bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Conformational Luminescence and Phosphorescence of Few Phenazine 1,2,3-Triazole Molecules
Authors: Pinto Pablo B. , Cruz Kimberly C. T. da , Júnior Eufrânio Nunes da Silva , Cury Luiz Alberto 
Published: January 2022

Abstract
Dropcast films produced from blends solutions of phenazine 1,2,3-triazole molecules in very low concentrations in a 1,3-Bis (N-carbazolyl) benzene (mCP) matrix were investigated at room temperature. The mCP acts as an optically inert matrix, having no influence on the emission properties of the guest molecules. Its conductive properties also ensure that blend films, within a completely organic character, are formed as truly active layers. The fluorescent and phosphorescent emission properties of the phenazine molecules, depending on their conformational states, allowed relatively intense emissions in blue, green, red and also in white, without the need to mix different materials. Although the results of absorption of the blended films have shown no characteristics of the guest molecules, due to their relatively low concentrations, the excitation of them occurs directly by the incident laser beam. The steady-state spectroscopy for the monomer and dimer singlet fluorescence states of respective blue and green emissions of the films were investigated. The analysis of their temporal decays were done using a different approach based on the Exponentially Modified Gaussian (EMG) function. The phosphorescent emissions of the triplet steady-states, occurring in the orange or in the red wavelength regions, were observed to be correlated, respectively, to the formation of guest monomers or to the guest dimers singlet states.
NRF2 Participates in the Suppressive Tumor Immune Microenvironment of KRAS/KEAP1 Co-Mutant Non-Small Cell Lung Cancer by Inhibiting the STING Pathway
Authors: Sun Xiaodan , Zhao Peiyan , Li Hui , liu Yan , Cheng Ying 
Published: January 2022

Abstract
Background: KRAS/KEAP1 (KK) co-mutant lung adenocarcinoma (LUAD) exhibited poor response to immune checkpoint inhibitors (ICI) via shaping a suppressive tumor immune microenvironment, the mechanism remains to be elucidated. Methods: The mRNA and protein expression of target molecules were analyzed by qRT-PCR and Western blot, respectively. The subcellular location of NRF2 was observed by immunofluorescence staining, and nuclear and cytoplasm isolation. After exogenous over-expression and knockdown of NRF2 and the addition of a STING pathway inhibitor in tumor cells, the effects on the CD8+ T cell recruitment was detected using chemotaxis assay, and the secretion of chemokines CCL5 and CXCL10 was analyzed by ELISA. The potential NRF2 target BRCA1 was identified using bioinformatic approaches and verified by a dual luciferase reporter assay. Results: NRF2, the target of KEAP1, was overexpressed and activated in KK type cells. NRF2 effected as a negative regulator of CD8+ T cells recruitment by decreasing CCL5 and CXCL10 chemokines in KK type LUAD. Mechanistically, NRF2 promoted the transcription and expression of BRCA1 to repair DNA damage, resulting in STING pathway inactivation. Conclusion: The combination of NRF2 inhibitor or STING agonist with ICI may be a promising therapeutic approach for patients with KK type LUAD.
Using Threshold Analysis to Assess the Robustness of Public Health Intervention Recommendations from Network Meta-Analyses: Application to Poison Prevention in Households with Children Under Five
Authors: Wells Molly , Bujkiewicz Sylwia , Hubbard Stephanie J 
Published: January 2022

