bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subgingival microbiota of dogs with healthy gingiva or early periodontal disease from different geographical locations
Authors: Wallis C. , Milella L. , Colyer A. , O’Flynn C. , Harris S. , Holcombe L. J. 
Published: January 2021

AbstractBackgroundPeriodontal disease is the most common oral disease of dogs worldwide and results from a complex interplay between plaque bacteria, the host and environmental factors. Recent studies have enhanced our understanding of the associations between the plaque microbiota and canine periodontal disease. These studies, however, were limited in their geographical reach. Thus associations between the canine oral microbiota and geographical location were investigated by determining the composition of subgingival plaque samples from 587 dogs residing in the United Kingdom (UK), United States of America (USA), China and Thailand using 454-pyrosequencing.ResultsAfter quality filtering 6,944,757 sequence reads were obtained and clustering of these at ≥98% sequence resulted in 280 operational taxonomic units (OTUs) following exclusion of rare OTUs (present at < 0.05% in all four countries). The subgingival plaque from dog populations located in the UK, USA, China and Thailand had a similar composition although the abundance of certain taxa varied significantly among geographical locations. Exploration of the effect of clinical status and age revealed a marked similarity among the bacteria associated with increased age and those associated with gingivitis: Young dogs and those with no gingivitis were dominated by taxa from the phyla Bacteroidetes and Proteobacteria whereas older dogs and those with moderate gingivitis were dominated by members of the Firmicutes. The plaque microbiota of small breed dogs was found to significantly differ to medium and large breeds and was dominated by species belonging to the Firmicutes.ConclusionsThe bacterial associations with health, gingivitis and periodontitis were conserved across dogs from the UK, USA, China and Thailand. These bacterial signatures of periodontal health and disease have potential as biomarkers for disease detection.
DNA methylation abnormalities of imprinted genes in congenital heart disease: a pilot study
Authors: Chang Shaoyan , Wang Yubo , Xin Yu , Wang Shuangxing , Luo Yi , Wang Li , Zhang Hui , Li Jia 
Published: January 2021

Abstract
Background
Congenital heart disease (CHD) is resulted from the interaction of genetic aberration and environmental factors. Imprinted genes, which are regulated by epigenetic modifications, are essential for the normal embryonic development. However, the role of imprinted genes in the etiology of CHD remains unclear.

Methods
After the samples were treated with bisulfate salt, imprinted genes methylation were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. T test and One-way ANOVA were performed to evaluate the differences among groups. Odds ratios (ORs) were performed to evaluate the incidence risk of CHD in relation to methylation levels.

Results
We investigated the alterations of imprinted gene germline differential methylation regions (gDMRs) methylation in patients with CHD. Eighteen imprinted genes that are known to affect early embryonic development were selected and the methylation modification genes were detected by massarray in 27 CHD children and 28 healthy children. Altered gDMR methylation level of 8 imprinted genes was found, including 2 imprinted genes with hypermethylation of GRB10 and MEST and 6 genes with hypomethylation of PEG10, NAP1L5, INPP5F, PLAGL1, NESP and MEG3. Stratified analysis showed that the methylation degree of imprinted genes was different in different types of CHD. Risk analysis showed that 6 imprinted genes, except MEST and NAP1L5, within a specific methylation level range were the risk factors for CHD

Conclusion
Altered methylation of imprinted genes is associated with CHD and varies in different types of CHD. Further experiments are warranted to identify the methylation characteristics of imprinted genes in different types of CHD and clarify the etiologies of imprinted genes in CHD.
TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda
Authors: Kalungi Allan , Kinyanda Eugene , Womersley Jacqueline S. , Joloba Moses L. , Ssembajjwe Wilber , Nsubuga Rebecca N. , Kaleebu Pontiano , Levin Jonathan , Kidd Martin , Seedat Soraya , Hemmings Sian M. J. 
Published: January 2021

Abstract
Background
Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5–11 years) and adolescents (aged 12–17 years).

Results
We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months.

Conclusions
TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.
Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report
Authors: Benbouchta Yahya , Cherkaoui Jaouad Imane , Tazi Habiba , Elorch Hamza , Ouhenach Mouna , Zrhidri Abdelali , Sadki Khalid , Sefiani Abdelaziz , Lyahyai Jaber , Berraho Amina 
Published: January 2021

Abstract
Background
Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution.

