bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma
Authors: Otoukesh Babak , Abbasi Mehdi , Gorgani Habib-o-Lah , Farahini Hossein , Moghtadaei Mehdi , Boddouhi Bahram , Kaghazian Peyman , Hosseinzadeh Shayan , Alaee Atefe 
Published: June 2020

AbstractMicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.
Relationship between different particle size fractions and all-cause and cause-specific emergency ambulance dispatches
Authors: Wang Xiaojie , Tian Junzhang , Li Ziyi , Lai Jun , Huang Xin , He Yongcong , Ye Zebing , Li Guowei 
Published: June 2020

Abstract
Background
Evidence on the relationship between different particle size fractions and emergency ambulance dispatches (EAD) remains limited and sparse.

Methods
We collected daily data of EAD, ambient air pollution and meteorological data from 2014 to 2018 in Guangzhou, China. We used a generalized additive model with covariate adjustments to estimate the associations between different particle size fractions and EAD related to all-cause, cardiovascular diseases, and respiratory diseases. Several subgroup and sensitivity analyses were also performed.

Results
Significant associations were observed between PM2.5, PM2.5–10, PM10 and EADs. A 10 μg/m3 increase of PM2.5, PM2.5–10, and PM10 was associated with an increase of 0.98% (95% CI: 0.67, 1.28%), 2.06% (95% CI: 1.44, 2.68%), and 0.75% (95%CI: 0.53, 0.96%) in all-cause EAD, with an increase of 0.69% (95% CI: 0.00, 1.39%), 2.04% (95% CI: 0.64, 3.45%), and 0.60% (95%CI: 0.11,1.10%) in cardiovascular-related EAD, and an increase of 1.14% (95% CI: 0.25, 2.04%), 2.52% (95% CI: 0.72, 4.35%), and 0.89% (95%CI: 0.25,1.52%) in respiratory-related EAD at lag03, respectively. The results were robust in subgroup and sensitivity analyses.

Conclusions
This study revealed that PM2.5, PM2.5–10 and PM10 were significantly related with risks of all-cause and cause-specific EAD. More evidence of high quality may be needed to further support our results in this ecological study.
Impacts of ambient air pollution on glucose metabolism in Korean adults: a Korea National Health and Nutrition Examination Survey study
Authors: Hwang Myung-Jae , Kim Jong-Hun , Koo Youn-Seo , Yun Hui-Young , Cheong Hae-Kwan 
Published: June 2020

Abstract
Background
Exposure to air pollution was reported to affect glucose metabolism, increasing the risk of diabetes mellitus. We conducted an epidemiological study on glucose metabolism and air pollution by exploring the levels of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with changes in ambient air quality, depending on the characteristics of the susceptible population.

Methods
We carried out a cross-sectional analysis of a nationally representative sample of 10,014 adults (4267 in male and 5747 in female) from the Korea National Health and Nutrition Examination Survey in 2012 and 2013 along with data from the Korean Air Quality Forecasting System. The analysis was performed using a generalized linear model stratified by sex, age, and presence of diabetes. We assessed the changes in FBG and HbA1c associated with exposures to particulate matter (PM10), fine particulate matter (PM2.5), and nitrogen dioxide (NO2) after controlling for confounders.

Results
There were 1110 participants with diabetes (557 in male and 553 in female). Overall, the FBG level increased by 7.83 mg/dL (95% confidence interval [CI]: 2.80–12.87) per interquartile range (IQR) increment of NO2, 5.32 mg/dL (95% CI: 1.22–9.41) per IQR increment of PM10 at a moving average of 0–6 days, and 4.69 mg/dL (95% CI: 0.48–8.91) per IQR increment of PM2.5 at a moving average of 0–5 days. HbA1c increased by 0.57% (95% CI: 0.04–1.09) per IQR increment of PM10 at a moving average of 0–60 days and 0.34% (95% CI: 0.04–0.63) per IQR increment of PM2.5 at a moving average of 0–75 days. The change in FBG and HbA1c increased more in the diabetic group, especially in males aged 65 years or more. There was a strong association between elevation in diabetes-related parameters and exposure to air pollution.

