bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory and microcosm experiments reveal contrasted adaptive responses to ammonia and water mineralisation in aquatic stages of the sibling species Anopheles gambiae s.s. and Anopheles coluzzii
Authors: Akpodiete Nwamaka Oluchukwu , Tripet Frederic 
Published: August 2020

Abstract
Background The sibling species of the malaria mosquito, Anopheles gambiae s.s and Anopheles coluzzii co-exist in many parts of West Africa and are thought to have recently diverged through a process of ecological speciation with gene flow. Divergent larval ecological adaptations, resulting in Genotype × Environment interactions have been proposed as important drivers of speciation in these species. In West Africa, An. coluzzii tends to be associated with permanent man-made larval habitats such as irrigated rice fields which are typically more eutrophic and mineral and ammonia-rich than the temporary rain pools exploited by An. gambiae s.s. Methods To highlight G×E interactions at the larval stage and their possible role in ecological speciation of these species, we first investigated the effect of exposure to ammonium hydroxide and water mineralisation on larval developmental success. Mosquito larvae were exposed to two water sources and increasing ammonia concentrations in small containers until adult emergence. In a second experiment, larval developmental success was compared across 2 contrasted microcosms to highlight G × E interactions under conditions like those found in the natural environment. Results The first experiment revealed significant G × E interactions in developmental success and phenotypic quality for both species in response to increasing ammonia concentrations and water mineralisation. The An. coluzzii strain outperformed the An. gambiae s.s. strain under limited conditions that were closer to more eutrophic habitats. The second experiment revealed divergent crisscrossing reaction norms in the developmental success of the sibling species in the two contrasted larval environments. As expected, An. coluzzii had higher emergence rates in the rice paddy environment with emerging adults of superior phenotypic quality compared to An. gambiae s.s, and vice versa in the rain puddle environment.Conclusions Evidence for such G x E interactions lends support to the hypothesis that divergent larval adaptations to the environmental conditions found in man-made habitats such as rice-fields in An. coluzzii may have been an important driver of its ecological speciation.
Regular Consumption of Soft Drinks is Associated with Type 2 Diabetes Incidence in Mexican Adults: Findings from a Prospective Cohort Study.
Authors: Torres-Ibarra Leticia , Rivera-Paredez Berenice , Hernández-López Rubí , Canto-Osorio Francisco , Sánchez-Romero Luz María , López-Olmedo Nancy , González Romina , Ramírez Paula , Salmerón Jorge , Barrientos-Gutiérrez Tonatiuh 
Published: August 2020

Abstract
Background: Although high consumption of soft drinks has been associated with excess of type 2 diabetes risk, the strength of this association in the Mexican population, where a type 2 diabetes genetic susceptibility has well established, has been scarcely studied. This study aimed to estimate the risk of type 2 diabetes due to soft drinks consumption in a cohort of Mexicans. Methods: We used data on 1,445 participants from the Health Workers Cohort Study, a prospective cohort conducted in Cuernavaca, Mexico. Soft drinks consumption was assessed with a semi-quantitative 116-item food frequency questionnaire. Incident type 2 diabetes was defined as self-report of physician-diagnosed type 2 diabetes, or fasting glucose >126 mg/dl, or use of hypoglycemic medication at any examination. Hazard ratios (HRs) along with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models.Results: With a total of 9,526.2 person-years of follow-up, 109 incident cases of type 2 diabetes were observed. Type 2 diabetes incidence rate was 7.6, 11.0, and 17.1 per 1,000 person-years across levels of soft drinks consumption of <1, 1-4, and ³5 servings/week, respectively (p<0.001 for trend). The intake of ≥5 soft drinks/week was significantly associated with an increased risk of type 2 diabetes (HR 2.0, 95%CI: 1.1–3.8) compared with consumption of <1/week. This association was not modified by family history of diabetes. The HR was attenuated by further adjustment for body mass index (HR 1.6, 95%CI: 0.8-2.9) and abdominal obesity (HR 1.7, 95%CI: 0.9-3.2). Conclusions: The consumption of soft drinks was associated with a higher risk of type 2 diabetes in a cohort of Mexican adults. Our results further support recommendations to limit intake of soft drinks to address the growing diabetes epidemic in Mexico.
Evaluation of Differential Peptide Loading on Tandem Mass Tag-Based Proteomic and Phosphoproteomic Data Quality
Authors: Sanford James A , Wang Yang , Hansen Joshua R , Gritsenko Marina A , Weitz Karl K , Tognon Cristina E , Petyuk Vladislav A , Qian Wei-Jun , Liu Tao , Druker Brian J , Rodland Karin D , Piehowski Paul D. 
Published: August 2020

