bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL1 Pathway in HPV-Negative HNSCC Cells Is an Indicator of Radioresistance After Photon and Carbon Ion Irradiation Without Functional Involvement
Authors: Tiwari Dinesh Kumar , Hannen Ricarda , Unger Kristian , Kohl Sibylla , Heß Julia , Lauber Kirsten , Subtil Florentine S. B. , Dikomey Ekkehard , Engenhart-Cabillic Rita , Schötz Ulrike 
Published: April 2022

BackgroundTreatment of locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC) with photon radiation is the standard of care but shows only moderate success. Alterations in response toward DNA DSB repair, apoptosis, and senescence are underlying determinants of radioresistance in the tumor cells. Recently, senescence and the associated secretory phenotype (SASP) came into the focus of research and raised the need to identify the tumor-promoting molecular mechanisms of the SASP. The aim of this project was to unravel more of this process and to understand the impact of the IL1 pathway, which plays a major role in SASP. The studies were performed for photon and 12C-ion irradiation, which strongly vary in their effect on radioresistance.Materials and MethodsA panel of five HPV-negative HNSCC cell lines was treated with photon and 12C-ion irradiation and examined for clonogenic survival, DNA DSB repair, and senescence. SASP and IL1 gene expressions were determined by RNA sequencing and activation of the IL1 pathway by ELISA. A functional impact of IL1A and IL1B was examined by specific siRNA knockdown.ResultsCell killing and residual DSBs were higher after 12C-ion than after photon irradiation. 12C-ion induced more senescence with a significant correlation with cell survival. The impact on radioresistance appears to be less than after photon irradiation. The expression of SASP-related genes and the IL1 pathway are strongly induced by both types of irradiation and correlate with radioresistance and senescence, especially IL1A and IL1B which exhibit excellent associations. Surprisingly, knockdown of IL1A and IL1B revealed that the IL1 pathway is functionally not involved in radioresistance, DSB repair, or induction of senescence.ConclusionsIL1A and IL1B are excellent indicators of cellular radioresistance and senescence in HNSCC cells without functional involvement in these processes. Clearly more research is needed to understand the molecular mechanisms of senescence and SASP and its impact on radioresistance.
Distant Metastasis Pattern and Prognostic Prediction Model of Colorectal Cancer Patients Based on Big Data Mining
Authors: Liu Chuan , Wang Ting , Yang Jiahui , Zhang Jixiang , Wei Shuchun , Guo Yingyun , Yu Rong , Tan Zongbiao , Wang Shuo , Dong Weiguo 
Published: April 2022

AimsThis study aimed to investigate the distant metastasis pattern from newly diagnosed colorectal cancer (CRC) and also construct and validate a prognostic nomogram to predict both overall survival (OS) and cancer-specific survival (CSS) of CRC patients with distant metastases.MethodsPrimary CRC patients who were initially diagnosed from 2010 to 2016 in the SEER database were included in the analysis. The independent risk factors affecting the OS, CSS, all-cause mortality, and CRC-specific mortality of the patients were screened by the Cox regression and Fine–Gray competitive risk model. The nomogram models were constructed to predict the OS and CSS of the patients. The reliability and accuracy of the prediction model were evaluated by consistency index (C-index) and calibration curve. The gene chip GSE41258 was downloaded from the GEO database, and differentially expressed genes (DEGs) were screened by the GEO2R online tool (p &lt; 0.05, |logFC|&gt;1.5). The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway and Gene Ontology (GO) annotation and String website were used for enrichment analysis and protein–protein interaction (PPI) analysis of DEGs, respectively, and Cytoscape software was used to construct PPI network and screen function modules and hub genes.ResultsA total of 57,835 CRC patients, including 47,823 without distant metastases and 10,012 (17.31%) with metastases, were identified. Older age, unmarried status, poorly differentiated or undifferentiated grade, right colon site, larger tumor size, N2 stage, more metastatic sites, and elevated carcinoembryonic antigen (CEA) might lead to poorer prognosis (all p &lt; 0.01). The independent risk factors of OS and CSS were included to construct a prognosis prediction model for predicting OS and CSS in CRC patients with distant metastasis. C-index and calibration curve of the training group and validation group showed that the models had acceptable predictive performance and high calibration degree. Furthermore, by comparing CRC tissues with and without liver metastasis, 158 DEGs and top 10 hub genes were screened. Hub genes were mainly concentrated in liver function and coagulation function.ConclusionThe big data in the public database were counted and transformed into a prognostic evaluation tool that could be applied to the clinic, which has certain clinical significance for the formulation of the treatment plan and prognostic evaluation of CRC patients with distant metastasis.
DNA Hypermethylation-Regulated CX3CL1 Reducing T Cell Infiltration Indicates Poor Prognosis in Wilms Tumour
Authors: Mi Tao , Jin Liming , Zhang Zhaoxia , Wang Jinkui , Li Mujie , Zhanghuang Chenghao , Tan Xiaojun , Wang Zhang , Tian Xiaomao , Xiang Bin , He Dawei 
Published: April 2022