Case presentation
In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family.

Conclusions
This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.
Visceral adiposity index is associated with lung function impairment: a population-based study
Authors: He Sunyue , Yang Jie , Li Xiaoyong , Gu Hongxia , Su Qing , Qin Li 
Published: January 2021

Abstract
Background
The effects of visceral adiposity on decreased lung function have drawn much attention. Recently, the visceral adiposity index (VAI) has been proposed as a visceral fat distribution and dysfunction marker. However, the relationship between the VAI and lung function has not been investigated. The objective of the study was to analyze the association between the VAI and lung function and evaluate the potential of VAI as a predictor of lung function.

Methods
We collected data from a population-based study of 1786 subjects aged 40 years or older. All subjects completed a questionnaire and underwent anthropometric measurements and laboratory tests. Linear and logistic regression models were developed to assess the association between the VAI and lung function.

Results
The VAI was inversely related to FVC%predicted in men and negatively associated with both FVC%predicted and FEV1%predicted in women. In the linear regression analysis, the decrease in FVC%predicted associated with each 10% increase in the VAI was 1.127% in men and 1.943% in women; the decrease in FEV1%predicted associated with each 10%increase in the VAI was 0.663% in men and 1.738% in women. Further regression analysis revealed that the VAI was positively correlated with FVC and FEV1 impairment in women.

Conclusions
We were the first to show a clear correlation between the VAI and lung function impairment in the Chinese population. The VAI could be a simple and reliable approach in daily practice, and individuals, especially women with a high VAI, should receive additional screening and preventive interventions for respiratory disease.
Happy hypoxemia, or blunted ventilation?
Authors: Ora Josuel , Rogliani Paola , Dauri Mario , O’Donnell Denis 
Published: January 2021

AbstractHappy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to hypoxemia, but is more closely related to inspiratory drive and mechanical alterations. The lack of dyspnoea in the early stages of the disease is likely related to the absence of increased inspiratory drive due to compensatory mechanisms of hypoxemia, while in the advanced stages there is no evidence of a lack of dyspnoea in COVID-19 patients.
Outcomes associated with comorbid diabetes among patients with COPD exacerbation: findings from the ACURE registry
Authors: Mao Xihua , Liang Chen , Niu Hongtao , Dong Fen , Huang Ke , Chen Yahong , Huang Kewu , Zhan Qingyuan , Zhang Yaowen , Huang Yin , Yang Ting , Wang Chen 
Published: January 2021

Abstract
Background
Diabetes is a common comorbidity among patients with exacerbation of chronic obstructive pulmonary disease (AECOPD). Diabetes has been reported to be associated with length of stay (LOS), death, and cost among AECOPD patients. However, most studies are retrospective or have small sample sizes. The association for cost has not been researched using diabetes as a main analytic factor. This study aimed to fill gaps mentioned above, to compare basic characteristics between the diabetic and non-diabetic group, and to detect associations between diabetes and clinical outcomes among patients hospitalized with AECOPD.

Methods
A total of 5334 AECOPD patients, classified into diabetic and non-diabetic group, were included from a prospective multicenter patient registry study. Generalized linear regression and logistic regression were separately used for the association between diabetes and direct hospitalization cost and the association between diabetes and LOS.

Results
Generally, diabetic patients had a more severe profile, including being older, more overweight or obese, having more former smokers, more emergency room visits in the past 12 months, and more comorbidities occurrence. Diabetic patients also had worse clinical outcomes, including higher cost and longer LOS. Additionally, the generalized linear regression indicated that the marginal mean cost difference between diabetic and non-diabetic patients was RMB (¥) 775.7.

Conclusions
AECOPD patients with comorbid diabetes had a more severe profile and higher direct hospitalization cost. Diabetes screening and integrated care programs might help reduce the heavy comorbidity and economic burden. Moreover, corticosteroids and metformin could be considered in the treatment of these patients.
Trial registration Clinicaltrials.gov with the identifier NCT0265752.
Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p
Authors: Li Junmin , Fan Rongmei , Xiao Hui 
Published: January 2021

Abstract
Background
A growing body of evidence has demonstrated the vital roles of circular RNAs (circRNAs) in cancer progression and drug resistance. We intended to explore the roles and mechanisms of circ_ZFR in the paclitaxel (PTX) resistance and progression of non-small cell lung cancer (NSCLC).

