bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Smoking on Progression from Ductal Carcinoma In Situ to Invasive Ductal Carcinoma: A Retrospective Study
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Kouhashi Rika , Yabumoto Akimichi , Ishihara Sae , Morisaki Tamami , Shibutani Masatsune , Tanaka Hiroaki , Hirakawa Kosei , Ohira Masaichi 
Published: January 2021

Abstract
Background: If ductal carcinoma in situ (DCIS) is diagnosed by histological examination such as core needle biopsy or vacuum-assisted biopsy (VAB), invasion is often found by removing the entire tumor and performing pathological examination. According to a meta-analysis, the rate of invasion found by postoperative pathological examination is about 25%. Smoking is a risk factor for carcinogenesis in various carcinomas, including breast cancer. We examined the correlation between the risk of invasion found by postoperative pathology and smoking history in patients who were diagnosed with DCIS by preoperative biopsy.Methods: In this study, we examined 128 patients who were diagnosed with DCIS by preoperative biopsy. Before the biopsy, all patients were asked about the duration of smoking, number of cigarettes smoked per day, and whether they were currently smoking. The data were used to calculate each patient’s tobacco exposure based on pack-years. The statistical analyses included the Pearson’s chi-square test and logistic analysis. Multivariate analysis was performed on the risk factors for invasion diagnosed by postoperative pathological examination in all cases diagnosed with DCIS by preoperative biopsy.Results: Of all the patients included in this study, 107 (83.5%) never smoked, which represented the majority, while 8 patients (6.3%) smoked at diagnosis with DCIS, and 13 (10.2%) had quit smoking before diagnosis. Tobacco exposure was 10 or less pack-years for 11 patients (8.6%) and more than 10 pack-years for 10 patients (7.8%). Number of pack-years was not an independent factor (p=0.349, odds ratio [OR]=0.329), but current smoker status (p=0.006, OR=not calculable) was an independent factor with VAB (p=0.018, OR=0.327).Conclusions: This study suggests that tobacco components may have an influence on the progression from DCIS to invasive ductal carcinoma.
WITHDRAWN: Polymorphisms of Tumour necrosis factor-α-308 (rs 1800629) and gastric cancer susceptibility: A meta- analysis of associations studies with trial sequential analysis
Authors: Htet Norah Htet , Naing Cho , Tung Wong Siew , Win Thin Thin , Mak Joon Wah 
Published: January 2021

Abstract
Background: Gastric cancer is globally the fifth most common cancer. Several studies have assessed the relationship between tumour necrosis factor-alpha (TNF-a- 308) and the risk of gastric cancer. These individual genetic association studies showed inconclusive results. The objective of the present study was to synthesis evidence on the association between TNF-a-308 polymorphisms and gastric cancer risk by meta-analysis of data from eligible studies.Methods: We performed a meta-analysis of genetic association studies, according to the PLOS One checklist. We searched relevant case-control studies in health-related electronic databases. The methodological quality of included studies was assessed by the Newcastle-Ottawa quality assessment scale. The strength of association was calculated as odds ratios (ORs) with 95% confidence intervals (CIs). Pooled ORs and 95 % CIs were estimated using random-effects model or fixed effect model, based on between-study heterogeneity. We analysed the strength of association under four genetic models (allele, dominant, recessive and additive models). Subgroup analyses on ethnic groups, Hardy-Weinberg equilibrium (HWE) status, status of Helicobacter pylori infection and study quality were done for robustness of the estimates. Publication bias was detected by inspection of funnel plot asymmetry. To estimate the required information size, we performed trial sequential analysis (TSA) that classified the effect estimates as ‘firm evidence of effect’ or ‘potentially spurious evidence of effect’.Results: A total of 35 studies, comprising 11353 cases and 12827 controls were identified. Based on 28 studies that met HWE, there was overall significant association between TNF-α-308 polymorphisms and gastric cancer risk under the dominant model (OR 1.19, 95%CI 1.1-1.29, I2:37%), as well as Asians (OR 1.2, 95%CI 1.05-1.38, I2:53%) and Cassian subgroups (OR 1.19, 95%CI 1.07-1.31, I2:28%). Based on 13 high quality studies under the dominant model, overall significant association was also found (OR 1.38, 95%CI 1.07, 1.77). The TSA plot indicated the analyses was with the required information size. There was no publication bias. In the subgroup analysis by ethnic groups, the quality of studies impacted on the estimates. Conclusions: The findings suggest that TNF-α-308 gene polymorphism plays an important predisposing role for gastric carcinogenesis, and can serve as a useful screening marker.
Distinct Time Courses and Pathogenic Contributions of Alveolar Epithelial and Endothelial Injury in Acute Respiratory Distress Syndrome With COVID-19: Evidence From Circulating Biomarkers
Authors: Tojo Kentaro , Yamamoto Natsuhiro , Mihara Takahiro , Abe Miyo , Goto Takahisa 
Published: January 2021