ObjectiveTo investigate the role of chemokines in Wilms tumours, especially their chemotaxis to immune cells and the role of DNA methylation in regulating the expression level of chemokines.MethodsRNAseqV2 gene expression and clinical data were downloaded from the TARGET database. DNA methylation data were downloaded from the GEO and cBioPortal database. The difference analysis and Kaplan-Meier(KM) analysis of chemokines were performed by edgeR package. Then predictive model based on chemokines was constructed by lasso regression and multivariate COX regression. ROC curve, DCA curve, Calibration curve, and Nomogram were used to evaluate the prognostic model. MCPcounter and Cibersort algorithm was used to calculate the infiltration of immune cells in Wilms tumour and para-tumour samples. Then the difference analysis of the immune cells was performed. The relationship between chemokines and immune cells were calculated by Pearson correlation. In addition, DNA methylation differences between Wilms tumour and para-tumour samples was performed. The correlation between DNA methylation and mRNA expression was calculated by Pearson correlation. Western blot(WB)and immunofluorescence were used to confirm the differential expression of CX3CL1 and T cells, and the correlation between them.ResultsA total of 16 chemokines were differentially expressed in tumour and para-tumour samples. A total of seven chemokines were associated with survival. CCL2 and CX3CL1 were positively correlated with prognosis, while high expression of CCL3, CCL8, CCL15, CCL18 and CXCL9 predicted poor prognosis. By lasso regression and multivariate COX regression, CCL3, CCL15, CXCL9 and CX3CL1 were finally included to construct a prediction model. The model shows good prediction ability. MCPcounter and Cibersort algorithm both showed that T cells were higher in para-tumour tissues than cancer tissues. Correlation analysis showed that CX3CL1 had a strong correlation with T cells. These were verified by Weston blot and immunofluorescence. DNA methylation analysis showed that various chemokines were different in para-tumours and tumours. CX3CL1 was hypermethylated in tumours, and the degree of methylation was negatively correlated with mRNA expression.Conclusion1. There is low T cell infiltration in nephroblastoma. 2. Chemokines such as CX3CL1 indicate a favourable prognosis and positively correlate with the number of T cells. 3. chemokines such as CX3CL1 are negatively regulated by DNA hypermethylation.
Microsimulation Model for Prevention and Intervention of Coloretal Cancer in China (MIMIC-CRC): Development, Calibration, Validation, and Application
Authors: Lu Bin , Wang Le , Lu Ming , Zhang Yuhan , Cai Jie , Luo Chenyu , Chen Hongda , Dai Min 
Published: April 2022

IntroductionA microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China.MethodsWe comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model’s external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies.ResultsWe found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening.ConclusionsThe well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention.
Knockdown of a Cyclic Nucleotide-Gated Ion Channel Impairs Locomotor Activity and Recovery From Hypoxia in Adult Drosophila melanogaster
Authors: Qiu Shuang , Xiao Chengfeng , Robertson R. Meldrum 
Published: April 2022

