bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of Exosomal miR-26a-5p Promotes Lymphangiogenesis and Lymphatic Metastasis in Endometrial Cancer
Authors: Wang Jing , Gong Xiaodi , Yang Linlin , Li Lijuan , Gao Xiaoyan , Ni Ting , Yang Xiaoming , Fan Qiong , Cui Yunxia , Sun Xiao , Wang Yudong 
Published: September 2021

Abstract
Background: Endometrial cancer (EC) patients with lymph node (LN) metastasis have poor prognosis. However, the potential biomarkers that predict LN metastasis and the molecular mechanism of tumor-induced peritumoral lymphangiogenesis have not been well explored. Cancer-secreted exosomal miRNAs are emerging mediators of cell-cell communication in the tumor environment.Methods: Exosomes were isolated with a differential centrifugation method and confirmed by Transmission electron microscopy, NanoSight analysis, and Western blot. MicroRNA (miRNA) sequencing of exosomes derived from EC patients and healthy donors were performed. FISH and qRT-PCR were used to detect the indicated miRNA expression. Exosomal miRNA transferred to cells were confirmed by immunofluorescence and confocal microscope. siRNA and plasmid transfections as well as viral infection were performed to manipulate gene expression. A series of in vitro and in vivo phenotype experiments (tube formation, migration, and popliteal LN metastasis model) were performed to investigate the role of indicated miRNA in EC. RNA sequencing was used to select the underlying transcription factor, and luciferase activity assay and chromatin immunoprecipitation were performed to elucidate the molecular mechanisms. Results: Our data showed that serum exosomal miR-26a-5p was significantly reduced in EC patients, and its level was positively associated with LN metastasis. Loss of miR-26a-5p promoted the migratory and invasive abilities of EC cells, and miR-26a-5p could be transferred from EC cells-secreted exosomes into human lymphatic endothelial cell (HLEC). Mechanistically, miR-26a-5p could regulate LEF1/c-myc/VEGFA axis via binding to its direct downstream target lymphoid enhancer binding factor 1 (LEF1), consequently promoting HLEC tube formation and migration in vitro, facilitating lymphangiogenesis and LN metastasis in vivo. Re-expression and knockdown of LEF1 could respectively promote and rescue the effects induced by exosomal miR-26a-5p. Moreover, we demonstrated that transcriptional factor EB (TFEB) directly induced miR-26a-5p expression.Conclusions: Our results show that exosomal miR-26a-5p/LEF1/c-myc/VEGFA axis is dysregulated and plays a critical role in LN metastasis and exosomal miR-26a-5p may be used as a blood-based biomarker for EC patients with LN metastasis.
Petrographic Composition of the Coal Within the Benue Trough, Nigeria, With a Consideration of the Paleodepositional Setting
Authors: Mangs Ayuba Danmangu , Wagner Nikki Jane , Moroeng Mavin Ofentse , Lar Uriah Alexander 
Published: September 2021

Abstract
The petrographic composition of coals hosted in the Benue Trough, Nigeria are presented and discussed in terms of paleodepositional setting that influenced the coal-bearing formations. The Benue Trough is a failed arm of the triple ‘RRr’ junction of an inland sedimentary basin that extends in a NE-SW direction from the Gulf of Guinea in the south, to the Chad Basin in the north. A total of twenty-nine (29) coal samples were obtained from 19 coal localities in the Upper (UBT), Middle (MBT), and Lower Benue Trough (LBT). The proximate data indicates the coal samples have a high volatile matter content, low ash yield, and high calorific value (24.82 MJ/Kg, on average). The sulphur values are generally low (average of 0.94 %). The coal samples are generally high in vitrinite, with an average of 59.3% by volume (mineral-matter free). Variation was noted in the inertinite content for the three sub-region samples. Liptinite macerals were not commonly observed in the studied samples and are absent in the MBT samples. The MBT coal samples reported a higher gelification index than the UBT and the LBT samples. Comparison of the array of coal facies models show the MBT samples are different from the UBT and LBT samples, concurring with the characterisation data. In view of the modified equations and the plots used, interpreting depositional environment accurately from just a single model is quite challenging.
One pot three component synthesis of substituted 3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-9,10-diphenylacridine-1,8(2H,5H,9H,10H)-diones catalyzed by efficient In2O3-SiO2
Authors: Tayde Deepak Totaram , Navgire Madhukar E. , Lande Machhindra K. 
Published: September 2021