Abstract
Background: In severe cases of coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS) with alveolar tissue injury occurs. However, the time course and specific contributions of alveolar epithelial and endothelial injury to the pathogenesis of COVID-19 ARDS remain unclear.Methods: We evaluated the levels of a circulating alveolar epithelial injury marker (soluble receptor for advanced glycation end-products: sRAGE) and an endothelial injury marker (angiopoietin-2: ANG-2), along with an alveolar permeability indicator (surfactant protein D: SP-D) in 107 serum samples from nine patients with ARDS and eight without ARDS, all with COVID-19, admitted to Yokohama City University Hospital from January to July 2020. We compared the initial levels of these markers between ARDS and non-ARDS patients, and analysed the temporal changes of these markers in ARDS patients. Results: All the initial levels of sRAGE (median: 2680 pg/mL, IQR:1522–5076 vs. median 701 pg/mL, IQR:344–1148.0, p=0.0152), ANG-2 (median: 699 pg/mL, IQR: 410-2501 vs. median: 231 pg/mL, IQR: 64-584, p=0.0464), and SP-D (median: 17542 pg/mL, IQR: 7423-22979 vs. 1771 pg/mL, IQR: 458-204, p=0.0274) were significantly higher in the ARDS patients than in the non-ARDS patients. The peak sRAGE level in the ARDS patients was observed at the very early phase of disease progression (median: day 1, IQR: day 1–3.5). However, the peaks of ANG-2 (median: day 4, IQR: day 2.5–6) and SPD (median: day 5, IQR: day 3–7.5) were observed at a later phase. Moreover, the ANG-2 level was significantly correlated with the arterial oxygenation (p=0.030) and the SPD level (p=0.002), but the sRAGE level was not. Conclusion: Evaluation of circulating markers confirms that COVID-19 ARDS is characterised by severe alveolar tissue injury. Our data indicate that the endothelial injury, which continues for a longer period than the epithelial injury, seems to be the main contributor to alveolar barrier disruption. Targeting the endothelial injury may, thus, be a promising approach to overcome ARDS with COVID-19.
Impaired Ventilation Is Not Independently Associated With 28-day Mortality in COVID-19 ARDS
Authors: Morales-Quinteros Luis , Neto Ary Serpa , Artigas Antonio , Blanch Lluis , Botta Michela , Kaufman David A , Schultz Marcus J , Tsonas Anissa , Paulus Frederick , Bos Lieuwe D 
Published: January 2021

Abstract
Background: Surrogates for impaired ventilation such as estimated dead-space fractions and the ventilatory ratio have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19 related ARDS. Methods: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicentre, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of impaired ventilation patients with COVID-19 related ARDS. Results: 927 consecutive patients admitted with COVID-19 related ARDS were included in this study. Surrogates of impaired ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p <0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p<0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and for the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the surrogates of impaired ventilation measured at the start of ventilation or the following days were significantly associated with 28-day mortality.Conclusions: There is significant impairment of ventilation in the early course of COVID-19 related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk-model.
Inequalities in Stunting Prevalence Among Children Under Age 5 in Ghana Between 1998 and 2014
Authors: Adu Collins , Ameyaw Edward Kwabena , Agbadi Pascal , Agbaglo Ebenezer , Tetteh Justice Kanor , Nutor Jerry John 
Published: January 2021

