bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bypassing primary care facilities: health-seeking behavior of middle age and older adults in China
Authors: Li Changle , Chen Zhuo , Khan M. Mahmud 
Published: August 2021

Abstract
Background
With economic development, aging of the population, improved insurance coverage, and the absence of a formal referral system, bypassing primary healthcare facilities appear to have become more common. Chinese patients tend to visit the secondary or tertiary healthcare facilities directly leading to overcrowding at the higher-level facilities. This study attempts to analyze the factors associated with bypassing primary care facilities among patients of age 45 years or older in China.

Methods
Random effects logistic models were used to examine bypassing of primary health facilities among rural-urban patients. Data from 2011 to 2015 waves of the China Health and Retirement Longitudinal Study were used.

Results
Two in five older patients in China bypass primary health centers (PHC) to access care from higher-tier facilities. Urban patients were nearly twice as likely as rural patients to bypass PHC. Regardless of rural-urban residence, our analysis found that a longer travel time to primary facilities compared to higher-tier facilities increases the likelihood of bypassing. Patients with higher educational attainment were more likely to bypass PHCs. In rural areas, patients who reported their health as poor or those who experienced a recent hospitalization had a higher probability of bypassing PHC. In urban areas, older adults (age 65 years or older) were more likely to bypass PHC than the younger group. Patients with chronic conditions like diabetes also had a higher probability of bypassing.

Conclusions
The findings indicate the importance of strengthening the PHCs in China to improve the efficiency and effectiveness of the health system. Significantly lower out-of-pocket costs at the PHC compared to costs at the higher tiers had little or no impact on increasing the likelihood of utilizing the PHCs. Improving service quality, providing comprehensive person-centered care, focusing on family health care needs, and providing critical preventive services will help increase utilization of PHCs as well as the effectiveness and efficiency of the health system.
Genus-level evolutionary relationships of FAR proteins reflect the diversity of lifestyles of free-living and parasitic nematodes
Authors: Yuan Dongjuan , Li Song , Shang Ziyu , Wan Muchun , Lin Yu , Zhang Yanhua , Feng Yaoyu , Xu Lian , Xiao Lihua 
Published: August 2021

Abstract
Background
Nematodes are a widespread and diverse group comprising free-living and parasitic species, some of which have major detrimental effects on crops, animals, and human health. Genomic comparisons of nematodes may help reveal the genetic bases for the evolution of parasitic lifestyles. Fatty acid and retinol-binding proteins (FARs) are thought to be unique to nematodes and play essential roles in their development, reproduction, infection, and possibly parasitism through promoting the uptake, transport, and distribution of lipid and retinol. However, the evolution of FAR family proteins across the phylum Nematoda remains elusive.

Results
We report here the evolutionary relationship of the FAR gene family across nematodes. No FAR was found in Trichocephalida species and Romanomermis culicivorax from Clade I, and FAR could be found in species from Clades III, IV, and V. FAR proteins are conserved in Clade III species and separated into three clusters. Tandem duplications and high divergence events lead to variable richness and low homology of FARs in Steinernema of Clade IVa, Strongyloides of Clade IVb, and intestinal parasitic nematodes from Clades Vc and Ve. Moreover, different richness and sequence variations of FARs in pine wood, root-knot, stem, and cyst nematodes might be determined by reproduction mode or parasitism. However, murine lungworm Angiostrongylus and bovine lungworm Dictyocaulus viviparus from Clade Vd have only 3–4 orthologs of FAR. RNA-seq data showed that far genes, especially far-1 and far-2, were highly expressed in most nematodes. Angiostrongylus cantonensis FAR-1 and FAR-3 have low sequence homology and distinct ligand-binding properties, leading to differences in the cavity volume of proteins. These data indicate that FAR proteins diverged early and experienced low selective pressure to form genus-level diversity. The far genes are present in endophyte or root-colonized bacteria of Streptomyces, Kitasatospora sp., Bacillus subtilis, and Lysobacter, suggesting that bacterial far genes might be derived from plant-parasitic nematodes by horizontal gene transfer.