Conclusions
Our study provides scientific evidence supporting that short- and mid-term exposure to air pollution is associated with changes in biological markers related to diabetes. This finding suggests that the impact of air pollution should be reflected in chronic disease management when establishing local health care policies.
Occupational pesticide exposure and the risk of death in patients with Parkinson’s disease: an observational study in southern Brazil
Authors: Schneider Medeiros Márcio , P. Reddy Sumanth , P. Socal Mariana , Schumacher-Schuh Artur Francisco , Mello Rieder Carlos Roberto 
Published: June 2020

AbstractBackgroundMultiple studies have suggested that various pesticides are associated with a higher risk of developing Parkinson’s disease (PD) and may influence the progression of the disease. However, the evidence regarding the impact of pesticide exposure on mortality among patients with PD is equivocal. This study examines whether pesticide exposure influences the risk of mortality among patients with PD in Southern Brazil.MethodsA total of 150 patients with idiopathic PD were enrolled from 2008 to 2013 and followed until 2019. In addition to undergoing a detailed neurologic evaluation, patients completed surveys regarding socioeconomic status and environmental exposures.ResultsTwenty patients (13.3%) reported a history of occupational pesticide exposure with a median duration of exposure of 10 years (mean = 13.1, SD = 11.2). Patients with a history of occupational pesticide exposure had higher UPDRS-III scores, though there were no significant differences in regards to age, sex, disease duration, Charlson Comorbidity Index, and age at symptom onset. Patients with occupational pesticide exposure were more than twice as likely to die than their unexposed PD counterparts (HR = 2.32, 95% CI [1.15, 4.66],p = 0.018). Occupational pesticide exposure was also a significant predictor of death in a cox-proportional hazards model which included smoking and caffeine intake history (HR = 2.23, 95% CI [1.09, 4.59],p = 0.03)) and another which included several measures of socioeconomic status (HR = 3.91, 95% CI [1.32, 11.58],p = 0.01).ConclusionIn this prospective cohort study, we found an increased all-cause mortality risk in PD patients with occupational exposure to pesticides. More studies are needed to further analyze this topic with longer follow-up periods, more detailed exposure information, and more specific causes of mortality.
Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis
Authors: Ma Li , Qiang Junhao , Yin Heliang , Lin Lin , Jiao Yan , Ma Changying , Li Xinwei , Dong Li , Cui Jinglin , Wei Dongmei , Sharma Ankur M. , Schwartz David L. , Gu Weikuan , Chen Hong 
Published: June 2020

Abstract
Background
Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT.

Methods
We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS.

Results
The median follow-up of patients was 20.5 months (range, 6.1–38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively.

Conclusion
Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.
Identification of a novel IL-5 signaling pathway in chronic pancreatitis and crosstalk with pancreatic tumor cells
Authors: Gitto Sarah B. , Beardsley Jordan M. , Nakkina Sai Preethi , Oyer Jeremiah L. , Cline Kathryn A. , Litherland Sally A. , Copik Alicja J. , Khaled Amr S. , Fanaian Na’im , Arnoletti J. Pablo , Altomare Deborah A. 
Published: June 2020

Abstract
Background
While inflammation is associated with pancreatic cancer, the underlying mechanisms leading to cancer initiation are still being delineated. Eosinophils may promote or inhibit tumor growth, although the specific role in pancreatic cancer has yet to be determined. Eosinophil-supporting cytokine interleukin-5 and receptor are likely to have a role, but the significance in the pancreatic cancer microenvironment is unknown.

Methods
Genetically engineered Akt1Myr/KRasG12D and KRasG12D mice were used to model changes induced by chronic inflammation. Tissue samples were collected to analyze the tumor microenvironment and infiltration of immune cells, whereas serum was collected to analyze cytokine and amylase activity in the inflammatory model. The expression of IL-5R and the effects of IL-5 were analyzed in human and murine tumor cells.

Results
Compound Akt1Myr/KRasG12D mice, compared to single KRasG12D or Akt1Myr mice, exhibited increased tissue damage after repeat inductions of inflammation, and had accelerated tumor development and metastasis. M2 macrophages and newly identified eosinophils co-localized with fibrotic regions rather than infiltrating into tumors, consistent with immune cell privilege. The majority of eosinophils found in the pancreas of Akt1Myr/KRasG12D mice with chronic inflammation lacked the cytotoxic NKG2D marker. IL-5 expression was upregulated in pancreatic cells in response to inflammation, and then diminished in advanced lesions. Although not previously described in pancreatic tumors, IL-5Rα was increased during mouse pancreatic tumor progression and expressed in human pancreatic ductal adenocarcinomas (7 of 7 by immunohistochemistry). IL-5 stimulated tumor cell migration and activation through STAT5 signaling, thereby suggesting an unreported tumor-promoting role for IL-5Rα in pancreatic cancer.