Abstract
Background: Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One major barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics—currently on the order of 25 mg wet tissue weight, depending on tissue type. For hematopoietic cancers such as acute myeloid leukemia (AML), the sample requirement is in excess of 10 million (1E7) peripheral blood mononuclear cells (PBMCs). Throughout the course of a prospective study, this requirement will certainly exceed what is obtainable from many of the individual patients/timepoints. For this reason, we were interested in examining the impact of differential peptide loading across multiplex channels on proteomic data quality. Methods: To achieve this, we tested a range of channel loading amounts (20, 40, 100, 200, and 400 μg of tryptic peptides, or approximately the material obtainable from 5E5, 1E6, 2.5E6, 5E6, and 1E7 AML patient cells) to assess proteome coverage, quantification reproducibility and accuracy in experiments utilizing isobaric tandem mass tag (TMT) labeling. Results: As expected, we found that fewer missing values are observed in TMT channels with higher peptide loading amounts compared to those with lower loading. Moreover, channels with lower loading amounts have greater quantitative variability than channels with higher loading amounts. Statistical analysis of the differences in means among the five loading groups showed that the 20 μg loading group was significantly different from the 400 μg loading group. However, no significant differences were detected among the 40, 100, 200 and 400 μg loading groups. Conclusions: These assessment data demonstrate the practical limits of loading differential quantities of peptides across channels in TMT multiplexes, and provide a basis for designing the optimal clinical proteomics study when specimen quantities are limited.
A three-dimensional printed model in preoperative consent for ventricular septal defect repair
Authors: Deng Xicheng , He Siping , Huang Peng , Luo Jinwen , Yang Guangxian , Zhou Bing , Xiao Yunbin 
Published: August 2020

Abstract
Background: The 3D printing technology in congenital cardiac surgery has been widely utilized to improve patients’ understanding of their disease. However, there has been no randomized controlled study on its usefulness in surgical consent for congenital heart disease repair.Methods: A randomized controlled study was performed during consent process in which guardians of candidates for ventricular septal defect repair were given detailed explanation of the anatomy, indication for surgery and potential complication and risks using 3D print ventricular septal defect model (n = 20) versus a conventional 2D diagram (n = 20). A questionnaire was finished by each guardian of the patients. Data collected from questionnaires as well as medical records were statistically analyzed.Results: Statistically significant improvements in ratings of understanding of ventricular septal defect anatomy (p = 0.02), and of the course of procedure and potential complications (p = 0.02) were noted in the group that used the 3D model, though there was no difference in overall ratings of the consent process (p = 0.09). There was no difference in questionnaire score between subjects with different education level. The clinical outcomes, as represented by the duration of intensive care unit stay, intubation duration was comparable between the two groups.Conclusions: The results indicated that it was an effective tool which may be used to consent for congenital heart surgery. Different education levels do not affect guardians’ understanding in consent. The impact of 3D printing used in this scenario on long term outcomes remains to be defined.
Factorial Design Study of Total Petroleum Contaminated Soil Treatment Using Land Farming Technique
Authors: Okonofua Ehizonomhen Solomon , LASISI KAYODE HASSAN , Atikpo E 
Published: August 2020

Abstract
Land farming technique was used to treat hydrocarbon contaminated soil collected from a crude oil spill sites in Edo State, Nigeria. Calibrated standard auger was used to collect soil samples from the site at depth below 30 cm. The samples were characterized and classified. Cow dung and NPK fertilizer were added as additives to complement the nutriments of the soil samples before total petroleum hydrocarbon quantification and remediation procedures. Factorial design was applied to vary the input parameters such as pH, mass of substrate, moisture content and turning times of land farming so to ascertain the optimal conditions for the procedure. The result revealed that the in-situ TPH value was 5,000 mg/kg on the average and after 90 days of treatment, the turning rate, pH, moisture content and mass of substrate had 82.79%, 4.36%, 0.48% and 0.046% contributions respectively to land farming treatment. Numerical optimization techniques applied in the optimum point for land farming input parameters to achieve predicted maximum removal of 98.60% were evaluated as pH, mass of substrate, moisture content and turning rate to be 6.01, 1 kg, 10% and 5 times in a week respectively. TPH removed at this optimum point was 97.83% reducing from 5,000 mg/kg to 645.9 kg/mg. The high coefficient of determination (r2 = 0.9865) as observed in the closeness of predicted and experimental values reflects the reliability of the model and hence, land farming practice with close attention on turning rate as revealed by this study, is recommended for TPH contaminated soil remediation.
Exosomes Derived from miR-301a-3p-Modified Adipose-derived Mesenchymal Stem Cells Reverse Hypoxia-induced Erectile Dysfunction in Rat Models
Authors: Liang Li , Zheng Dachao , Lu Chao , Xi Qinghong , Bao Hua , Li Wengfeng , Gu Yufei , Mao Yuanshen , Xu Bin , Gu Xin 
Published: August 2020