Abstract
A convenient, One pot synthesis of heterocyclic nucleous acridine derivative compound has been achieved those are having very much attention in medicinal chemistry because of their extensive application in biology. The mixture of dimedone, substituted benzaldehyde and aniline were catalyzed by efficient In2O3-SiO2 heterogeneous reusable catalyst in ethanol to obtain the desired acridine derivatives with good yield. Hydrothermal method used to synthesize In2O3-SiO2 catalytic material. This catalytic material were characterized by using X-ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM), Energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), Transmission electron microscope (TEM), Temperature-programmed desorption (NH3-TPD) and Brunauer-Emmett-Teller (BET). Our synthetic strategy features high yield, simple work up procedure, non-toxic, clean, and easy recovery and reusability of the catalytic system.
Cisplatin-based Concurrent Chemoradiotherapy Improved the Survival of Locoregionally Advanced Nasopharyngeal Carcinoma After Induction Chemotherapy by Reducing Early Treatment Failure
Authors: Yang Xing-Li , Zhang Lu-Lu , Kou Jia , Zhou Guan-Qun , Wu Chen-Fei , Sun Ying , Lin Li 
Published: September 2021

Abstract
PurposeLimited data are available on the time course of treatment failures and the nature and duration of concurrent cisplatin benefit in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC).MethodsIn total, 3123 patients with stage III-IVa NPC receiving IC followed by concurrent cisplatin or not were analysed. The cut-off value of treatment failure was calculated using the minimum P-value approach. Random survival forest (RSF) model was to simulate the cumulative probabilities of treatment failure (locoregional recurrence and /or distant metastasis) over-time, as well as the monthly time-specific, event-occurring probabilities, for patients at different treatment groups. ResultsBased on subsequent prognosis, early locoregional failure (ELRF) should be defined as recurrence within 14 months (P = 1.47×10-3), and early distant failure (EDF) should be defined as recurrence within 20 months (P = 1.95×10-4). A cumulative cisplatin dose (CCD) > 200 mg/m2 independently reduced the risk of EDF (hazard ratio (HR), 0.351; 95% confidence interval (CI), 0.169-0.732; P = 0.005). Better failure-free survival (FFS) and overall survival (OS) were observed in concurrent chemotherapy settings ([0 mg/m2 vs. 1-200 mg/m2 vs. >200 mg/m2]: FFS: 70.4% vs. 74.4% vs. 82.6%, all P < 0.03; OS: 79.5% vs. 83.8% vs. 90.8%, all P < 0.01). In the monthly analysis, treatment failure mainly occurred during the first 4 years, and the risk of distant failure in patients treated with concurrent chemotherapy never exceeded that of patients without concurrent chemotherapy.ConclusionLocoregional failure that developed within 14 months and/or distant failure within 20 months had poorer subsequent survival. Concurrent chemotherapy provides a significant FFS benefit, primarily by reducing EDF, translating into a long-term OS benefit.
Clinical-pathological Characteristics and Prognostic Factors for Malignant Peritoneal Mesothelioma in the Elderly
Authors: Pan Dan , Wang Mengyao , Liu Wencheng , Li Yan , Sang Lixuan , Chang Bing 
Published: September 2021

