bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression kinetics of Exaiptasia pallida innate immune response to Vibrio parahaemolyticus infection
Authors: Seneca François , Davtian David , Boyer Laurent , Czerucka Dorota 
Published: November 2020

Abstract

Background
Recent sequencing projects on early-diverging metazoans such as cnidarians, have unveiled a rich innate immunity gene repertoire; however, little is known about immunity gene regulation in the host’s early response against marine bacterial pathogens over time. Here, we used RNA-seq on the sea anemone Exaiptasia pallida (Ep) strain CC7 as a model to depict the innate immune response during the onset of infection with the marine pathogenic bacteria Vibrio parahaemolyticus (Vp) clinical strain O3:K6, and lipopolysaccharides (LPS) exposure. Pairwise and time series analyses identified the genes responsive to infection as well as the kinetics of innate immune genes over time. Comparisons between the responses to live Vp and purified LPS was then performed.

Results
Gene expression and functional analyses detected hundreds to thousands of genes responsive to the Vp infection after 1, 3, 6 and 12 h, including a few shared with the response to LPS. Our results bring to light the first indications that non-canonical cytoplasmic pattern recognition receptors (PRRs) such as NOD-like and RIG-I-like receptor homologs take part in the immune response of Ep. Over-expression of several members of the lectin-complement pathways in parallel with novel transmembrane and Ig containing ficolins (CniFLs) suggest an active defense against the pathogen. Although lacking typical Toll-like receptors (TLRs), Ep activates a TLR-like pathway including the up-regulation of MyD88, TRAF6, NF-κB and AP-1 genes, which are not induced under LPS treatment and therefore suggest an alternative ligand-to-PRR trigger. Two cytokine-dependent pathways involving Tumor necrosis factor receptors (TNFRs) and several other potential downstream signaling genes likely lead to inflammation and/or apoptosis. Finally, both the extrinsic and intrinsic apoptotic pathways were strongly supported by over-expression of effector and executioner genes.

Conclusions
To our knowledge, this pioneering study is first to follow the kinetics of the innate immune response in a cnidarian during the onset of infection with a bacterial pathogen. Overall, our findings reveal the involvement of both novel immune gene candidates such as NLRs, RLRs and CniFLs, and previously identified TLR-like and apoptotic pathways in anthozoan innate immunity with a large amount of transcript-level evidence.
Skin pigmentation polymorphisms associated with increased risk of melanoma in a case-control sample from southern Brazil
Authors: Reis Larissa B. , Bakos Renato M. , Vianna Fernanda S. L. , Macedo Gabriel S. , Jacovas Vanessa C. , Ribeiro-dos-Santos André M. , Santos Sidney , Bakos Lúcio , Ashton-Prolla Patricia 
Published: November 2020

Abstract

Background
Melanoma is the most aggressive type of skin cancer and is associated with environmental and genetic risk factors. It originates in melanocytes, the pigment-producing cells. Single nucleotide polymorphisms (SNPs) in pigmentation genes have been described in melanoma risk modulation, but knowledge in the field is still limited.

Methods
In a case-control approach (107 cases and 119 controls), we investigated the effect of four pigmentation gene SNPs (TYR rs1126809, HERC2 rs1129038, SLC24A5 rs1426654, and SLC45A2 rs16891982) on melanoma risk in individuals from southern Brazil using a multivariate logistic regression model and multifactor dimensionality reduction (MDR) analysis.

Results
Two SNPs were associated with an increased risk of melanoma in a dominant model: rs1129038AA and rs1426654AA [OR = 2.094 (95% CI: 1.106–3.966), P = 2.3 10− 2 and OR = 7.126 (95% CI: 1.873–27.110), P = 4.0 10− 3, respectively]. SNP rs16891982CC was associated with a lower risk to melanoma development in a log-additive model when the allele C was inherited [OR = 0.081 (95% CI: 0.008–0.782), P = 3 10− 2]. In addition, MDR analysis showed that the combination of the rs1426654AA and rs16891982GG genotypes was associated with a higher risk for melanoma (P = 3 10− 3), with a redundant effect.