Cyclic guanosine monophosphate (cGMP) modulates the speed of recovery from anoxia in adult Drosophila and mediates hypoxia-related behaviors in larvae. Cyclic nucleotide-gated channels (CNG) and cGMP-activated protein kinase (PKG) are two cGMP downstream targets. PKG is involved in behavioral tolerance to hypoxia and anoxia in adults, however little is known about a role for CNG channels. We used a CNGL (CNG-like) mutant with reduced CNGL transcripts to investigate the contribution of CNGL to the hypoxia response. CNGL mutants had reduced locomotor activity under normoxia. A shorter distance travelled in a standard locomotor assay was due to a slower walking speed and more frequent stops. In control flies, hypoxia immediately reduced path length per minute. Flies took 30–40 min in normoxia for &gt;90% recovery of path length per minute from 15 min hypoxia. CNGL mutants had impaired recovery from hypoxia; 40 min for ∼10% recovery of walking speed. The effects of CNGL mutation on locomotor activity and recovery from hypoxia were recapitulated by pan-neuronal CNGL knockdown. Genetic manipulation to increase cGMP in the CNGL mutants increased locomotor activity under normoxia and eliminated the impairment of recovery from hypoxia. We conclude that CNGL channels and cGMP signaling are involved in the control of locomotor activity and the hypoxic response of adult Drosophila.
The Gut Microbiota in Liver Transplantation Recipients During the Perioperative Period
Authors: Lai Zhiyong , Chen Zongkun , Zhang Anhong , Niu Zhiqiang , Cheng Meng , Huo Chenda , Xu Jun 
Published: April 2022

Background: Chronic liver disease is a global problem, and an increasing number of patients receive a liver transplant yearly. The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients during the perioperative.Methods: We studied gut fecal microbial community signatures in 37 Chinese adults using 16S rRNA sequencing targeting V3-V4 hypervariable regions, with a total of 69 fecal samples. We analyzed the Alpha and Beta diversities of various groups. Then we compared the abundance of bacteria in groups at the phylum, family, and genus levels.Results: The healthy gut microbiota predominantly consisted of the phyla Firmicutes and Bacteroidestes, followed by Proteobacteria and Actinobacteria. Compared with healthy people, due to the dominant bacteria in patients with chronic liver disease losing their advantages in the gut, the antagonistic effect on the inferior bacteria was reduced. The inferior bacteria multiplied in large numbers during this process. Some of these significant changes were observed in bacterial species belonging to Enterococcus, Klebsiella, and Enterobacter, which increased in patients’ intestines. There were low abundances of signature genes such as Bacteroides, Prevotella, and Ruminococcus. Blautia and Bifidobacterium (considered probiotics) almost disappeared after liver transplantation.Conclusion: There is an altered microbial composition in liver transplantation patients and a distinct signature of microbiota associated with the perioperative period.
Mechanical Affective Touch Therapy for Anxiety Disorders: Feasibility, Clinical Outcomes, and Electroencephalography Biomarkers From an Open-Label Trial
Authors: Carpenter Linda L. , Kronenberg Eugenia F. , Tirrell Eric , Kokdere Fatih , Beck Quincy M. , Temereanca Simona , Fukuda Andrew M. , Garikapati Sahithi , Hagberg Sean 
Published: April 2022

BackgroundMost external peripheral nerve stimulation devices designed to alter mood states use electrical energy, but mechanical stimulation for activation of somatosensory pathways may be harnessed for potential therapeutic neuromodulation. A novel investigational device for Mechanical Affective Touch Therapy (MATT) was created to stimulate C-tactile fibers through gentle vibrations delivered by piezoelectric actuators on the bilateral mastoid processes.Methods22 adults with anxiety disorders and at least moderate anxiety symptom severity enrolled in an open-label pilot trial that involved MATT self-administration using a simple headset at home at least twice per day for 4 weeks. Resting EEG data were acquired before and after a baseline MATT session and again before the final MATT session. Self-report measures of mood and anxiety were collected at baseline, week 2, and week 4, while interoception was assessed pre- and post-treatment.ResultsAnxiety and depressive symptoms improved significantly from baseline to endpoint, and mindfulness was enhanced. EEG metrics confirmed an association between acute MATT stimulation and oscillatory power in alpha and theta bands; symptom changes correlated with changes in some metrics.ConclusionOpen-label data suggest MATT is a promising non-invasive therapeutic approach to anxiety disorders that warrants further development.
Medical Expulsive Therapy (MET) for Ureteral Calculi in Children: Systematic Review and Meta-Analysis
Authors: Bacchus Michael W. , Locke Rachel A. , Kwenda Elizabeth P. , DeMarco Romano T. , Grant Campbell , Bayne Christopher E. 
Published: April 2022