Abstract
Background: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in the elderly. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in the elderly MPM patients.Methods: From the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥65) and the adult group (<65). We compared the clinical-pathological characteristics and treatment methods of elderly group (N=665) and adult group (N=827). At the same time, we analyzed specific selected clinical-pathological parameters and prognostic factors for the elderly MPM patients.Results: Compared with the adult group, the elderly group had a higher percentage of male patients (P = 0.017), white patients (P = 0.043), a lower proportion of insured patients (P < 0.001), married patients (P < 0.001), patients with peritoneal tumors (P = 0.006), patients who underwent surgery (P < 0.001), and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). The elderly patients had a shorter median survival time compared with the adult patients (6 months vs 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR: 3.913, P <0.001), poorly differentiated (HR: 3.900, P < 0.001), distant metastasis (HR: 1.735, P = 0.001), no cancer-directed surgery (HR: 1.733, P < 0.001), and no chemotherapy (HR: 1.532, P < 0.001) were independently associated with poorer prognosis of elderly MPM patients.Conclusion: Compared with the adult patients, elderly MPM patients had higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.
A comparative dosemetric study of bilateral breast cancer after modified radical mastectomy with HT and VMAT
Authors: Liu Xuhong , Xia Yaoxiong , Chang Li , Chen Xiao 
Published: September 2021

Abstract
Background: The purpose of this study was to compare the dosimetric differences in helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) plans of bilateral breast cancer after modified radical mastectomy.Methods: Ten patients with synchronous bilateral breast cancer (SBBC) who received modified radical mastectomy were selected for study. Two radiotherapy treatment plans, including HT and VMAT, were created for each patient. The prescribed doses of bilateral breast cancer and dual target volumes were given 25 times at 50Gy. The dosemetric parameters of planning target volume (PTV) and organs at risk (OARs) between HT and VMAT plans were compared and evaluated. Results: For PTV, HT had a higher V95 than that of VMAT plans (99.23 ± 0.61 % vs 98.17± 1.08 %, p=0.024). The conformity index (CI) between two techniques was statistically equivalent (0.812 ± 0.03 vs 0.793 ± 0.04, p=0.322) and the homogeneity index (HI) was reduced from 0.127 to 0.105 (p=0.007) when compared with that of VMAT. For OARs, HT had significantly lower Dmax for spinal cord and V5 for heart when compared with those of VMAT plans (16.68 Gy and 20.93% vs 38.82 Gy and 30.26%, respectively) (p<0.001). HT plans showed significantly lower V5, V10 and V20, that resulted in lower Dmean for the lungs (13.38 Gy vs 14.28Gy, p=0.013). However, VMAT showed specific advantages on V10, V20 and V30 for the heart and V5 and V10 for the liver when compared with those of HT plans (p<0.01). The Dmean for the heart and liver between the two techniques was not significantly different (p>0.05). HT plans also showed greater monitor units (MUs) and beam on time. Conclusion: HT had better PTV coverage and HI and showed better protections for the spinal cord and lungs compared with those of VMAT plans. HT plans effectively reduced the low-dose volume (V5) of the heart, while VMAT plans reduced V10, V20 and V30 for the heart. Both HT and VMAT plans exhibited similar Dmean for the heart and liver. The treatment efficiency of VMAT is higher than that of HT plans, and therefore, physicians need to choose a reasonable radiotherapy plan according to patient's conditions.
Critical Re-evaluation of the Slope Factor of the Operational Model of Agonism Short Title: Slope Factor of the Operational Model of Agonism
Authors: Jakubík Jan , Randáková Alena , Nelic Dominik 
Published: September 2021

Abstract
Although being a relative term, agonist efficacy is a cornerstone in the proper assessment of agonist selectivity and signalling bias. The operational model of agonism (OMA) has become successful in the determination of agonist efficacies and ranking them. In 1985, Black et al. introduced the slope factor to the OMA to make it more flexible and allow for fitting steep as well as flat concentration-response curves. Functional analysis of OMA demonstrates that the slope factor implemented by Black et al. affects relationships among parameters of the OMA. Fitting of the OMA with Black et al. slope factor to concentration-response curves of experimental as well as theoretical data (homotropic allosteric modulation, substrate inhibition and non-competitive auto-inhibition) resulted in wrong estimates of operational efficacy and affinity. In contrast, fitting of the OMA modified by the Hill coefficient to the same data resulted in correct estimates of operational efficacy and affinity. Therefore OMA modified by the Hill coefficient should be preferred over Black et al. equation for ranking of agonism and subsequent analysis, like quantification of signalling bias, when concentration response curves differ in the slope factor.
Different Phases of ATS Use Call for Different Interventions: a Large Qualitative Study in Europe
Authors: Liebregts Nienke , Rigoni Rafaela , Petruželka Benjamin , Barták Miroslav , Rowicka Magdalena , Zurhold Heike , Schiffer Katrin 
Published: September 2021