Conclusions
Chronic inflammation induces increased pancreatic cancer progression and immune cells such as eosinophils are attracted to areas of fibrosis. Results suggest that IL-5 in the pancreatic compartment stimulates increased IL-5Rα on ductal tumor cells to increase pancreatic tumor motility. Collectively, IL-5/IL-5Rα signaling in the mouse and human pancreatic tumors microenvironment is a novel mechanism to facilitate tumor progression.
Evaluation of T-activated proteins as recall antigens to monitor Epstein–Barr virus and human cytomegalovirus-specific T cells in a clinical trial setting
Authors: Körber Nina , Behrends Uta , Protzer Ulrike , Bauer Tanja 
Published: June 2020

Abstract
Background
Pools of overlapping synthetic peptides are routinely used for ex vivo monitoring of antigen-specific T-cell responses. However, it is rather unlikely that these peptides match those resulting from naturally processed antigens. T-activated proteins have been described as immunogenic and more natural stimulants, since they have to pass through antigen processing and comprise activation of all clinically relevant effector cell populations.

Methods
We performed comparative analysis of numbers and cytokine expression pattern of CD4 and CD8 T cells after stimulation with recombinant, urea-formulated T-activated EBV-BZLF1, -EBNA3A, and HCMV-IE1, and -pp65 proteins or corresponding overlapping peptide pools. Freshly isolated and cryopreserved PBMC of 30 EBV- and 19 HCMV-seropositive and seven EBV- and HCMV-seronegative subjects were stimulated ex vivo and analysed for IFN-γ, TNF and IL-2 production by flow cytometry-based intracellular cytokine staining.

Results
T-activated proteins showed a high specificity of 100% (EBV-BZLF1, HCMV-IE1, and -pp65) and 86% (EBV-EBNA3A), and a high T-cell stimulatory capacity of 73–95% and 67–95% using freshly isolated and cryopreserved PBMC, respectively. The overall CD4 T-cell response rates in both cohorts were comparable after stimulation with either T-activated protein or peptide pools with the exception of lower numbers of CD8 T cells detected after stimulation with T-activated EBV-EBNA3A- (p = 0.038) and HCMV-pp65- (p = 0.0006). Overall, the number of detectable antigen-specific T cells varied strongly between individuals. Cytokine expression patterns in response to T-activated protein and peptide pool-based stimulation were similar for CD4, but significantly different for CD8 T-cell responses.

Conclusion
EBV and HCMV-derived T-activated proteins represent innovative, highly specific recall antigens suitable for use in immunological endpoint assays to evaluate success or failure in immunotherapy clinical trials (e.g. to assess the risk of EBV and/or HCMV reactivation after allogenic hematopoietic stem cell transplantation). T-activated proteins could be of particular importance, if an impaired antigen processing (e.g. in a post-transplant setting) must be taken into account.
Clinical significance of circulating tumor cells and metabolic signatures in lung cancer after surgical removal
Authors: Yang Dawei , Yang Xiaofang , Li Yang , Zhao Peige , Fu Rao , Ren Tianying , Hu Ping , Wu Yaping , Yang Hongjun , Guo Na 
Published: June 2020

Abstract
Background
Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain.

Methods
Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes.

Results
LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC before surgery. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 147 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA (LC patients after surgery) and LB (LC patients before surgery) groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC.

Conclusions
These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.
Examining working mothers’ experience of exclusive breastfeeding in Ghana
Authors: Abekah-Nkrumah Gordon , Antwi Maame Yaa , Nkrumah Jacqueline , Gbagbo Fred Yao 
Published: June 2020

AbstractBackgroundAlthough substantial evidence exists on factors that influence exclusive breastfeeding, there is a general lack of qualitative studies that examine how specific workplace factors constrain or promote exclusive breastfeeding among working mothers. The current study therefore examines working mothers’ experience of exclusive breastfeeding, laying emphasis on the influence of workplace factors on working mothers’ decision to exclusively breastfeed their babies.MethodsThe study uses a qualitative research approach and a three-stage purposive sampling procedure to select 20 mothers from 10 organizations in five industries for in-depth interviews on their exclusive breastfeeding experience. Data collected from the interviews were analysed using content analysis, with two major themes emerging for discussion.ResultsThe results suggest that two major factors influence exclusive breastfeeding among working mothers: practice of exclusive breast feeding (knowledge and understanding of exclusive breastfeeding, and experience in exclusive breastfeeding) and workplace factors (length of maternity leave, closing time, absence of maternity policy in organizations, inadequate institutional support and family work-life balance).ConclusionThe results of the study suggest that workplace factors play an equally crucial role in the decision by mothers to exclusively breastfeed their babies. Thus, in the special case of working mothers where breastfeeding prevalence is low, the findings of this study can be crucial in evolving appropriate policies to support working mothers in their effort to exclusively breastfeed their babies.
Radioprotective efficacy of plastic polymer against the toxicogenomic effects of radiopharmaceutical 18F-FDG on human lymphocytes
Authors: Lopes Nilson Benedito , Almeida Igor Vivian , Lopes Pedro Henrique Silvestre , Vicentini Veronica Elisa Pimenta 
Published: June 2020