Conclusions
Data from these comparative analyses have provided insights into genus-level diversity of FAR proteins in the phylum Nematoda. FAR diversification provides a glimpse into the complicated evolution history across free-living and parasitic nematodes.
Engineering of microbial cells for L-valine production: challenges and opportunities
Authors: Gao Hui , Tuyishime Philibert , Zhang Xian , Yang Taowei , Xu Meijuan , Rao Zhiming 
Published: August 2021

AbstractL-valine is an essential amino acid that has wide and expanding applications with a suspected growing market demand. Its applicability ranges from animal feed additive, ingredient in cosmetic and special nutrients in pharmaceutical and agriculture fields. Currently, fermentation with the aid of model organisms, is a major method for the production of L-valine. However, achieving the optimal production has often been limited because of the metabolic imbalance in recombinant strains. In this review, the constrains in L-valine biosynthesis are discussed first. Then, we summarize the current advances in engineering of microbial cell factories that have been developed to address and overcome major challenges in the L-valine production process. Future prospects for enhancing the current L-valine production strategies are also discussed.
Study of cellular heterogeneity and differential dynamics of autophagy in human embryonic kidney development by single-cell RNA sequencing
Authors: Wen-jin Chen , Xiu-wu Pan , Jian Chu , Da Xu , Jia-xin Chen , Wei-jie Chen , Lin-hui Wang , Xin-gang Cui 
Published: August 2021

Abstract
Background
Autophagy is believed to participate in embryonic development, but whether the expression of autophagy-associated genes undergoes changes during the development of human embryonic kidneys remains unknown.

Methods
In this work, we identified 36,151 human renal cells from embryonic kidneys of 9–18 gestational weeks in 16 major clusters by single-cell RNA sequencing (scRNA-seq), and detected 1350 autophagy-related genes in all fetal renal cells. The abundance of each cell cluster in Wilms tumor samples from scRNA-seq and GDC TARGET WT datasets was detected by CIBERSORTx. R package Monocle 3 was used to determine differentiation trajectories. Cyclone tool of R package scran was applied to calculate the cell cycle scores. R package SCENIC was used to investigate the transcriptional regulons. The FindMarkers tool from Seurat was used to calculate DEGs. GSVA was used to perform gene set enrichment analyses. CellphoneDB was utilized to analyze intercellular communication.

Results
It was found that cells in the 13th gestational week showed the lowest transcriptional level in each cluster in all stages. Nephron progenitors could be divided into four subgroups with diverse levels of autophagy corresponding to different SIX2 expressions. SSBpod (podocyte precursors) could differentiate into four types of podocytes (Pod), and autophagy-related regulation was involved in this process. Pseudotime analysis showed that interstitial progenitor cells (IPCs) potentially possessed two primitive directions of differentiation to interstitial cells with different expressions of autophagy. It was found that NPCs, pretubular aggregates and interstitial cell clusters had high abundance in Wilms tumor as compared with para-tumor samples with active intercellular communication.

Conclusions
All these findings suggest that autophagy may be involved in the development and cellular heterogeneity of early human fetal kidneys. In addition, part of Wilms tumor cancer cells possess the characteristics of some fetal renal cell clusters.

Graphical abstract
The regulatory role of antisense lncRNAs in cancer
Authors: Liu Biao , Xiang Wei , Liu Jiahao , Tang Jin , Wang Jinrong , Liu Bin , Long Zhi , Wang Long , Yin Guangming , Liu Jianye 
Published: August 2021

AbstractAntisense long non-coding RNAs (antisense lncRNAs), transcribed from the opposite strand of genes with either protein coding or non-coding function, were reported recently to play a crucial role in the process of tumor onset and development. Functionally, antisense lncRNAs either promote or suppress cancer cell proliferation, migration, invasion, and chemoradiosensitivity. Mechanistically, they exert their regulatory functions through epigenetic, transcriptional, post-transcriptional, and translational modulations. Simultaneously, because of nucleotide sequence complementarity, antisense lncRNAs have a special role on its corresponding sense gene. We highlight the functions and molecular mechanisms of antisense lncRNAs in cancer tumorigenesis and progression. We also discuss the potential of antisense lncRNAs to become cancer diagnostic biomarkers and targets for tumor treatment.
Prediction of exercise sudden death in rabbit exhaustive swimming using deep neural network
Authors: Zhang Yao , Zheng Yineng , Wang Menglu , Guo Xingming 
Published: August 2021