Abstract
Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived stem cells (ADSCs)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED. In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs). Results showed that miR-301a-3p-enriched exosomes treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha Smooth Muscle Actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that Phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p. Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/HIF-1α and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered as a new therapeutic target for treating ED associated with OSA.
Molecular Remission at T cell level in Patients with Rheumatoid Arthritis
Authors: Inamo Jun , Suzuki Katsuya , Takeshita Masaru , Kondo Yasushi , Okuzono Yuumi , Koga Keiko , Kassai Yoshiaki , Takiguchi Maiko , Kurisu Rina , Morita Rimpei , Yoshimura Akihiko , Takeuchi Tsutomu 
Published: August 2020

Abstract
Background: While numerous disease-modifying anti-rheumatic drugs (DMARDs) has brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain such as small proportion of achievement drug-free patients. The aim of this study is to explore key molecules for remission at T cell level, which is known to involve the pathogenesis of RA deeply, and investigate disease course of patients who achieved molecular remission (MR). Methods: We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4 + T cells and CD8 + T cells of patients with RA using machine learning methods. In addition, we investigated the benefit of achieving MR on disease control thereafter. Results: We identified 9 and 23 genes that were associated with clinical remission in CD4 + and CD8 + T cells. Principal component analysis (PCA) demonstrated expression profiling of them was similar with HCs. As to remission signature genes in CD4 + T cells, PCA result was reproduced using validation cohort, indicating their robustness. There was a trend towards better disease control during 12 months follow-up in patients treated with tocilizumab in deep MR than those in non-deep MR, although it was not significant. Conclusion: We identified robust genes which represented remission status in CD4 + T cells using machine learning techniques. The current study will promote our understandings about molecular mechanism to achieve deep remission in the management of RA.Trial registration: Not required.
C deletion of the SLC39A8 gene polymorphism (rs74650330) increases the risk of coronary artery disease in individuals with low LDL cholesterol levels
Authors: Zhang Jun , Yu Yang , Pan Lili , Yu Tianhong , Luo Guanghua 
Published: August 2020

Abstract
Background: The genetic variant of SLC39A8 is associated with several cardiovascular disease risk factors, including body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-density lipoprotein cholesterol (HDL-C) levels. The present study aimed to investigate the association between the SLC39A8 SNPs rs13107325 and rs74650330 and CAD in the Han population in Jiangsu (China).Methods: Genotyping of these SNPs was performed in 258 patients with CAD and 170 healthy controls using the base-quenched probe technique. The association between rs74650330 and blood lipid and glucose profiles was investigated.Results: The rs13107325 polymorphism was not found in the 428 Chinese individuals enrolled in the current study. For rs74650330, individuals harboring the C allele had significantly higher HDL levels than those without this allele in the control group (P=0.039), while the opposite was true for LDL-C levels (P=0.046). Further analysis indicated that when LDL-C levels were lower than 2.365 mmol/L, subjects with C/del and del/del had a 7.293-fold increased risk of CAD compared with that of controls without the mutation (odds ratio: 7.293; 95% confidence interval: 0.953-55.79).Conclusions: The results obtained in the current study suggested that the rs74650330 polymorphism is associated with reduced HDL-C and elevated LDL-C levels in healthy individuals. When LDL-C levels were lower than 2.365 mmol/L, the C/del genotype significantly increased the risk of CAD in the Chinese Han population.
Generation of induced tumor-suppressing cells from osteoblasts and mesenchymal stem cells
Authors: Sun Xun , Zha Rongrong , Li Kexin , Liu Shengzhi , Fan Yao , Wu Di , Hase Misato , Robling Alexander , Li Bai-Yan , Yokota Hiroki 
Published: August 2020

Abstract
Background

The current treatment for breast cancer-associated bone metastasis is palliative, and there is an unmet need to develop an effective regimen. In this study, we examined the possibility of conditioned medium (CM)-based therapy with bone-forming osteoblasts and their precursors, mesenchymal stem cells (MSCs).
Methods

Tumor cell lines, human breast cancer tissues, and a mouse model of mammary tumors and bone metastasis were employed to examine the tumor-suppressing effect of osteoblast- and MSC-derived CM. Tumor-driven osteolysis was evaluated using micro CT imaging and histology, and tumorigenic signaling was analyzed with an antibody-based protein array and Western blotting in response to the overexpression and RNA silencing of the key regulatory factors.
Results

Osteoblast- and MSC-derived CM without any overexpression did not alter the progression of mammary tumor cells. However, overexpressing Lrp5 and Snail converted them into induced tumor-suppressing (iTS) cells. In the mouse model, the systemic administration of iTS cell-derived CM reduced the weight of mammary tumors and suppressed tumor-induced osteolysis. The same outcome was observed with the overexpression of p53, a tumor-suppressing gene. In Lrp5-overexpressing CM, cytokines such as CXCL2 and LIF were downregulated, while p53 and Trail, an apoptosis-inducing factor, were upregulated. The overexpression of p53 in MSCs also reduced CXCL2 and LIF with an elevation of Trail. Notably, iTS cells were generated from mammary tumor cells by the overexpression of Lrp5 or Snail. We postulate that natural selection via cell competitions might be involved in the anti-tumor capability of iTS cells against tumor cells.
Conclusions