Abstract
BackgroundIn the appraisal of clinical interventions, complex evidence synthesis methods, such as network meta-analysis (NMA), are commonly used to investigate the effectiveness of multiple interventions in a single analysis. The results from a NMA can inform clinical guidelines directly or be used as inputs into a decision-analytic model assessing the cost-effectiveness of the interventions. However, there is hesitancy in using complex evidence synthesis methods when evaluating public health interventions. This is due to significant heterogeneity across studies investigating such interventions and concerns about their quality. Threshold analysis has been developed to help assess and quantify the robustness of recommendations made based on results obtained from NMAs to potential limitations of the data. Developed in the context of clinical guidelines, the method may prove useful also in the context of public health interventions. In this paper, we illustrate the use of the method in the study investigating the effectiveness of interventions aiming to increase the uptake of poison prevention behaviours in homes with children aged 0-5.MethodsRandom effects NMA was carried out to assess the effectiveness of several interventions for increasing the uptake of poison prevention behaviours, focusing on the safe storage of other household products outcome. Threshold analysis was then applied to the NMA to assess the robustness of the intervention recommendations made based on the NMA.Results15 studies assessing seven interventions were included in the NMA. The results of the NMA indicated that complex intervention, including Education, Free/low-cost equipment, Fitting equipment and Home safety inspection, was the most effective intervention at promoting poison prevention behaviours. However, the threshold analyses highlighted that this intervention recommendation was not robust.Conclusions In our case study, threshold analysis allowed us to demonstrate that the intervention recommendation for promoting poison prevention behaviours was not robust to changes in the evidence due to potential bias. Therefore, caution should be taken when considering such interventions in practice. We have illustrated the potential benefit of threshold analysis and, therefore, encourage the use of the method in practice as a sensitivity analysis for NMA of public health interventions.
Predictor Naïve Temporal Baseline Hazard of Recurrent Ischemic Stroke
Authors: Elhefnawy Marwa Elsaeed , Ghadzi Siti Maisharah Sheikh , Albitar Orwa , Tangiisuran Balamurugan , Zainal Hadzliana , Looi Irene , Sidek Norsima , Aziz Zariah Abdul , Harun Sabariah Noor 
Published: January 2022

Abstract
There are established correlation between risk factors and the recurrence of ischemic stroke (IS), however does the hazard of recurrent IS change although without the influence of established risk factors? This study aimed to quantify the hazard of recurrent IS at different time points after the index IS. This was a population cohort study extracted data of 7697 patients with a history of first IS attack registered with National Neurology Registry of Malaysia. A repeated time to recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility and visual predictive checks. Three hundred and thirty-three (4.32%) patients developed at least one recurrent IS within the maximum 7.37 years follow-up. In the absence of significant risk factors, the hazard of recurrent IS was predicted to be 0.71 within the first month after the index IS and reduced to 0.022 between the first to third months after the index attack. The hazard of IS recurrence accelerated with the presence of typical risk factors such as hyperlipidaemia (HR, 2.64 [2.10-3.33]), hypertension (HR, 1.97 [1.43-2.72], and ischemic heart disease (HR, 2.21 [1.69-2.87]). In conclusion, the absence of significant risk factors, predicted hazard of recurrent IS was prominent in the first month after the index IS and was non-zero even three months after the index IS or later. Optimal secondary preventive treatment should incorporate the ‘nature risk’ IS recurrence.
Dexmedetomidine Induces Microglial Activation and Modulates Microglial M1/M2 Polarization in Attenuation of Chronic Morphine Tolerance in Cancer Pain
Authors: Bu Jianlong , Xiaohong Wu , Lin Deng , Chao Ma , Xiaoding Shi , ZHANG PINYI , Guonian Wang 
Published: January 2022