Methods
Two NSCLC cell lines A549 and H460 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to measure the levels of circ_ZFR, ZFR, miR-195-5p and karyopherin subunit alpha 4 (KPNA4) mRNA. RNase R assay was used to analyze the characteristic of circ_ZFR. MTT assay was carried out to assess PTX resistance and cell proliferation. Flow cytometry analysis was utilized to analyze cell cycle and apoptosis. Transwell assay was used to examine cell migration and invasion. Western blot assay was conducted to measure the protein levels of Ki67, Twist1, E-cadherin and KPNA4. Dual-luciferase reporter assay was adopted to verify the combination between miR-195-5p and circ_ZFR or KPNA4. Murine xenograft model assay was used to investigate the effect of circ_ZFR on PTX resistance of NSCLC in vivo.

Results
Circ_ZFR level was enhanced in PTX-resistant NSCLC tissues and cells. Knockdown of circ_ZFR suppressed PTX resistance, cell cycle process, proliferation, migration and invasion and induced apoptosis in PTX-resistant NSCLC cells. For mechanism analysis, circ_ZFR knockdown markedly downregulated the expression of KPNA4 by sponging miR-195-5p, thereby promoting PTX sensitivity and suppressing cell progression in PTX-resistant NSCLC cells. In addition, circ_ZFR silencing enhanced PTX sensitivity of NSCLC in vivo.

Conclusion
Circ_ZFR knockdown played a positive role in overcoming PTX resistance of NSCLC via regulating miR-195-5p/KPNA4 axis, which might provide a possible circRNA-targeted therapy for NSCLC.
Bacteria‐derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis‐associated cancer
Authors: Iwama Takuya , Fujiya Mikihiro , Konishi Hiroaki , Tanaka Hiroki , Murakami Yuki , Kunogi Takehito , Sasaki Takahiro , Takahashi Keitaro , Ando Katsuyoshi , Ueno Nobuhiro , Kashima Shin , Moriichi Kentaro , Tanabe Hiroki , Okumura Toshikatsu 
Published: January 2021

Abstract
Background
Colorectal cancers develop through several pathways, including the adenoma–carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.

Methods
SRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.

Results
Ferrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.

Conclusions
Ferrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.
Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting
Authors: Turner Triniti C. , Arama Charles , Ongoiba Aissata , Doumbo Safiatou , Doumtabé Didier , Kayentao Kassoum , Skinner Jeff , Li Shanping , Traore Boubacar , Crompton Peter D. , Götz Anton 
Published: January 2021

AbstractBackgroundPlasmodium falciparumcauses the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrentP. falciparuminfection on dendritic cell phenotype and function.MethodsIn this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected withP. falciparum(n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria.ResultsWith the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation withP. falciparumblood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.ConclusionsThe findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomaticP. falciparuminfections in malaria-endemic areas.
The effects of family physician-contracted service on health-related quality of life and equity in health in China
Authors: Lai Sha , Lu Li , Zhou Zhongliang , Shen Chi , Yang Xiaowei , Zhao Yaxin , Zhang Xiaolong 
Published: January 2021

Abstract
Background
Family physician-contracted service (FPCs) has been recently implemented in Chinese primary care settings. This study was aimed at measuring the effects of FPCs on residents’ health-related quality of life (HRQoL) and equity in health among the Chinese population.

Methods
The study data was drawn from the 2018 household health survey (Shaanxi Province, China) using multistage, stratified cluster random sampling. We measured HRQoL using EQ-5D-3L based on the Chinese-specific time trade-off values set. Coarsened exact matching (CEM) technique was used to control for confounding factors between residents with and without a contracted family physician. The concentration index (C) was calculated to measure equity in health.

Results
Individuals with a contracted family physician had significantly higher HRQoL than those without, after data matching (0.9355 vs. 0.8995; P <  0.001). Additionally, the inequity in HRQoL among respondents with a contracted family physician was significantly lower than those without a contracted family physician (Cs of EQ-5D utility score: 0.0084 vs. 0.0263; p <  0.001).

Conclusions
This study highlights the positive effects of FPCs on HRQoL and socioeconomic-related equity in HRQoL. Future efforts should prioritize the economically and educationally disadvantaged groups, the expansion of service coverage, and the competency of family physician teams to further enhance health outcome and equity in health.