that selective sweeps (particularly, soft sweeps) of multiple derived alleles in and/or nearLTαoccurred in non-Africans after their ancestors left Africa. Furthermore, these targets of selection were predicted to alter transcription factor binding site affinity and protein stability, suggesting they play a role in gene function. Additionally, our data also showed that a subset of these functional adaptive variants are present in archaic hominin genomes.

Conclusions

Overall, this study identified candidate functional alleles in a biologically-relevant genomic region, and offers new insights into the evolutionary origins of these loci in modern human populations.
Chromosome level assembly and comparative genome analysis confirm lager-brewing yeasts originated from a single hybridization
Authors: Salazar Alex N. , Gorter de Vries Arthur R. , van den Broek Marcel , Brouwers Nick , de la Torre Cortès Pilar , Kuijpers Niels G. A. , Daran Jean-Marc G. , Abeel Thomas
Published: December 2019

Background

The lager brewing yeast,S. pastorianus, is a hybrid betweenS. cerevisiaeandS. eubayanuswith extensive chromosome aneuploidy.S. pastorianusis subdivided into Group 1 and Group 2 strains, where Group 2 strains have higher copy number and a larger degree of heterozygosity forS. cerevisiaechromosomes. As a result, Group 2 strains were hypothesized to have emerged from a hybridization event distinct from Group 1 strains. Current genome assemblies ofS. pastorianusstrains are incomplete and highly fragmented, limiting our ability to investigate their evolutionary history.

Results

To fill this gap, we generated a chromosome-level genome assembly of theS. pastorianusstrain CBS 1483 from Oxford Nanopore MinION DNA sequencing data and analysed the newly assembled subtelomeric regions and chromosome heterozygosity. To analyse the evolutionary history ofS. pastorianusstrains, we developed Alpaca: a method to compute sequence similarity between genomes without assuming linear evolution. Alpaca revealed high similarities between theS. cerevisiaesubgenomes of Group 1 and 2 strains, and marked differences from sequencedS. cerevisiae strains.

Conclusions

Our findings suggest that Group 1 and Group 2 strains originated from a single hybridization involving a heterozygousS. cerevisiaestrain, followed by different evolutionary trajectories. The clear differences between both groups may originate from a severe population bottleneck caused by the isolation of the first pure cultures. Alpaca provides a computationally inexpensive method to analyse evolutionary relationships while considering non-linear evolution such as horizontal gene transfer and sexual reproduction, providing a complementary viewpoint beyond traditional phylogenetic approaches.
Mapping of fire blight resistance in Malus ×robusta 5 flowers following artificial inoculation
Authors: Peil Andreas , Hübert Christine , Wensing Annette , Horner Mary , Emeriewen Ofere Francis , Richter Klaus , Wöhner Thomas , Chagné David , Orellana-Torrejon Carolina , Saeed Munazza , Troggio Michela , Stefani Erika , Gardiner Susan E. , Hanke Magda-Viola , Flachowsky Henryk , Bus Vincent G.M.
Published: December 2019

Background

Although the most common path of infection for fire blight, a severe bacterial disease on apple, is via host plant flowers, quantitative trait loci (QTLs) for fire blight resistance to date have exclusively been mapped following shoot inoculation. It is not known whether the same mechanism underlies flower and shoot resistance.

Results

We report the detection of a fire blight resistance QTL following independent artificial inoculation of flowers and shoots on two F1 segregating populations derived from crossing resistant Malus ×robusta 5 (Mr5) with susceptible ‘Idared’ and ‘Royal Gala’ in experimental orchards in Germany and New Zealand, respectively. QTL mapping of phenotypic datasets from artificial flower inoculation of the ‘Idared’ × Mr5 population with Erwinia amylovora over several years, and of the ‘Royal Gala’ × Mr5 population in a single year, revealed a single major QTL controlling floral fire blight resistance on linkage group 3 (LG3) of Mr5. This QTL corresponds to the QTL on LG3 reported previously for the ‘Idared’ × Mr5 and an ‘M9’ × Mr5 population following shoot inoculation in the glasshouse. Interval mapping of phenotypic data from shoot inoculations of subsets from both flower resistance populations re-confirmed that the resistance QTL is in the same position on LG3 of Mr5 as that for flower inoculation. These results provide strong evidence that fire blight resistance in Mr5 is controlled by a major QTL on LG3, independently of the mode of infection, rootstock and environment.