Abstract
Background and objective
Moderate exercise contributes to good health. However, excessive exercise may lead to cardiac fatigue, myocardial damage and even exercise sudden death. Monitoring the heart health has important implication to prevent exercise sudden death. Diagnosis methods such as electrocardiogram, echocardiogram, blood pressure and histological analysis have shown that arrhythmia and left ventricular fibrosis are early warning symptoms of exercise sudden death. Heart sounds (HS) can reflect the changes of cardiac valve, cardiac blood flow and myocardial function. Deep learning has drawn wide attention because of its ability to recognize disease. Therefore, a deep learning method combined with HS was proposed to predict exercise sudden death in New Zealand rabbits. The objective is to develop a method to predict exercise sudden death in New Zealand rabbits.

Methods
This paper proposed a method to predict exercise sudden death in New Zealand rabbits based on convolutional neural network (CNN) and gated recurrent unit (GRU). The weight-bearing exhaustive swimming experiment was conducted to obtain the HS of exercise sudden death and surviving New Zealand rabbits (n = 11/10) at four different time points. Then, the improved Viola integral method and double threshold method were employed to segment HS signals. The segmented HS frames at different time points were taken as the input of a combined CNN and GRU called CNN–GRU network to complete the prediction of exercise sudden death.

Results
In order to evaluate the performance of proposed network, CNN and GRU were used for comparison. When the fourth time point segmented HS frames were taken as input, the result shows that the proposed network has better performance with an accuracy of 89.57%, a sensitivity of 89.38% and a specificity of 92.20%. In addition, the segmented HS frames at different time points were input into CNN–GRU network, and the result shows that with the progress of the experiment, the prediction accuracy of exercise sudden death in New Zealand rabbits increased from 50.98 to 89.57%.

Conclusion
The proposed network shows good performance in classifying HS, which proves the feasibility of deep learning in exploring exercise sudden death. Further, it may have important implications in helping humans explore exercise sudden death.
Associations of acrylamide with non-alcoholic fatty liver disease in American adults: a nationwide cross-sectional study
Authors: Liu Zhening , Wang Jinghua , Chen Shenghui , Xu Chengfu , Zhang Yu 
Published: August 2021

Abstract
Background
Acrylamide (AA) is a toxicant to humans, but the association between AA exposure and the risk of non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, our objective is to examine the cross-sectional association between AA exposure and the risk of NAFLD in American adults.

Methods
A total of 3234 individuals who took part in the National Health and Nutrition Examination Survey (NHANES) 2003–2006 and 2013–2016 were enrolled in the study. NAFLD was diagnosed by the U.S. Fatty Liver Index. Multivariable logistic regression models were applied to estimate the association between AA and NAFLD in the whole group and the non-smoking group.

Results
We discovered that in the whole group, serum hemoglobin adducts of AA (HbAA) were negatively associated with the prevalence of NAFLD after adjustment for various covariables (P for trend < 0.001). Compared with individuals in the lowest HbAA quartiles, the odds ratios (ORs) with 95% confidence intervals (CIs) in the highest HbAA quartiles were 0.61 (0.46–0.81) and 0.57 (0.36–0.88) in the whole group and the non-smoking group, respectively. In contrast, HbGA/HbAA showed a significantly positive correlation with the prevalence of NAFLD in both groups (P for trend < 0.001). In addition, HbGA was not significantly associated with NAFLD in the whole group or the non-smoking group.

Conclusions
HbAA is negatively associated with NAFLD whereas HbGA/HbAA is positively associated with NAFLD in adults in the U.S. Further studies are needed to clarify these relationships.
Long-term personal air pollution exposure and risk for acute exacerbation of idiopathic pulmonary fibrosis
Authors: Tomos Ioannis , Dimakopoulou Konstantina , Manali Effrosyni D. , Papiris Spyros A. , Karakatsani Anna 
Published: August 2021

Abstract
Background
Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL).