Conclusions
These results contribute to the current knowledge and indicate that epistatic interaction of these SNPs, with an additive or correlational effect, may be involved in modulating the risk of melanoma in individuals from a geographic region with a high incidence of the disease.
Establishment of an immune-related gene pair model to predict colon adenocarcinoma prognosis
Authors: Luo Jihang , Liu Puyu , Wang Leibo , Huang Yi , Wang Yuanyan , Geng Wenjing , Chen Duo , Bai Yuju , Yang Ze 
Published: November 2020

Abstract

Background
Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD.

Methods
The gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis.

Results
Among 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P<0.001). Univariate and multivariate Cox proportional hazard analyses confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways were upregulated in the high-risk groups. Regulatory T cells and macrophages M0 were significantly highly expressed in the high-risk group.

Conclusion
We successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.
Network governance forms in healthcare: empirical evidence from two Italian cancer networks
Authors: Romiti Anna , Del Vecchio Mario , Sartor Gino 
Published: November 2020

AbstractBackgroundThis study focuses on the application of Provan and Kenis’ modes of network governance to the specific field of public healthcare networks, extending the framework to an analysis of systems in which networks are involved. Thus, the aim of this study is to analyze and compare the governance of two cancer networks in two Italian regions that underwent system reconfiguration processes due to reforms in the healthcare system.MethodsA qualitative study of two clinical networks in the Italian healthcare system was conducted. The sample for interviews included representatives of the regional administration (n = 4), network coordinators (n = 6), and general and clinical directors of health organizations involved in the two networks (n = 25). Data were collected using semi-structured interviews.ResultsOur study shows that healthcare system reforms have a limited impact on network governance structures. In fact, strong inertial tendencies characterize networks, especially network administrative organization models (NAO). Networks tend to find their own balance with respect to the trade-offs analyzed using a mix of formal and informal ties. Our study confirms the general validity of Provan and Kenis’ framework and shows how other specific factors and contingencies may affect the possibility that cancer networks find positive equilibria between competing needs of inclusivity and efficiency, internal and external legitimacy, and stability and flexibility. It also shows how networks react to external changes.ConclusionsOur study shows the importance of considering three factors and contingencies that may affect network effectiveness: a) the importance of looking at network governance modes not in isolation, but in relationship to the governance of regional systems; b) the influence of a specific network’s governance structure on the network’s ability to respond to tensions and to achieve its goals; and c) the need to take into account the role of professionals in network governance.
ZBTB7A, a potential biomarker for prognosis and immune infiltrates, inhibits progression of endometrial cancer based on bioinformatics analysis and experiments
Authors: Geng Rong , Zheng Yuhua , zhou Donghua , Li Qingdong , Li Ruiman , Guo Xiaoling 
Published: November 2020

Abstract

Backgroud
ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. The ZBTB7A has been largely linked to different kinds of tumors due to its diverse function. However, the value for ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear.

Methods
In our work, we assessed the importance of ZBTB7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co-expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZBTB7A and tumor immune invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CCK8, migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrial cancer cells.

Results
We found the ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expression of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers such as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Treg. Finally, we verified that ZBTB7A repressed E2F4 transcription and inhibited cells proliferation and migration. These results indicate that ZBTB7A may play a vital role in regulating immune cell infiltration in UCEC, and is a valuable prognostic marker.