This study demonstrates that osteoblasts and MSCs can be converted into iTS cells by overexpressing the selected genes, and p53 is involved in the action of iTS cells. An iTS CM-based therapy may provide a novel option to treat primary and metastatic breast cancers.
PDIA3 Reduce Glioma-associated Macrophage/microglia Pro-tumor Activation trough IL-6-STAT3-PDIA3 Pathway.
Authors: Chiavari Marta , Ciotti Gabriella Maria Pia , Canonico Francesco , Altieri Fabio , Navarra Pierluigi , Lisi Lucia 
Published: August 2020

Abstract
Background: Glioblastoma (GB - grade IV glioma) is the most aggressive and common cancer of central nervous system with an overall survival of 14-16 months. The GB tumor microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs). It is known that between GAMs and GB cells there is a double interaction, but the role of GAMs is still poorly characterized. The endoplasmic reticulum (ER) protein ERp57, also known as PDIA3, is a thiol oxidoreductase with main function related on glycoprotein folding in endoplasmic reticulum. However, PDIA3 shows different functions. In fact, the various subcellular localizations and binding partners of PDIA3 affect numerous physiological processes and diseases: different regulation and modulation of PDIA3 has been reported in multiple pathologies including neurodegenerative diseases and cancer. Methods: In the present work, we evaluated in both GB cells and microglia-macrophage cells the expression of PDIA3 using specimens collected after surgical from 18 GB patients. In addition, we studied in vitro microglia-glioma interaction to determine the role of PDIA3 in viability and the activation of both GB and microglia cells. The study was carried using PDIA3-silenced T98G cells and/or using a pharmacological inhibitor of PDIA3 activity (Punicalagin-PUN).Results: We initially investigated the role of the PDIA3 in GB survival by inquiring The Cancer Genome Atlas dataset. The results indicated that 352 out of 690 patients reported over-expression of PDIA3, which significantly correlated with a ~55% reduction of overall survival. Subsequently, for the first time, we investigated the PDIA3 expression in the tumor and the nearby parenchyma of 18 GB patients and our data showed a significant upregulation (15% vs 10%) of ERp57/PDIA3 in GAMs of tumor specimens respect the microglia present in parenchyma. In addition, we show that conditioned medium (CMs) obtained from both wild type T98G and PDIA3 silenced T98G induced an activation of microglia cells, but the PDIA3 silenced-T98G CMs significant limited the microglia pro-tumor activation probably through a IL-6-STAT3-PDIA3 dependent mechanism. Conclusion: Our data support the relevant role of PDIA3 expression in GB pathology and link the different activation of microglia to a mechanism a IL-6-STAT3-PDIA3 dependent.
CXCL11 Correlates with Anti-tumor Immune Microenvironment and Improved Prognosis in Colon Cancer
Authors: Cao Yingying , Zhang Youwei , Jiao Nanlin , Sun Tiantian , Ma Yanru , Zhang Xinyu , Hong Jie , CHEN HAOYAN 
Published: August 2020

Abstract
Background: CXCL11 has been considered to be responsible for tumor development, but the specific effect of CXCL11 in colon cancer was still obscure. Therefore, the prognostic value and immunological regulation effect of CXCL11 in colon cancer were evaluated in this study.Methods: Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n=451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, the patient cohort (the Yijishan Hospital cohort, YJSHC, n=108) was utilized for cell infiltration-related analysis, accordingly. Both CXCL11 mRNA expression and CXCL11+ (CXCL11-producing) cells were assessed in colon cancer, whose effect on prognosis and immunological regulation was also studied. Results: High CXCL11 expression were associated with better prognosis in colon cancer, which was still significant even if clinicopathological factors were adjusted. Furthermore, CXCL11 positively correlated with anti-tumor cells infiltration, such as CD8+ T cells and natural killer cells. Meanwhile, CXCL11 correlated positively with several genes associated with DC, NK and T recruitment，and a gene set of cytotoxic genes. Notably, CXCL11 correlated positively with several immune checkpoint related genes including of PD-L1. Conclusions: CXCL11 contributed to anti-tumor immune microenvironment and could improve prognosis in patients with colon cancer. Especially, it’s a potential approach that inducible expression of CXCL11 by genetic and pharmacological interventions is able to improve prognosis and response to anti-PD-1 (programmed cell death protein-1) antibody treatment in colon cancer. However, it requires to be verified by further prospective investigations.