Conclusions

This study demonstrates for the first time that resistance to fire blight caused by Erwinia amylovora is independent of the mode of inoculation at least in Malus ×robusta 5.
Associations of maternal upper respiratory tract infection/influenza during early pregnancy with congenital heart disease in offspring: evidence from a case-control study and meta-analysis
Authors: Xia Y. Q. , Zhao K. N. , Zhao A. D. , Zhu J. Z. , Hong H. F. , Wang Y. L. , Li S. H.
Published: December 2019

Background

Evidences regarding the associations between maternal upper respiratory tract infection/influenza during pregnancy and the risk of congenital heart disease (CHD) is still controversial. This study was specifically designed to examine the associations by a case-control study and a meta-analysis of the published evidences and our finding.

Methods

A hospital-based case-control study involving 262 children with simple CHD and 262 children with complex CHD, along with 262 control children, was conducted through June, 2016 to December, 2017. All children were aged 0–2 years old. Furthermore, a meta-analysis based on both previously published studies and our case-control study was performed.

Results

In the case-control study, after adjusting for possible confounders, maternal upper respiratory tract infection/influenza during early pregnancy was found to be related to an increased risk of CHD (OR = 3.40 and 95% CI: 2.05–5.62 for simple CHD; OR = 2.39 and 95% CI: 1.47–3.88 for complex CHD). After a meta-analysis, the adverse impact was still kept significant (OR = 1.47 and 95% CI: 1.28–1.67 for simple CHD; OR = 1.44 and 95% CI: 1.14–1.75 for complex CHD). The very similar associations were also observed among single type of CHD, herein, ventricular septal defects (VSD) and tetralogy of fallot (TOF) in the case-control study. In the subsequent meta-analysis, however, the significant association only existed in VSD.

Conclusions

Although there is still conflicting in TOF, the results are overall consistent, which provide new enforced evidence that maternal upper respiratory tract infection/influenza during early pregnancy, in general, play an important role in the occurrence of CHD.
Glycemic control is associated with atrial structural remodeling in patients with type 2 diabetes
Authors: Wang Qing , Wang Jing , Wang Pei , Wang Liaoyuan , Jia Lanting , Ling Xinyu , Xi Wang , Min Jie , Shen Hua , Xiao Jian , Yuan Jinxiang , Wang Zhinong
Published: December 2019

Background

Diabetes mellitus (DM) has been demonstrated to be a strong risk factor for development and perpetuation of atrial fibrillation (AF). However, how DM and glycemic control affect the pathogenesis of AF has not been sufficiently investigated, especially for the atrial structural remodeling.

Methods

A total of 86 patients undergoing coronary artery bypass graft surgery were enrolled in this study, with atrium sample collected in the operation. The patients were divided into the DM group (n = 40) and the control group (n = 46) accordingly. Demographics, clinical data were collected and compared. Echocardiography, Masson staining and Western blotting were conducted to evaluate atrial structural remodeling.

Results

There was no significant difference between the two groups in baseline characteristics (all P > 0.05). Fast blood glucose and HbA1c of DM group were significantly higher than the control group (P < 0.001). Echocardiography results demonstrated that the left atrium diameter (LAD) and left atrium volume index (LAVI) of DM group was significantly higher than the control group (P < 0.001). Masson staining showed that the collagen volume fraction (CVF), a quantitative indicator of fibrosis, was significantly higher in DM patients (P = 0.03). Western blot results indicated that the Collagen I of DM group was more expressed in the DM group than the control group (P < 0.001). Univariate linear regression revealed that the HbA1c level was significantly associated with both LAD (Y = 1.139X + 25.575, P < 0.001, R2 = 0.291) and CVF (Y = 0.444X + 29.648, P = 0.009, R2 = 0.078).

Conclusions

DM was associated with atrial structural remodeling, including atrium enlargement and atrial fibrosis, which might be attributed to poor glycemic control.
The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis
Authors: Jaroszyński Andrzej , Furmaga Jacek , Zapolski Tomasz , Zaborowski Tomasz , Rudzki Sławomir , Dąbrowski Wojciech
Published: December 2019

Background

Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs).