BackgroundMedical expulsive therapy (MET) is the use of medication to facilitate ureteral stone passage prior to surgical intervention. Practice guidelines for the use of MET in the pediatric population remain limited, primarily due to a scarcity of randomized controlled trials and concerns regarding dosing and side effects. To address this, we conducted a systematic review and meta-analysis to clarify the impact of MET on the spontaneous passage of pediatric stones located within the distal ureter.MethodsA narrow scope search using PubMed and Embase with a predefined search strategy was performed in September 2021 to identify all randomized controlled trials involving the use of pediatric MET for stones located in the distal ureter. Raw data from 6 eligible articles were extracted for pooled analysis. Our primary outcome was the overall effect of MET on ureteral calculi passage within 28 days compared to controls.ResultsThe mean age of patients in included studies was 7.6 years-old, with a range of ages 2–18 years old. In the pooled analysis of eligible studies, 235 patients received MET and 176 received placebo. The mean stone size was 6.40 mm in the treatment arm and 6.42 mm in the control arm. Children receiving MET were more likely than controls to experience spontaneous stone passage [Relative risk 1.39 (CI 95% 1.21–1.60)]. Considering all included studies, only one child treated with MET withdrew due to medication side effects.ConclusionOur systematic review and meta-analysis of the use of pediatric MET on spontaneous distal ureteral stone passage demonstrates a statistically significant benefit. The benefits of MET are diverse and include, possibly, minimizing exposure to anesthesia and radiation alongside improving surgical outcomes if ureteroscopy must be performed. Given the increasing incidence of ureteral stones in children and the nuances inherent to pediatric surgery due to smaller anatomy, MET represents an opportunity for safer and more effective pediatric stone management.
Comparing the Effects of a Pine (Pinus radiata D. Don) Bark Extract with a Quebracho (Schinopsis balansae Engl.) Extract on Methane Production and In Vitro Rumen Fermentation Parameters
Authors: Vera Nelson , Gutiérrez-Gómez Constanza , Williams Pamela , Allende Rodrigo , Fuentealba Cecilia , Ávila-Stagno Jorge 
Published: April 2022

The aim of this study was to compare the effects of a pine (Pinus radiata D. Don) bark extract (PBE) with a quebracho (Schinopsis balansae Engl.) extract (QTE) on methane (CH4) production and in vitro rumen fermentation parameters. A forage diet supplemented with PBE or QTE (0, 2 and 4% dry matter (DM) basis) was incubated for 24 h to determine in vitro DM disappearance (IVDMD), CH4, volatile fatty acids (VFA), and ammonia nitrogen (NH3-N) production. Differences were analyzed using Tukey’s test, orthogonal contrasts, hierarchical clustering heatmap (HCH), and principal component analysis (PCA). Both extracts (4% DM) decreased butyrate (Bu; p = 0.001), CH4 (p = 0.005), total VFA (p < 0.001), and NH3-N (p = 0.006) production and increased acetate (Ac; p = 0.003) without affecting the partitioning factor (p = 0.095). Propionate (Pr; p = 0.016) was increased, whereas IVDMD (p = 0.041) was decreased with QTE (4% DM). The inclusion of QTE (2% DM) decreased CH4 production (p = 0.005) and the (Ac + Bu)/Pr ratio (p = 0.003), whereas PBE (2% DM) decreased the NH3-N (p = 0.006) and total VFA production (p < 0.001). The HCH and PCA indicate a negative correlation (r = −0.93; p < 0.001) between CH4 production and tannins. In conclusion, PBE shares many of the effects generated by QTE on ruminal fermentation, although the magnitude of these effects depends on concentration. The PBE could be used as an additive in ruminant diets to reduce CH4 and NH3-N production without reducing IVDMD or increasing propionate, but further in vivo studies are required to clarify its effects on animal production.
Limitation of parasitic absorption in designs of three-state terahertz quantum cascade lasers with direct-phonon injection
Authors: Wang Li , Lin Tsung-Tse , Wang Ke , Hirayama Hideki 
Published: April 2022