Abstract
The pro-inflammatory (M1) and anti-inflammatory (M2) status of microglial determines the outcome of neuroinflammation, which contributes to the pathogenesis of chronic morphine tolerance. Studies report that α2-adrenoceptor agonist dexmedetomidine exerts anti-inflammatory effects in inhibiting morphine tolerance in normal and neuropathic pain animals, which has not been studied in cancer pain. Therefore, we investigate the effect of intrathecal DEX on morphine tolerance in cancer pain, and whether dexmedetomidine functions via modulating microglial activation and M1/M2 polarization. 54 Wistar rats with intrathecal catheterization were treated by morphine for 10 days. Test groups received intrathecal α2-adrenoceptor agonist dexmedetomidine or antagonist MK-467. The mRNA levels of TLR4 and NF-κB were tested by RT-PCR. The protein levels of TLR4, NF-κB, Iba-1, iNOS, CD206 were quantifed using Western blotting, and IL-10 and TNF-α were examined by ELISA. Dexmedetomidine attenuates mechanical threshold and thermal latency, and increased the expression of TLR4 and NF-κB in morphine tolerance of cancer pain. Dexmedetomidine attenuates mechanical and thermal nociception in morphine tolerance in cancer pain rats. Intrathecal DEX pre-treatment significantly increased the protein levels of microglia maker Iba-1, M2 marker CD206 and anti-inflammatory factor IL-10, while had no evident influence on the pro-inflammatory factor TNF-α and M1 marker iNOS in morphine tolerance. Our findings suggest that intrathecal dexmedetomidine attenuates morphine tolerance in cancer pain via α2-adrenoceptor pathway. Furthermore, dexmedetomidine upregulates TLR4/NF-κB pathway and induces microglia activation in chronic morphine tolerance of cancer pain. The anti-inflammatory effect of dexmedetomidine might be exerted by inducing microglia M2 polarization and increasing anti-inflammatory factor IL-10.
Prevalence and Burden of Gastrointestinal Parasites in Stray Cattle of Kathmandu Valley
Authors: Thapa Bigyan , Parajuli Rajendra Prasad , Dhakal Pitambar 
Published: January 2022

Abstract
Gastrointestinal parasites (GIPs) are ubiquitous among cattle resulting severe infection. Prevalence of GIPs in stray street cattle may pose risk of dissemination of parasites of zoonotic importance. This study was conducted to determine the prevalence of GIPs in stray cattle of Kathmandu valley. Hundred (n=100) freshly voided dung samples were collected from eight places. The samples were processed using concentration method for microscopic examination, and modified McMaster technique for quantification of mean eggs/oocysts per gram of feces (EPG/OPG). Results revealed that 72% of the cattle were found positive for one or more species of GIPs and nine genera of GIPs were recorded (Eimeria, Ostertagia, Haemonchus, Trichostrongylus, Capillaria, Trichuris, Toxocara, Fasciola and Paramphistomum). The prevalence of parasitic infection was higher in male (73.68%) than in female (69.76%). The prevalence was found to be highest in adults (63.89%) followed by heifers (27.78%) and calves (8.33%). Approximately 76% of the cross breed and 65% local breed of cattle were positive for parasitic infection. The parasites differed both in prevalence and intensity, Eimeria sp. being the most prevalent (27%) with highest intensity (858.02 OPG ±63.46 SD). To our information, this is the first research of its kind in relation to stray cattle in Nepal. Our findings reveal that there is burden of helminth infections of zoonotic and socioeconomic importance in the straycattle. Therefore, it warrants regular inspection, relevant preventive measures and molecular detection of parasites.
The Clinical Impact of Neoadjuvant Endocrine Treatment On Luminal-Like Breast Cancers and Its Prognostic Significance: Results From a Single-institution Prospective Cohort Study
Authors: Martí Covadonga , Yébenes Laura , Oliver José María , Moreno Elisa , Frías Laura , Berjón Alberto , Loayza Adolfo , Meléndez Marcos , Roca María José , Córdoba Vicenta , Hardisson David , Rodríguez María Ángeles , Sánchez-Méndez José Ignacio 
Published: January 2022