Methods
All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O3, NO2, PM2.5 [and PM10, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants’ levels with AE-IPF and inflammatory mediators adjusting for potential confounders.

Results
118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 μg/m3 increase in previous-year mean level of NO2 (OR = 1.52, 95%CI:1.15–2.0, p = 0.003), PM2.5 (OR = 2.21, 95%CI:1.16–4.20, p = 0.016) and PM10 (OR = 2.18, 95%CI:1.15–4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O3 was positively associated with %change of IL-4 (p = 0.014) whilst PM2.5, PM10 and NO2 were inversely associated with %changes of IL-4 (p = 0.003, p = 0.003, p = 0.032) and osteopontin (p = 0.013, p = 0.013, p = 0.085) respectively.

Conclusions
Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.
Joint mapping of cardiovascular diseases: comparing the geographic patterns in incident acute myocardial infarction, stroke and atrial fibrillation, a Danish register-based cohort study 2014–15
Authors: Bihrmann Kristine , Gislason Gunnar , Larsen Mogens Lytken , Ersbøll Annette Kjær 
Published: August 2021

Abstract
Background
Disease mapping aims at identifying geographic patterns in disease. This may provide a better understanding of disease aetiology and risk factors as well as enable targeted prevention and allocation of resources. Joint mapping of multiple diseases may lead to improved insights since e.g. similarities and differences between geographic patterns may reflect shared and disease-specific determinants of disease. The objective of this study was to compare the geographic patterns in incident acute myocardial infarction (AMI), stroke and atrial fibrillation (AF) using the unique, population-based Danish register data.

Methods
Incident AMI, stroke and AF was modelled by a multivariate Poisson model including a disease-specific random effect of municipality modelled by a multivariate conditionally autoregressive (MCAR) structure. Analyses were adjusted for age, sex and income.

Results
The study included 3.5 million adults contributing 6.8 million person-years. In total, 18,349 incident cases of AMI, 28,006 incident cases of stroke, and 39,040 incident cases of AF occurred. Estimated municipality-specific standardized incidence rates ranged from 0.76 to 1.35 for AMI, from 0.79 to 1.38 for stroke, and from 0.85 to 1.24 for AF. In all diseases, geographic variation with clusters of high or low risk of disease after adjustment was seen. The geographic patterns displayed overall similarities between the diseases, with stroke and AF having the strongest resemblances. The most notable difference was observed in Copenhagen (high risk of stroke and AF, low risk of AMI). AF showed the least geographic variation.

Conclusion
Using multiple-disease mapping, this study adds to the results of previous studies by enabling joint evaluation and comparison of the geographic patterns in AMI, stroke and AF. The simultaneous mapping of diseases displayed similarities and differences in occurrence that are non-assessable in traditional single-disease mapping studies. In addition to reflecting the fact that AF is a strong risk factor for stroke, the results suggested that AMI, stroke and AF share some, but not all environmental risk factors after accounting for age, sex and income (indicator of lifestyle and health behaviour).
On the roles of intrinsically disordered proteins and regions in cell communication and signaling
Authors: Bondos Sarah E. , Dunker A. Keith , Uversky Vladimir N. 
Published: August 2021

AbstractFor proteins, the sequence → structure → function paradigm applies primarily to enzymes, transmembrane proteins, and signaling domains. This paradigm is not universal, but rather, in addition to structured proteins, intrinsically disordered proteins and regions (IDPs and IDRs) also carry out crucial biological functions. For these proteins, the sequence → IDP/IDR ensemble → function paradigm applies primarily to signaling and regulatory proteins and regions. Often, in order to carry out function, IDPs or IDRs cooperatively interact, either intra- or inter-molecularly, with structured proteins or other IDPs or intermolecularly with nucleic acids. In this IDP/IDR thematic collection published inCell Communication and Signaling, thirteen articles are presented that describe IDP/IDR signaling molecules from a variety of organisms from humans to fruit flies and tardigrades (“water bears”) and that describe how these proteins and regions contribute to the function and regulation of cell signaling. Collectively, these papers exhibit the diverse roles of disorder in responding to a wide range of signals as to orchestrate an array of organismal processes. They also show that disorder contributes to signaling in a broad spectrum of species, ranging from micro-organisms to plants and animals.
CD146 controls the quality of clinical grade mesenchymal stem cells from human dental pulp
Authors: Ma Lan , Huang Zhiqing , Wu Di , Kou Xiaoxing , Mao Xueli , Shi Songtao 
Published: August 2021