Methods

Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT.

Results

An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement.

Conclusions

RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.
Uptake of intermittent preventive treatment for malaria in pregnancy among women in selected communities of Ebonyi State, Nigeria
Authors: Akpa Christian Obasi , Akinyemi Joshua Odunayo , Umeokonkwo Chukwuma David , Bamgboye Eniola Adetola , Dahiru Tukur , Adebowale Ayo Stephen , Ajayi IkeOluwapo Oyeneye
Published: December 2019

Background

Malaria in pregnancy has adverse effects on maternal and child health. Intermittent preventive treatment (IPTp) with three doses of Sulfadoxine/Pyrimethamine is an effective preventive measure for malaria in pregnancy. However, 24.0% of women use this prophylactic regimen in Ebonyi State. Previous studies have focused on the level of uptake with less attention given to factors influencing uptake. Therefore, we examined the predictors of IPTp uptake in the last pregnancy among women in Ebonyi State, Nigeria.

Methods

This was a community-based cross-sectional study among 340 women of reproductive age selected using multistage sampling technique. A semi-structured interviewer administered questionnaire was used to collect data on socio-demographic characteristics of respondents, IPTp uptake and reasons for not taking IPTp. Adherence was judged adequate if three or more doses of IPTp were taken, otherwise inadequate. Data were analyzed using descriptive statistics, Chi- square test and logistic regression model at 5% level of significance.

Results

Mean age of respondents was 28.8 ± 5.2 years, 96.5% were married, 19.4% had tertiary education, and 11.2% were from polygamous family. Uptake of IPTp was 74.2%. The level of IPTp uptake was 12.5 and 41.0% among women with no formal and tertiary education respectively. A similar pattern of IPTp uptake was observed among women from monogamous (38.0%) and polygamous (39.5%) families. Women education, husband education and family type were associated with uptake of IPTp, however only husband education remained a predictor of uptake. Women whose husband had secondary education (aOR = 4.1, 95%CI: 1.66–10.06) and tertiary education (aOR = 4.8, 95%CI: 1.76–12.90) were more likely to have IPTp uptake than those whose husbands had below secondary education.

Conclusion

Adequate IPTp uptake among women in their last pregnancy was below WHO recommendation. Intervention aimed at improving couple’s education could facilitate increase in IPTp uptake in Ebonyi State.
Development of a new measure for mental retirement; testing of a three-factor structure of mental retirement in different subgroups
Authors: Huijs Jenny J. J. M. , Houtman Irene L. D. , Blonk Roland W. B.
Published: December 2019

Background

The aim of this study is to develop a new measure for the concept of mental retirement and test the construct validity of the measure. Employees who are ‘mentally retired’ are present at their work physically, but have already said their goodbyes mentally. Mental retirement has a three-factor structure: developmental proactivity, work engagement and perceived appreciation.

Methods

We use data from employees (N = 867) of five different organizations in the Netherlands. Mental retirement was assessed with 11 items in an online survey. In addition, socio-demographic characteristics like age, level of education and occupation, were measured. Next to tests of internal consistency, a confirmatory factor analysis (CFA) is performed to test the three-factor structure of mental retirement in this population and in different subgroups (age, education, occupation).

Results

The internal consistency varies from .80 to .94 for the developmental proactivity scale and the work engagement scale, respectively (appreciation was measured with one item). For the CFA, the three-factor model fits the data adequately. Multiple group analyses also shows equal factor loadings in all subgroups, but the mean levels of mental retirement differ across subgroups.

Conclusions

This study confirms the three-factor model of mental retirement in a general group of employees as well as across different subgroups. However, this study only tested the construct validity. Future research should study validity more extensively and be longitudinal in nature. In addition, the causal chain of antecedent variables to mental retirement and its outcomes should be considered. These studies could also focus on the effects of interventions aiming at preventing or decreasing the level of mental retirement in organizations.
Prevalence of burnout and associated factors among general practitioners in Hubei, China: a cross-sectional study
Authors: Gan Yong , Jiang Heng , Li Liqing , Yang Yudi , Wang Chao , Liu Jianxin , Yang Tingting , Opoku Sampson , Hu Sai , Xu Hongbin , Herath Chulani , Chang Yuanyuan , Fang Pengqian , Lu Zuxun
Published: December 2019

Background

High occupational burnout among general practitioners (GPs) is an important challenge to China’s efforts to strengthen its primary healthcare delivery; however, data to help understand this issue are unavailable. This study aimed to investigate the prevalence of burnout and associated factors among GPs.