Abstract
To maximize the population inversion in terahertz quantum cascade lasers for high-temperature operation, the scheme of electron injection following direct-phonon emission is more attractive than the common way via resonant tunneling. If this direct-phonon injection can be realized within a simple quantum structure (only three quantum states), much higher optical gain is expected even at room temperature. However, the attempts of this design in experiments are full of challenges. In this work, the non-equilibrium Green’s function method is introduced to draw a full picture of the quantum transport in this design. It demonstrates that the optical gain is strictly limited by a parasitic absorption from one specific high-lying state. Moreover, a strategy is proposed to avoid this limitation.
Analisis Perbedaan Beta Pada Perusahaan Perbankan Dan Perusahaan Manufaktur
Authors: Permatasari Anita 
Published: April 2022

Pasar modal memiliki peranan penting dalam menunjang perekonomian, sehingga sering kali pasar modal dapat dijumpai di banyak negara. Dengan kondisi pasar saham maupun perekonomian yang selalu berubah-ubah, menyebabkan ketidakpastian bagi investor untuk mendapatkan keuntungan, sehingga hampir semua investasi mengandung risiko. Risiko yang disebabkan disebabkan oleh pergerakan pasar agregat, dimana saham bergerak tergantung dari pergerakan pasar, yang dikenal dengan istilah Beta (β). Beta dapat diuji dengan menggunakan model Capital Asset Pricing Model (CAPM). Pada model Capital Asset Pricing Model, beta diartikan sebagai pengukur volatilitas return suatu sekuritas terhadap return pasar. Oleh karena itu sebelum melakukan investasi investor harus selalu memperhatikan dan mempertimbangkan faktor-faktor apa saja yang dapat mempengaruhi besarnya risiko yang ditanggungnya. Salah satu faktor yang harus diperhatikan dan dipertimbangkan oleh investor adalah tingkat suku bunga deposito. Mengingat industri perbankan juga sangat mempengaruhi perkembangan ekonomi suatu negara dan hampir seluruh transaksi ekonomi selalu berhubungan dengan bank. Penelitian ini mencoba untuk menganalisis perbedaan risiko-risiko sistematis pada perusahaan perbankan dan perusahaan manufaktur: uji validasi Capital Asset Pricing Model di Indonesia periode 2003 - 2006. Hasil penelitian ini menunjukkan bahwa terdapat pengaruh antara excess return pasar terhadap excess return individual pada perusahaan perbankan dan perusahaan manufaktur, sedangkan excess suku bunga deposito,baik excess suku bunga deposito 3 bulanan dan excess suku bunga deposito 6 bulanan tidak memiliki pengaruh terhadap access return individual, baik pada perusahaan perbankan maupun pada perusahaan manufaktur. Hasil kedua dari penelitian ini adalah tidak terdapat perbedaan antara beta excess return pasar, beta excess suku bunga deposito 3 bulanan dan beta excess suku bunga deposito 6 bulanan, baik pada perusahaan perbankan dan perusahaan manufaktur. Selain itu hasil penelitian ini juga menyebutkan Capital Asset Pricing Model pada perusahaan manufaktur lebih valid bila dibandingkan dengan Capital Asset Pricing Model pada perusahaan perbankan.
Analisis Segmentasi, Targeting Dan Positioning Melalui Program Siaran Pada Radio Mitra Batu
Authors: Agustim Warter 
Published: April 2022

This research was caused by the changing environment and other supporting factors. The changing of business pattern of seller market to buyer market made a company has to adapt their need and changing behaviour. By having this base a company need to do market segmenting, targeting, and positioning with broadcast program in order to serve customers having different characteristics. This research aimed to find out how to apply segmenting, targeting dan positioning (STP) in Mitra 97.0 FM Radio of Batu City in determining the marketing strategy by considering STP. This research used also descriptive method drawing the execution of STP and the lack of the company in implementing STP. Form the analysis result done, Mitra 97.0 FM Radio of Batu City tried to serve the large market and divide its customers (listeners) in several segmenting variables. The applied marketing strategy was by developing products and promoting sales by personal selling, publishing, and advertising. In executing this strategy Mitra FM Radio of Batu hoped that it could be a radio having incisive segments and advertising media for products agree with the customers (listeners) segment concerned.