Abstract
Background
Human mesenchymal stem cells from dental pulp (hMSC-DP), including dental pulp stem cells from permanent teeth and exfoliated deciduous teeth, possess unique MSC characteristics such as expression of specific surface molecules and a high proliferation rate. Since hMSC-DP have been applied in numerous clinical studies, it is necessary to establish criteria to evaluate their potency for cell-based therapies.

Methods
We compared stem cell properties of hMSC-DP at passages 5, 10 and 20 under serum (SE) and serum-free (SF) culture conditions. Cell morphology, proliferation capacity, chromosomal stability, surface phenotypic profiles, differentiation and immunoregulation ability were evaluated. In addition, we assessed surface molecule that regulates hMSC-DP proliferation and immunomodulation.

Results
hMSC-DP exhibited a decrease in proliferation rate and differentiation potential, as well as a reduced expression of CD146 when cultured under continuous passage conditions. SF culture conditions failed to alter surface marker expression, chromosome stability or proliferation rate when compared to SE culture. SF-cultured hMSC-DP were able to differentiate into osteogenic, adipogenic and neural cells, and displayed the capacity to regulate immune responses. Notably, the expression level of CD146 showed a positive correlation with proliferation, differentiation, and immunomodulation, suggesting that CD146 can serve as a surface molecule to evaluate the potency of hMSC-DP. Mechanistically, we found that CD146 regulates proliferation and immunomodulation of hMSC-DP through the ERK/p-ERK pathway.

Conclusion
This study indicates that SF-cultured hMSC-DP are appropriate for producing clinical-grade cells. CD146 is a functional surface molecule to assess the potency of hMSC-DP.
Antibiotic resistance, virulence-associated genes analysis and molecular typing of Klebsiella pneumoniae strains recovered from clinical samples
Authors: Mirzaie Amir , Ranjbar Reza 
Published: August 2021

AbstractKlebsiella pneumoniaeis a multidrug-resistant (MDR) opportunistic pathogen that causes nosocomial infections. Virulence analysis and molecular typing as powerful approaches can provide relevant information onK. pneumoniaeinfection. In the current study, antibiotic resistance, virulence-associated genes analysis, as well as molecular typing ofK. pneumoniaestrains were investigated. Out of 505 clinical samples collected from hospitalized patients, 100K. pneumoniaestrains were isolated by standard microbiological methods and subjected to the phenotypic and genotyping analysis. The highest prevalence of resistance was observed against ciprofloxacin (75%), trimethoprim–sulfamethoxazole (73%) and nitrofurantoin (68%). Virulence associated genes includingentB,traT,ybts, magA, iucC, htrAandrmpAwere found in 80%, 62%, 75%, 5%, 30%, 72% and 48%, of the isolates, respectively. The prevalence of biofilm-associated genes includingmrkA, fimH, andmrkDwere equally 88% for all tested isolates. Moreover, the efflux pump genes includingAcrAB, TolCandmdtKwere observed in 41 (41%), 33 (33%) and 26 (26%) of the strains respectively. A significant statistical association was observed between MDR strains and high expression of efflux pump and biofilm genes. TheK. pneumoniaestrains were differentiated into 11 different genetic patterns using the repetitive element sequence-based PCR (rep-PCR) technique. High prevalence of resistance, presence of various virulence factors, high level of efflux pump, and biofilm gene expression in diverse clones ofK. pneumoniaestrains pose an important health issue in clinical settings.