Conclusions
In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, plays a vital role in regulating immune cell infiltration, possesses diagnostic and prognostic values and attenuates E2F4 transcription and cell proliferation, migration in vitro.
Climate factors and gestational diabetes mellitus risk – a systematic review
Authors: Preston Emma V. , Eberle Claudia , Brown Florence M. , James-Todd Tamarra 
Published: November 2020

AbstractBackgroundCurrent and projected increases in global temperatures and extreme climate events have led to heightened interest in the impact of climate factors (i.e. ambient temperature, season/seasonality, and humidity) on human health. There is growing evidence that climate factors may impact metabolic function, including insulin sensitivity. Gestational diabetes mellitus (GDM) is a common pregnancy complication, with an estimated global prevalence of up to 14%. While lifestyle and genetic risk factors for GDM are well established, environmental factors may also contribute to GDM risk. Previous reviews have summarized the growing evidence of environmental risk factors for GDM including endocrine disrupting chemicals and ambient air pollution. However, studies of the effects of climate factors on GDM risk have not been systematically evaluated. Therefore, we conducted a systematic review to summarize and evaluate the current literature on the associations of climate factors with GDM risk.MethodsWe conducted systematic searches in PubMed and EMBASE databases for original research articles on associations of climate factors (i.e. ambient temperature, season/seasonality, and humidity) with GDM and/or related glycemic outcomes for all publication dates through September 20th, 2020.ResultsOur search identified 16 articles on the associations of ambient temperature and/or season with GDM and maternal glycemic outcomes during pregnancy, which were included in this review. Despite inconsistencies in exposure and outcome assessment, we found consistent evidence of a seasonal effect on GDM risk, with higher prevalence of GDM and higher pregnancy glucose levels in summer months. We found suggestive evidence of an association between higher ambient temperature and elevated glucose levels from GDM screening tests.ConclusionClimate factors may be associated with GDM risk. However, further research is needed to evaluate these associations and to elucidate the specific mechanisms involved.
Measuring the association of objective and perceived neighborhood environment with physical activity in older adults: challenges and implications from a systematic review
Authors: Peters Manuela , Muellmann Saskia , Christianson Lara , Stalling Imke , Bammann Karin , Drell Carina , Forberger Sarah 
Published: November 2020

AbstractBackgroundA supportive environment is a key factor in addressing the issue of health among older adults. There is already sufficient evidence that objective and self-reported measures of the neighborhood environment should be taken into account as crucial components of active aging, as they have been shown to influence physical activity; particularly in people aged 60+. Thus, both could inform policies and practices that promote successful aging in place. An increasing number of studies meanwhile consider these exposures in analyzing their impact on physical activity in the elderly. However, there is a wide variety of definitions, measurements and methodological approaches, which complicates the process of obtaining comparable estimates of the effects and pooled results. The aim of this review was to identify and summarize these differences in order to emphasize methodological implications for future reviews and meta analyzes in this field and, thus, to create a sound basis for synthesized evidence.MethodsA systematic literature search across eight databases was conducted to identify peer-reviewed articles examining the association of objective and perceived measures of the neighborhood environment and objectively measured or self-reported physical activity in adults aged ≥ 60 years. Two authors independently screened the articles according to predefined eligibility criteria, extracted data, and assessed study quality. A qualitative synthesis of the findings is provided.ResultsOf the 2967 records retrieved, 35 studies met the inclusion criteria. Five categories of methodological approaches, numerous measurement instruments to assess the neighborhood environment and physical activity, as well as several clusters of definitions of neighborhood, were identified.ConclusionsThe strength of evidence of the associations of specific categories of environmental attributes with physical activity varies across measurement types of the outcome and exposures as well as the physical activity domain observed and the operationalization of neighborhood. The latter being of great importance for the targeted age group. In the light of this, future reviews should consider these variations and stratify their summaries according to the different approaches, measures and definitions. Further, underlying mechanisms should be explored.
Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy
Authors: Ma Ke , Zhu Bo , Wang Zetao , Cai Peian , He Mingwei , Ye Danyan , Yan Guohua , Zheng Li , Yang Lujun , Zhao Jinmin 
Published: November 2020

Abstract

Background
Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported.

Results
We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy.