Methods

A cross-sectional design was used to collect data from December 12, 2014, to March 10, 2015, with a self-administered structured questionnaire from 1015 GPs (response rate, 85.6%) in Hubei Province, Central China. Burnout was measured using a 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS). MBI-HSS scores and frequency were analyzed by the three dimensions of emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Factors associated with burnout among GPs were estimated using a multiple linear regression model.

Results

Of the respondents, 2.46% had a high level of burnout in all three dimensions, 24.83% reported high levels of EE, 6.21% scored high on DP, and 33.99% were at high risk of PA. GPs who were unmarried, had lower levels of job satisfaction, and had been exposed to workplace violence experienced higher levels of burnout. Intriguingly, no statistically significant associations were found between burnout and the duration of GP practice, age, sex, income, practice setting, and professional level.

Conclusion

This is the first study of occupational burnout in Chinese general practice. Burnout is prevalent among GPs in Hubei, China. Interventions aimed at increasing job satisfaction, improving doctor-patient relationships and providing safer workplace environments may be promising strategies to reduce burnout among GPs in Hubei, China.
Patterns of physical activity and health-related quality of life amongst patients with multimorbidity in a multi-ethnic Asian population
Authors: Subramaniam Mythily , Zhang Yunjue , Lau Jue Hua , Vaingankar Janhavi Ajit , Abdin Edimansyah , Chong Siow Ann , Lee Eng Sing
Published: December 2019

Background

The co-occurrence of two or more chronic medical conditions in an individual is defined as multimorbidity. Lifestyle factors, including poor dietary patterns, physical inactivity, tobacco use, and excessive alcohol consumption are key modifiable risk factors that play a role in the development of chronic medical conditions and potentially multimorbidity. The current study aimed to examine the level of physical activity among those with multimorbidity and its association with socio-demographic factors, clinical parameters, and health-related quality of life (HRQoL) among community-dwelling adults attending a primary care clinic in Singapore.

Methods

This cross-sectional study was conducted among patients with multimorbidity between August 2014 and June 2016. Physical activity was measured using the International Physical Activity Questionnaire (IPAQ) Short Form. HRQoL was measured using the EuroQol-5 Dimension (EQ-5D-3 L). Data on clinical parameters including hemoglobin A1c (HbA1C), low-density lipoprotein cholesterol (LDL-C), and blood pressure were collected from patient records. Multivariable logistic regression analysis and linear regression were performed to determine the association between IPAQ and clinical health outcomes, as well as HRQoL measures, respectively.

Results

In all, 932 respondents with multimorbidity were recruited for the study. Of these, 500 (53.8%) had low physical activity, 325 (35.0%) had moderate physical activity, while 104 (11.2%) had high physical activity. Respondents who were insufficiently active had significantly higher odds of being overweight/ obese (OR: 1.5, 95% confidence interval [CI]: 1.1–1.9, p = 0.01) as compared to those who were sufficiently physically active. The multiple linear regression model revealed that insufficient activity level was negatively associated with EQ-5D index score (β = − 0.05, p <  0.001) and the visual analogue scale (β = − 4.4, p <  0.001) measuring HRQoL as compared to sufficient activity levels in respondents with multimorbidity.

Conclusions

The low levels of physical activity among patients with multimorbidity, and its association with overweight status and poorer HRQoL emphasizes the importance of increasing physical activity in this population. Family physicians treating patients with chronic diseases need to continue encouraging and helping individuals to initiate and maintain appropriate physical activity levels.
Assessing effects of personal behaviors and environmental exposure on asthma episodes: a diary-based approach
Authors: Chan Ta-Chien , Hu Tsuey-Hwa , Chu Yen-Hua , Hwang Jing-Shiang
Published: December 2019

Background

Quantifying the effects of personal health behaviors and environmental exposure on asthma flare-ups is a challenge. Most studies have focused on monitoring the symptoms and drug usage for relieving symptoms. In this study, we emphasize the need to understand how personal and environmental conditions are related to the occurrence of asthma symptoms.