Abstract
Background
Healthcare workers occupationally exposed to 18F-FDG cannot wear protective equipment, such as lead aprons, since the interaction between high energy radiation (511 keV) and metal increases the dose of radiation absorption. The objective of this study was to evaluate the shielding efficacy of a plastic polymer against the toxicogenomic effects of ionizing radiation in human lymphocytes, using cytokinesis-block micronucleus assays.

Methods
Human peripheral blood lymphocytes were isolated from three subjects and cultured under standard conditions. The cultures were exposed to 300 mCi of 18F-FDG at a distance of 10 cm for 10 min, in the absence of shielding or with lead, polymer, and lead + polymer shields.

Results
Lead shielding was found to increase the number of counts detected by Geiger-Müller radiation monitors as a consequence of the photoelectron effect. Conversely, the lead + polymer shield reduced the number of counts. The lead, polymer, and lead + polymer shields significantly reduced the frequency of micronuclei, nucleoplasmic bridges, and nuclear buds induced by ionizing radiation. Regarding cytotoxicity, only the lead + polymer shield re-established the cell cycle at the level observed for the negative control.

Conclusions
Lead aprons that are internally coated with polymer increased the radiological protection of individuals occupationally exposed to 18F-FDG PET/CT, especially during examinations.
Effect of symmetrical restoration for the migration of uncemented total hip arthroplasty: a randomized RSA study with 75 patients and 5-year follow-up
Authors: Kiernan Sverrir , Geijer Mats , Sundberg Martin , Flivik Gunnar 
Published: June 2020

Abstract
Background
Inferior placement of a femoral stem is predictive for early loosening and failure, but does restoration of the original hip anatomy benefit the function and survival of a total hip replacement?

Methods
Seventy-five patients with primary unilateral hip osteoarthritis operated with an uncemented anatomical stem were randomized for either standard or modular stems. We used 50 ABG II stems with modular necks and 25 standard stems (control group). We measured the symmetry in hip anatomy between healthy and operated side. The anatomical restoration variables were anteversion, global offset, and femoral offset/acetabular offset (FO/AO) quota. We performed measurements using a CT-based 3D templating and measuring software. Migratory behavior of the stems was then measured postoperatively with repeated radiostereometry (RSA) examinations over 5 years.

Results
Both stem types showed an early (within 3 months) good stabilization after an initial slight rotation into retroversion and subsidence. There were no significant differences in RSA migration between modular and standard stems. Postoperative anteversion and FO/AO quota had no impact on stem migration. The standard stem tended to result in insufficient global offset (GO), whereas the modular stem did not.

Conclusions
The modular stem gave good symmetrical anatomical restoration and, like the standard version, a benign migratory behavior. Anteversion, GO, and FO/AO quota had no significant impact on stem migration. It therefore seems to be of no importance whether we choose a modular or a standard stem with regard to postoperative stem migration for this stem type. We overestimated the effect anatomical parameters have on stem movement; hence, we believe the study to be underpowered.

Trial registration
ClinicalTrials.gov identifier: NCT01512550. Registered 19 January 2012—retrospectively registered,
Identification of therapeutic targets from genetic association studies using hierarchical component analysis
Authors: Lee Hao-Chih , Ichikawa Osamu , Glicksberg Benjamin S. , Divaraniya Aparna A. , Becker Christine E. , Agarwal Pankaj , Dudley Joel T. 
Published: June 2020

Abstract
Background
Mapping disease-associated genetic variants to complex disease pathophysiology is a major challenge in translating findings from genome-wide association studies into novel therapeutic opportunities. The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues.

Results
We present a novel strategy, called GWAS component analysis, for transferring disease associations from single-nucleotide polymorphisms to co-expression modules by stacking models trained using reference genome and tissue-specific gene expression data. Application of this method to genome-wide association studies of blood cell counts confirmed that it could detect gene sets enriched in expected cell types. In addition, coupling of our method with Bayesian networks enables GWAS components to be used to discover drug targets.

Conclusions
We tested genome-wide associations of four disease phenotypes, including age-related macular degeneration, Crohn’s disease, ulcerative colitis and rheumatoid arthritis, and demonstrated the proposed method could select more functional genes than S-PrediXcan, the previous single-step model for predicting gene-level associations from SNP-level associations.