Abstract
BackgroundOver the years, Ghana has made significant improvements in the nutritional status of children, particularly concerning stunting. Though these improvements are commendable, there are concerns of inequalities in the prevalence of stunting among children under five. To this end, we examined the trends and inequalities in the determinants of stunting prevalence in children under five in Ghana, throughout 1998-2014.MethodsUsing the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) software, we analysed data from the 1998-2014 Ghana Demographic and Health Surveys (GDHS). We approached the inequality analysis in two steps. First, we disaggregated stunting prevalence among children < 5 years by five equity stratifiers: wealth index, education, sex, residence, and region. Second, we measured the inequality through summary measures, namely Difference, Population Attributable Risk, Ratio, and Population Attributable Fraction. A 95% confidence interval was constructed for point estimates to measure statistical significance.ResultsConcerning economic status, only the simple summary measures (Difference [D], Ratio [R]) showed significant inequality in stunting. For instance, both D (23.40; 17.55-29.25) and R (2.43; 1.78-3.09) revealed substantial economic variation in stunting in 1998 and the same trend was noted across all the survey years. The complex summary measures, however, showed a significant but negative association. Both D (16.36; 12.13-20.60) and R (1.90; 1.51-2.28) revealed a positive significant disparity in favour of urban residents in 1998. The simple measures further indicated a significant disparity in stunting at the detriment of male children throughout the period studied. Finally, a significant disparity at the expense of children in the Northern Region was evident in 1998 (D=31.00; R=3.22), 2003 (D=37.21; R=3.17) and 2014 (D=22.73; R=3.19).ConclusionInequalities in stunting prevalence in Ghana is to the disadvantaged children of poorest wealth quintile, mothers with no formal education, male children, rural residents and the Northern Region of Ghana. We recommend the introduction and strengthening of equitable interventions focusing on nutrition on sub-populations in the country who suffer from a higher burden of stunting.
miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN
Authors: Gao Bin , Wang Lijuan , Zhang Yubo , Zhang Na , Han Miaomiao , Liu Huancai , Sun Dongli , Xiao Xiaolong , Liu Yifei 
Published: January 2021

Abstract
Objective: Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods: Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis. Results: miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity.Conclusion: Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.
De novo sequencing and analysis of the transcriptome of two highbush blueberry (V. corymbosum L.) cultivars ‘Bluecrop’ and ‘Legacy’ at harvest and following post-harvest storage
Authors: Concepcion Maria Carcamo de la , Sargent Daniel James , Surbanovski Nada , Colgan Richard , Moretto Marco 
Published: January 2021

Abstract
Background: Fruit firmness and in particular the individual components of texture and moisture loss, are considered the key quality traits when describing blueberry fruit quality, and whilst these traits are genetically regulated, the mechanisms governing their control are not clearly understood. In this investigation, RNAseq was performed on fruits of two blueberry cultivars with very different storage properties, ‘Bluecrop’ and ‘Legacy’, at harvest, three weeks storage in a non-modified environment at 4 oC and after three weeks storage at 4 oC followed by three days at 21 oC, with the aim of understanding the transcriptional changes that occur during storage in cultivars with very different post-harvest fruit quality.Results: De novo assemblies of the transcriptomes of the two cultivars were performed separately and a total of 39,335 and 41,896 unigenes for ‘Bluecrop’ and ‘Legacy’ respectively were resolved. Differential gene expression analyses were grouped into four cluster profiles based on changes in transcript abundance between harvest and 24 days post-harvest. A total of 264 unigenes were up-regulated in ‘Legacy’ and down-regulated in ‘Bluecrop’, 103 were down-regulated in ‘Legacy’ and up-regulated in ‘Bluecrop’, 43 were up-regulated in both cultivars and 355 were down-regulated in both cultivars between harvest and 24 days post-harvest. Unigenes showing significant differential expression between harvest and following post-harvest cold-storage were grouped into classes of biological processes including stress responses, cell wall metabolism, wax metabolism, calcium metabolism, cellular components, and biological processes.Conclusions: In total 21 differentially expressed unigenes with a putative role in regulating the response to post-harvest cold-storage in the two cultivars were identified from the de novo transcriptome assemblies performed. The results presented provide a stable foundation from which to perform further analyses with which to functionally validate the candidate genes identified, and to begin to understand the genetic mechanisms controlling changes in firmness in blueberry fruits post-harvest.
Microbiological findings in early and late implant loss: an observational clinical case-controlled study
Authors: Korsch Michael , Marten Silke-Mareike , Stoll Dominic , Prechtl Christopher , Dötsch Andreas 
Published: January 2021