Methods

We designed an online health diary platform to collect personal health behaviors from children, their parents and other adults with any allergic diseases including asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis. The participants used mobile devices or computers to record their daily health-related activities such as sleep, exercise, diet, perception of air quality and temperature, and asthma symptoms. The participants also recorded secondhand smoke exposure and the time of activities, which were combined with ambient air quality measurements for calculating personal air pollution exposure. A generalized linear mixed model was used to estimate the effects of the factors.

Results

During the study period (January 2017–June 2017, and October 2017–September 2018), 132 participants provided 25,016 diary entries, and 84 participants had experienced asthma symptoms in 1458 diary entries. The results showed some different risk factors for the minors and adults. For minors, high-intensity exercise, contact with persons with influenza-like illness (ILI) and the perception of hot temperature and bad indoor air quality were associated with the occurrence of asthma episodes. The identified risk factors for the adult participants included having dehumidifiers at home, exposure to secondhand smoke, having bad sleep quality, contact with persons with ILI, not eating fruit and seafood, perceiving cold temperature, bad quality of indoor and outdoor air, and exposure to high concentration of ozone.

Conclusions

The revealed personal risk factors and perceptions of air quality and temperature may provide guidance on behavioral change for people susceptible to asthma to help control acute onset and severe exacerbation of asthma flare-ups.
Substantive molecular and histological changes within the meniscus with tears
Authors: Long Yi , Xie Jingping , Zhang Zhi-Qi , Zhang Ziji , Meng Fangang , He Aishan
Published: December 2019

Background

The meniscus plays a vital role in the normal biomechanics of the knee. However, it is not well studied at the molecular level. The purpose of this study was to determine whether molecular and pathological changes in the meniscal tissue vary depending on the presence or absence of meniscal and/or anterior cruciate ligament tear (ACL).

Methods

Six normal menisci (group A), seven simple torn menisci (group B) and seven torn menisci with concomitant anterior cruciate ligament tears (group C) were collected. We observed the pathological changes in the menisci and used real-time polymerase chain reaction along with immunohistochemistry and in situ hybridisation to examine the levels of ACAN, ADAMTS5, COL10A1, CEBPβ, MMP13 and miR-381-3p, miR-455-3p, miR-193b-3p, miR-92a-3p, respectively. Patients were scored preoperatively and postoperatively using the Lysholm Knee Scoring Scale and International Knee Documentation Committee Subjective Knee Evaluation Form.

Results

Compared with group A, the expression levels of ADAMTS5, COL10A1, CEBPβ, and MMP13 and all the miRNAs were increased while ACAN was down-regulated in groups B and C. Additionally, the gene expression and miRNA levels were higher in group C than that in group B, except for ACAN, which was lower. Several fibrochondrocytes strongly expressed ADAMTS5, CEBPβ, and MMP13 in groups B and C and had high levels of miR-381-3p and miR-455-3p than that in group A. Postoperative Lysholm and IKDC scores were higher in group B than in group C.

Conclusions

Our findings suggest that the meniscus tended to degenerate after it was injured, especially when combined with a torn ACL. The miRNAs investigated in this study might also contribute to meniscus degeneration. Patients with a combined injury patterns might have relatively worse joint function.
Dynamic viscoelastic characterisation of human osteochondral tissue: understanding the effect of the cartilage-bone interface
Authors: Mountcastle Sophie E. , Allen Piers , Mellors Ben O. L. , Lawless Bernard M. , Cooke Megan E. , Lavecchia Carolina E. , Fell Natasha L. A. , Espino Daniel M. , Jones Simon W. , Cox Sophie C.
Published: December 2019

Background

Despite it being known that subchondral bone affects the viscoelasticity of cartilage, there has been little research into the mechanical properties of osteochondral tissue as a whole system. This study aims to unearth new knowledge concerning the dynamic behaviour of human subchondral bone and how energy is transferred through the cartilage-bone interface.