Abstract
Background: Amphetamine Type Stimulants (ATS) are globally widely used. However, there is limited understanding of what influences different phases of ATS use, as well as whether this varies by type of ATS user (groups). The ATTUNE study investigated which factors shape individual ATS use patterns. In this article, we report on these phases into and out of ATS use, and propose a set of recommendations for prevention, harm reduction and treatment of the different phases of ATS use.Methods: Qualitative, semi-structured interviews (n= 237) were conducted in five different European countries with participants who had used ATS, varying from a few times in a lifetime to daily. Results: Most ATS users consumed amphetamine only (28%), followed by amphetamine and MDMA (17%). Yet, types of ATS used differed between the countries. We found that that ATS users have various motives for and dynamic patterns of ATS use with alternating phases of increase, continuation and decrease. Cessation was pursued in different ways and for diverse reasons, such as mental health problems and maturing out. Availability seemed not an issue, regardless of the type of user, phase or country.Conclusions: These findings demonstrate that tailor-made interventions are needed for the diverse user types and different phases or patterns of ATS use, to reduce possible harms of use. We recommended a set of interventions for the different ATS phases. These include drug checking services, peer-led information, self-management of ATS use, mental health support to help people cope with stressful life events and prevent uncontrolled use, and follow-up support after treatment.
Consistent Genes Associated With Structural Changes in Clinical Alzheimer’s Disease Spectrum
Authors: Xu Jinping , Wang Chao , Zhang Jinhuan , Zhuo Junjie , Hu Qingmao 
Published: September 2021

Abstract
Background:Previous studies showed no obvious symptoms but subtle structural brain changes in a long preclinical stage of Alzheimer's disease (AD), then localized cortical and sub-cortical atrophy in MCI, and spread aggressively to nearly whole brain neurodegeneration in AD. However, the neurobiological and pathogenic substrates underlying these structural changes across AD spectrum remain largely understood.Methods: We obtained structural MRI imaging from ADNI datasets, including 83 early-stage mild cognitive impairments (EMCI), 83 late-stage mild cognitive impairments (LMCI), 83 AD, and 83 normal controls (NC), and aimed to explore structural changes across the full clinical AD spectrum and their genetic mechanism. Partial least square regressions and Spearman correlations were performed to explore how these changes associated with gene expression level obtained from Allen Human Brain Atlas. Finally, functional enrichment analyses were conducted using Metascape analysis to explore ontological pathways of the consistent genes. Results:We identified significant volume atrophy in left thalamus, left cerebellum, and bilateral middle frontal gyrus across AD spectrum. These structural changes were positively associated with gene expression levels of ABCA7, SORCS1, SORL1, PILRA, PFDN1, PLXNA4, TRIP4, and CD2AP, whereas were negatively associated with gene expression levels of CD33, PLCG2, APOE, and ECHDC3 for all three groups. Moreover, these results were verified in sub-groups of converted and stable EMCI and LMCI. Further gene enrichment analyses revealed that these positively associated genes were mainly involved in positive regulation of cellular protein localization and negative regulation of cellular component organization, whereas the negatively associated genes were mainly involved in positive regulation of iron transport. Conclusions:Overall, these results suggested that structural changes in prodromal and clinical AD might result from interaction of the same gene lists, which offered a better understanding of biological mechanisms underlying structural changes in prodromal and clinical AD.
Studies on the photoluminescence and thermoluminescence properties of CaZrO3:xEu3+
phosphor for dosimetric application
Authors: Fesharaki Marjaneh Jafari , Jalali Mohammad Reza , Karimi Leila , Sadeghi Ehsan 
Published: September 2021