Abstract
Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast conserving surgery (BCS) rates, and provides an opportunity for assessing in vivo NET effectiveness and studying any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness.Methods: From 2016 to 2020, a single-institution cohort of patients treated with NET and further surgery was evaluated. In patients with Ki67≥10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered.Results: A total of 115 estrogen receptor positive (ER+)/HER2 negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0-6.0). Median maximum size in the surgical sample was 40% smaller than pretreatment size measured by ultrasound (p<.0001). Median pretreatment Ki67 expression was 20.0% (IQR: 12.0-30.0), and was reduced to 5.0% (IQR: 1.8-10.0) after four weeks, and to 2.0% (IQR: 1.0-8.0) in the surgical sample (p<.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold-change after four weeks was significantly related to a PEPI score of 0 (p<.002). No differences were observed between luminal A- and B-like tumors with regard to fold-change and PEPI score.Conclusions: In our cohort, NET has proven effective for tumor size and Ki67 downstaging. This results in a higher rate of conservative surgery, aids in therapeutic decision-making, provides prognostic information, and constitutes a safe and well-tolerated approach
Denosumab-Induced Medication-Related Osteonecrosis of the Jaw (DRONJ): A 5-Year Retrospective Cohort Study
Authors: Kim JaeYeon , Jung Seoyeon , Park Jin Hoo , Kim Hyung-Jun , Park Wonse 
Published: January 2022

Abstract
Denosumab (Dmab) has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of Dmab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. Thus, we investigated the factors that can affect Dmab induced MRONJ (DRONJ) to elucidate the relationship between invasive dental treatment and Dmab administration in patients who underwent Dmab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. Two out of 4 patients developed MRONJ regardless of invasive treatment after Dmab administration and proceeded with extraction, and one patient developed DRONJ after Dmab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and spontaneous DRONJ developed after Dmab administration. All MRONJ/DRONJ cases reported in this study show that MRONJ/DRONJ can develop as chronic inflammation without invasive dental treatment, therefore, implementing preventive dental treatment before initiating Dmab treatment is necessary to reduce the likelihood of DRONJ.
Establishment and Evaluation of a Risk-prediction Model for HBP in Elderly Patients With NAFLD From a Health Management Perspective
Authors: Luo Xin , Zhang An , Pan Hong , Shen Xinxin , Liu Baocheng , Li Dong , Sun Jijia 
Published: January 2022

Abstract
Objective: Elderly patients with nonalcoholic fatty liver disease (NAFLD) are at a higher risk of developing high blood pressure (HBP) and having a low quality of life. This study established an effective, individualised, early HBP risk-prediction model and proposed health management advice for the ³60 patients with NAFLD in Shanghai, China.Methods: Questionnaire surveys, physical examinations, and biochemical tests were conducted on 7,319 cases of sample data. Risk factors were screened using the least absolute shrinkage and selection operator (Lasso) model and random forest (RF) model. A risk-prediction model was established using logistic regression analysis and dynamic nomogram was drawn. The model was evaluated for discrimination, calibration, and clinical applicability using receiver operating characteristic curves (ROC), calibration curves, decision curve analysis (DCA), net reclassification index (NRI), and external validation.Results: The results suggested the model showed moderate predictive ability. The area under curve (AUC) of internal validation was 0.707 (95% CI: 0.688-0.727), the external validation AUC was 0.688 (95% CI: 0.672-0.705). The calibration plots showed good calibration, the risk threshold of the decision curve was 30-56%, and the NRI value was 0.109.Conclusion: This HBP risk factor model may be used in clinical practice to predict the HBP risk in NAFLD patients.
H3K27me3 at Pericentromeric Heterochromatin is a Defining Feature of the Early Mouse Blastocyst
Authors: Pailles Mélanie , Hirlemann Mélanie , Brochard Vincent , Chebrout Martine , Oudin Jean-François , Jouneau Alice , Bonnet-Garnier Amélie 
Published: January 2022