Methods

Dynamic mechanical analysis was used to determine the frequency-dependent (1–90 Hz) viscoelastic properties of the osteochondral unit (cartilage-bone system) as well as isolated cartilage and bone specimens extracted from human femoral heads obtained from patients undergoing total hip replacement surgery, with a mean age of 78 years (N = 5, n = 22). Bone mineral density (BMD) was also determined for samples using micro-computed tomography as a marker of tissue health.

Results

Cartilage storage and loss moduli along with bone storage modulus were found to increase logarithmically (p < 0.05) with frequency. The mean cartilage storage modulus was 34.4 ± 3.35 MPa and loss modulus was 6.17 ± 0.48 MPa (mean ± standard deviation). In contrast, bone loss modulus decreased logarithmically between 1 and 90 Hz (p < 0.05). The storage stiffness of the cartilage-bone-core was found to be frequency-dependent with a mean value of 1016 ± 54.0 N.mm− 1, while the loss stiffness was determined to be frequency-independent at 78.84 ± 2.48 N.mm− 1. Notably, a statistically significant (p < 0.05) linear correlation was found between the total energy dissipated from the isolated cartilage specimens, and the BMD of the isolated bone specimens at all frequencies except at 90 Hz (p = 0.09).

Conclusions

The viscoelastic properties of the cartilage-bone core were significantly different to the tissues in isolation (p < 0.05). Results from this study demonstrate that the functionality of these tissues arises because they operate as a unit. This is evidenced through the link between cartilage energy dissipated and bone BMD. The results may provide insights into the functionality of the osteochondral unit, which may offer further understanding of disease progression, such as osteoarthritis (OA). Furthermore, the results emphasise the importance of studying human tissue, as bovine models do not always display the same trends.
Perioperative fluid dynamics evaluated by bioelectrical impedance analysis predict infectious surgical complications after esophagectomy
Authors: Oya Shuichiro , Yamashita Hiroharu , Iwata Ryohei , Kawasaki Koichiro , Tanabe Asami , Yagi Koichi , Aikou Susumu , Seto Yasuyuki
Published: December 2019

Background

Transthoracic esophagectomy, among the most invasive surgeries, is highly associated with postoperative infectious complications which adversely affect postoperative management including fluid dynamics. The aim of the study is to evaluate the utility of perioperative bioelectrical impedance analysis (BIA) measurements for the patients after transthoracic esophagectomy.

Method

Multi-frequency BIA measurements were conducted in 24 patients undergoing transthoracic esophagectomy preoperatively, at 1 h after surgery, and twice daily for the following 7 days. The amounts of extracellular water (ECW), internal cellular water (ICW), total body water (TBW), and fat-free mass (FFM) were calculated. Changing trends in variables were analyzed, and the patients were subdivided according to the presence of infectious surgical adverse events to identify differences in fluid dynamics.

Results

ECW was the major body fluid compartment showing an increase after surgery, and peaked on postoperative day (POD) 2. Twelve patients experienced infectious complications. The peaks of changes in ECW and ECW/TBW appeared earlier and their values at the highest peak were significantly lower in the group without infectious complications on POD 2. The ICW/FFM value showed a mild decrease as compared to POD1 and then gradually recovered. It was significantly lower even before surgery and showed the most significant stratification on POD2. ECW/TBW of 48% and ICW/FFM of 37% on POD2 were predictive cut-off values for infectious adverse events with high area-under receiver operating characteristic (ROC) curves: 0.80 or higher.

Conclusion

BIA measurements are useful for monitoring fluid retention and may predict infectious complications in the early phase after transthoracic esophagectomy.

Trial registration

Registry name: UMIN-CTR, ID: UMIN000030734, Registered on January 9, 2018, retrospectively registered.
Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis
Authors: Wang Huitao , Liu Jianhe , Fang Kewei , Ke Changxing , Jiang Yongming , Wang Guang , Yang Tongxin , Chen Tao , Shi Xin
Published: December 2019

Background

Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients.

Methods

The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).

Results

Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator’s choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis.

Conclusions

This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.
The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro
Authors: Benson Kathleen F. , Stamets Paul , Davis Renee , Nally Regan , Taylor Alex , Slater Sonya , Jensen Gitte S.
Published: December 2019

Background

The medicinal mushroomTrametes versicolor(Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate.

Methods

Tv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and theTrametes versicolormycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays.

Results

Both aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells.

Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors.

Conclusion

The results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.