Abstract
Series of CaZrO3:xEu3+ (x=0.01, 0.02, 0.03, 0.04 and 0.05) phosphors have been prepared by low temperature sol-gel auto combustion method. The structure and morphology of the samples were investigated by X-ray diffraction (XRD) and field-emission scanning electron microscope (FE-SEM). The energy-dispersive X-ray spectroscope (EDX) was employed to analyze the elemental composition of the phosphor. The XRD patterns indicated that the sample was single phase at 350 ◦C with a perovskite structure. The optimum temperature for the single- phase and crystalline phosphors of CaZrO3:xEu3+ was 700 ◦C. Study of photoluminescence (PL) at room temperature showed that the phosphors can be excited by light with a wavelength of 391 nm. The results of emission spectrum showed that the red luminescence of CaZrO3:xEu3+ due to electric dipole transition of 5D0→7F2 was dominant at wavelength of 615 nm and weaker transition at wavelength of 590 nm which was due to magnetic dipole transition of 5D0→7F1. For the thermoluminescence (TL) study the prepared sample irradiated by X-ray lamp, the TL curve was then recorded at fixed heating rate of 2 ◦C/s. The TL glow curve showed well single peak at a temperature of 165 ◦C. The effect of Eu3+ concentration at fixed X-ray exposure time was studied and maximum TL occurred at x=0.02. Also the variation of TL intensity with X-ray time (5 to 15 min) showed linear response with dose. The TL glow peak shows more stability and less fading in prepared phosphor which is suitable for TL dosimetry.
High serum concentrations of growth differentiation factor-15 in male Crohn’s disease patients with low skeletal muscle index
Authors: Yamamoto Hiroyuki , Takeshima Fuminao , Haraguchi Masafumi , Matsushima Kayoko , Kitayama Moto , Akazawa Yuko , Ogihara Kumi , Tabuchi Maiko , Hashiguchi Keiichi , Yamaguchi Naoyuki , Nakao Kazuhiko 
Published: September 2021

Abstract
Sarcopenia is defined as low skeletal muscle index (SMI) in addition to low muscle strength (MS) or low physical function, and many biomarkers have been reported. In Crohn's disease (CD), low SMI is associated with predictors and complications of intestinal resection. Therefore, in many reports of CD, sarcopenia was defined only by SMI. However, there have been no reports of MS in Japan. Our study aimed to investigate the frequency of sarcopenia by assessing both SMI and MS in Japanese patients with CD and biomarkers predicting low SMI. We evaluated SMI using bioelectrical impedance analysis, handgrip strength, and blood tests, including CRP, ALB, IL-6, TNFα, GDF-8, and GDF-15 as biomarker candidates for 78 CD patients in our hospital. Sarcopenia and low SMI were 8% and 42.3%, respectively. Each candidate biomarker and SMI were negatively correlated with GDF-15 (Pearson's r=-0.414, P = 0.0031) in males and positively correlated with ALB (r = 0.377, P = 0.048), and negatively correlated with IL-6 (r=-0.484, P = 0.012) in females. Multivariate analysis adjusted for these items, age, and BMI showed a significant difference in male GDF-15 (P = 0.011, OR: 7.86, 95% CI: 1.09–56.58). Therefore, GDF-15 in male patients is considered a biomarker of low SMI.
Changes of Gut Microbiota in Diabetic Nephropathy and Its Effect on the Progression of Kidney Injury
Authors: Cai Kedan , Ma Yanhong , Cai Fanghao , Huang Xiaohan , Xiao Liang , Zhong Chenyu , Ren Pingping , Luo Qun , Chen Jianghua , Han Fei 
Published: September 2021

Abstract
Background: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. Methods: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS respectively. After being built by streptozotocin (DM rats), the DM rats were administered 300mg/kg sodium butyrate for 12 weeks (DM+BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. Results: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen Ⅳ expressions in renal tissues in DM+BU rats. The LC3 mRNA, LC3BⅡ/Ⅰ ratio and number of autophagosomes were increased in renal tissue of DM+BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM+BU rats compared with DM rats. Conclusions: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.