Abstract
Early mouse development is characterized by structural and epigenetic changes at the chromatin level while cells progress towards differentiation. At blastocyst stage, the segregation of the three primordial lineages is accompanied by establishment of differential patterns of DNA methylation and post-translational modifications of histones, such as H3K27me3. In this study, we have analysed the dynamics of H3K27me3 at pericentromeric heterochromatin (PCH) during development of the mouse blastocyst, in comparison with cultured embryonic cells. We show that this histone modification is first enriched at PCH in the whole embryo and evolves into a diffuse distribution in epiblast during its specification and maturation. Concomitantly, the level of transcription from major satellite decreases. Stem cells derived from blastocyst (naïve ESCs and TSCs) do not fully maintain the H3K27me3 enrichment at PCH. Moreover, the dynamic of H3K27me3 at PCH during in vitro conversion from naïve to primed pluripotent state and during ESCs derivation suggests that the mechanisms underlying the control of this histone mark at PCH are different in embryo and in vitro. We also conclude that the non-canonical presence of H3K27me3 at PCH is a defining feature of embryonic cells in the young blastocyst before epiblast segregation.
Comparison of Convolutional Neural Networks Based Method and LCmodel on the Quantification of in Vivo Magnetic Resonance Spectroscopy
Authors: Huang Yu-Long , Lin Yi-Ru , Tsai Shang-Yueh 
Published: January 2022

Abstract
Quantification of metabolites concentrations in institutional unit (IU) for between subject and long-term comparison is considered important strategy in the applications of magnetic resonance spectroscopy (MRS). The aim of this study is to investigate if metabolite concentrations quantified by convolutional neuronal network (CNN) based method associated with a proposed scaling procedure can reflect variations of the metabolite concentrations in institution unit (IU) at different brain regions with different signal-to-noise-ratio (SNR) and linewidth (LW). An error index based on standard error (SE) is proposed to indicate the confidence levels on the prediction for metabolites. In vivo MRS spectra were collected at 3 brain regions from 44 subjects at 3T system. Metabolite concentrations in IU quantified by LCModel and CNN from 44 subjects were compared. For in vivo spectra characterized under different spectral quality in terms of SNR and LW, line narrowing and noise free spectra were successfully exported by CNN. Concentrations of five metabolites quantified by CNN and LCModel are in similar range with statistically significant Pearson’s correlation coefficients (0.28~0.70). SE of the metabolites show positive correlation with Cramer-Rao lower bound (CRLB) (r=0.60) and with absolute CRLB (r=0.84). In conclusion, the CNN based method with the proposed scaling procedures can be used to quantify in vivo MRS spectra. The concentrations of five major metabolites were reported in IU, which are in the same range as those quantified using a routine MRS quantification procedures by LCModel. The SE can be used as error index indicating predicted uncertainties for metabolites with the information similar to the absolute CRLB.
Unified Phase Field Theory Based on the Interaction of Positive and Negative Magnetic poles and Analysis of ATLAS, CMS Experiment at the LHC
Authors: wu xianjin 
Published: January 2022

Abstract
This article assumes that the elementary particle is a magnetic pole field formed by the interaction of positive and negative magnetic poles and believes that gravity, electromagnetic forces, strong forces and weak forces are all produced by the interaction of positive and negative magnetic poles. The collision of the high-energy elementary particles appears as a strong force, the decay of the high-energy elementary particles appears as a weak force, the cohesive force of the high-energy elementary particle magnetic pole field (the gravitational field) to its magnetic pole is gravity, and the spin force of the high-energy elementary particle magnetic pole field in the external field (the gravitational field) is the electromagnetic force. This article discusses a high-energy proton-antiproton collision experiment based on the interaction of positive and negative magnetic poles and reveals the production mechanism of protonium, tauium, muonium, positronium, three generations of leptons and neutrinos, and the final state. This article explains the unification of the strong force, weak force, electromagnetic force and gravity with unified phase field theory and tests this theory by the ATLAS and CMS experimental data at the LHC. The data of the ATLAS and CMS experiments at the LHC are completely consistent with the calculated data of the phase field curvature tensor equation. Differential geometric variables are covariant with physical variables. The Lagrangian function of Einstein's mass-energy equation, the Lagrangian function of the Schrodinger particle differential motion wave function based on the theory of relativity, the Lagrangian density of the Young-Mills gauge field equation, and the planet phase difference momentum-energy tensor of the curvature tensor equation are completely consistent in the high-energy proton-antiproton collision experiment. These results fully prove that the unified phase field theory is more in line with the physical reality of the high-energy proton-antiproton collision experiment.