Abstract
Background Implants are a predictable and well-established treatment method in dentistry. Nevertheless, looking at possible failures of dental implants, early and late loss have to be distinguished. The intent of the study was to report microbiological findings on the surface of implants with severe peri-implantitis, which had to be explanted. Methods 53 specimens of implants from 48 patients without severe general illnesses have been examined. The groups investigated were implants that had to be removed in the period of osseointegration (early loss, 13 patients with 14 implants) or after the healing period (late loss, 14 patients with 17 implants). The implant losses were compared with two control groups (implants with no bone loss directly after completed osseointegration, two to four months after implant placement (17 patients with 17 implants) and implants with no bone loss and prosthetic restoration for more than three years (5 patients with 5 implants)). Data about the bacteria located in the peri-implant sulcus was collected using amplification and high throughput sequencing of the 16S rRNA gene. Results The biofilm composition differed substantially between individuals. Both in early and late implant loss of Fusobacterium nucleatum , and Porphyromonas gingivalis were found to be abundant . Late lost implants showed higher bacterial diversity and in addition higher abundances of Treponema, Fretibacterium, Pseudoramibacter and Desulfobulbus , while microbial communities of early loss implants were very heterogeneous and showed no significantly more abundant bacterial taxa. Conclusions Specific peri-implant pathogens were found around implants that were lost after a primarily uneventful osseointegration. P. gingivalis and F. nulceatum frequently colonized the implant in early and late losses and could therefore be characteristic for implant loss in general. In general, early lost implants showed also lower microbial diversity than late losses. However, the microbial results were not indicative of the causes of early and late losses.
Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10
Authors: Chen Fangyu , Xu Bing , Li Jie , Yang Xi , Gu Junjie , Yao Xijuan , Sun Xinchen 
Published: January 2021

Abstract
Background: Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear. Methods: Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.Results: Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis. Conclusions: Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.
Idārat Jūdat al-Ishrāf al-Lughawiy fi Tarqiyat Ta'līm al-Lughah al-‘Arabiyah bi Ma'had Jāmi‘ah Maulāna Mālik Ibrāhīm al-Islāmiyyah al-Ḥukūmiyyah Malang
Authors: Budiyah Bahroin 
Published: January 2021

<p style="direction: ltr;" dir="RTL">There is quality management with education subject who teach and guide college students in Arabic learning. Mushrifs is the santri’s companion in the first and second semester in Mahad Al-Jami’ah. In particular program, they teach Arabic in Mahad and conduct Arabic learning. The quality of Mushrifs of Language in improving Arabic learning is one of the objectives in order to generate good and success mushrifs in Mahad Al-Jami’ah. The research problems were: 1) How is the planning quality of language guidance in improving Arabic learning in mahad al-jami’ah, 2) how is the organization quality of language guidance in improving Arabic learning in mahad al-jami’ah, 3) how is the implementation of quality Supervision of language in improving the Arabic learning in mahad al-jami’ah, 4) how is the supervision quality of language guidance in improving Arabic learning in mahad al-jami’ah. This study aimed to describe the planning, organization, implementation, and supervision of quality management of mushrifs in improving the Arabic learning in Mahad Al-jam’ah. This study used descriptive analysis design, and the data collections were through observation, interview and documentation, and through all those things to research in data’s about the quality management of language guidance. The results of quality management of language guidance study in improving the Arabic learning were: 1) in the planning stage, the first process was opening the registration for mushrifs’ candidates with a very strict selection, 2) in the organization aspect was the cooperation relationship between the mahad director, murabbi, and mushrifs of language with their tasks, 3) in the implementation aspect was through PSDM, language enrichmen, shabah al-lugah, gebyar bahasa competition and bilingual seminar; 4) and in the supervision aspect was the supervision was conducted once in two weeks by murabbi of language.</p>