Conclusions
C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.
Intracholecystic papillary neoplasm arising in a patient with pancreaticobiliary maljunction: a case report
Authors: Iwasaki Toshimitsu , Otsuka Yasuhiro , Miyata Yoichi , Einama Takahiro , Tsujimoto Hironori , Ueno Hideki , Ogata Sho , Kishi Yoji 
Published: November 2020

AbstractBackgroundPancreaticobiliary maljunction (PBM) is a congenital abnormality in which the pancreatic and biliary ducts join anatomically outside the duodenal wall resulting in the regurgitation of pancreatic juice into the biliary tract (pancreatobiliary reflux). Persistent pancreatobiliary reflux causes injury to the epithelium of the biliary tract and promotes the risk of biliary cancer. Intracholecyctic papillary neoplasm (ICPN) has been highlighted in the context of a cholecystic counterpart of intraductal papillary mucinous neoplasm of the pancreas and the bile duct, but the tumorigenesis of ICPNs remains unclear.Case presentationA 52-year-old Japanese woman was referred for the assessment of dilation of the bile duct. Computed tomography which revealed an enhanced mass in the gallbladder and endoscopic retrograde cholangiopancreatography confirmed that the confluence of the main pancreatic duct and extrahepatic bile duct (EHBD) was located outside the duodenal wall. Under the diagnosis of gallbladder cancer with PBM, cholecystectomy with full thickness dissection, EHBD resection, lymph node dissection, and hepaticojejunostomy were performed. Macroscopic examination of the resected specimen showed that the cystic duct was dilated and joined into the EHBD just above its confluence with the pancreatic duct, and the inflamed change of non-tumorous mucosa of gallbladder indicating that there was considerable mucosal injury due to pancreatobiliary reflux to the gallbladder. Histopathological examination revealed that the gallbladder tumor was a gastric-type ICPN with non-invasive component. EitherKRASgene mutation or p53 protein expression that were known to be associated with the carcinogenesis of biliary cancer under the condition of pancreatobiliary reflux was not detected in the tumor cells of ICPN.ConclusionThe present case might suggest that there was no association between PBM and ICPN. To reveal the tumorigenesis of ICPN and its attribution to pancreatobiliary reflux, however, further study is warranted.
Frequent use of emergency departments and chronic conditions in ageing societies: a retrospective analysis based in Italy
Authors: di Bella Enrico , Gandullia Luca , Leporatti Lucia , Locatelli Walter , Montefiori Marcello , Persico Luca , Zanetti Roberta 
Published: November 2020

AbstractBackgroundMost western countries are facing relevant demographic changes, and the percentage of older people is destined to rise in the next decades. This fact is likely to affect the sustainability of healthcare systems significantly, mainly due to the connected issue of chronicity.MethodsIn this paper, using an extensive and comprehensive administrative dataset, we analyse the phenomenon of frequent use of emergency departments (ED) in the oldest region in Europe (i.e. Liguria) over 4 years (2013–2016). Two alternative approaches are used to define categories of ED users based on the intensity and frequency of accesses and splitting patients into different age groups.ResultsResults allow identifying clinical and socio-demographic risk-factors connected to different levels of ED utilisation and highlight the influential role played by chronic conditions (particularly mental disorders, respiratory diseases) and by multiple chronic conditions.ConclusionsThe study aims at representing an informative tool to support policy-makers in setting proper policies addressed, on the one side, towards the potentially preventable frequent users and, on the other, towards those accessing due to complex medical conditions. The results can help in building a warning system to help general practitioners in the identification of potential frequent users and to develop preventive policies.
Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study
Authors: Kesse-Guyot Emmanuelle , Rebouillat Pauline , Payrastre Laurence , Allès Benjamin , Fezeu Léopold K. , Druesne-Pecollo Nathalie , Srour Bernard , Bao Wei , Touvier Mathilde , Galan Pilar , Hercberg Serge , Lairon Denis , Baudry Julia 
Published: November 2020

AbstractBackgroundOrganic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors.The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D.MethodsA total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014–2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors).ResultsDuring follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43–0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95–0.99).ConclusionsIn this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations.Clinical trial registryThe study was registered at ClinicalTrials.gov (NCT03335644).