bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping
Authors: Lee Hee Seung , Han Dai Hoon , Cho Kyungjoo , Park Soo Been , Kim Chanyang , Leem Galam , Jung Dawoon E. , Kwon Soon Sung , Kim Chul Hoon , Jo Jung Hyun , Lee Hye Won , Song Si Young , Park Jun Yong
Published: March 2022

As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. However, there are no truly representative models of ICC subtypes for use in studying developmental differences, carcinogenesis, and personalized drug response. Here, we sought to develop ICC organoid models that reflect the phenotypic, molecular and genetic properties of the parent tumor, and performed integrative clustering of multiple genomic data—with subtype analysis—using these models. ICC organoids from 17 patients pathologically diagnosed with cholangiocarcinoma were prepared according to a previously established organoid culture protocol. ICC patients were subclassified into small-duct (SD) type and large-duct (LD) type according to histological characteristics and S100P, N-cadherin, and CD56 expression. ICC organoids were successfully established within one month and exhibited a morphology similar to that of their matching primary cancer. LD- and SD-type organoids exhibited histologic phenotypes and staining patterns characteristic of the corresponding ICC subtypes. ICC organoids showed high concordance of somatic mutations with primary tumors. Unsupervised principal component analysis clustering effectively separated each type of ICC. Differential gene expression revealed significant enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type ICC (P < 0.05). Gene set enrichment analysis further demonstrated that the cholangiocarcinoma class 2 signature, defined by Andersen et al., was significantly enriched in the LD-type (enrichment score = 2.19, P < 0.001). A protein-protein interaction network analysis identified ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We successfully performed prospective modeling of histological subtype specification using patient-derived ICC organoids. Moreover, gene expression profiling of ICC organoids enabled identification of type-specific targetable pathways.
LMNA R527C mutation causes an inflammation driven progeria via triggering DNA-sensing pathways
Authors: Zhao Yingchi , Shu Wei , Liu Xiaoyu , Jiao Xuyao , Li Jianshuang , Liu Tao , Kuang Ming , Li Ridong , Du Hongqiang , Zhang Zeming , Zhou Zhe , Guo Xuefei , Wei Xuemei , Wang Dandan , Liu Tongtong , Li Yunfei , Liu Shengde , Chen Jingxuan , Luo Yujie , Xia Huawei , Cao Lili , Tian Wenmin , Sun Xue , Dong Wei , Zhou Guangqian , Gao Xiang , Zhou Qinghua , You Fuping
Published: March 2022

Homozygous mutations in Ig-like domain of LMNA cause severe progeria. Unlike typical HGPS mediated by progerin due to LMNAWT/G608G mutation, it remains elusive how these homozygous mutations cause progeria. We here found that patients with LMNAR527C/R527C mutation developed an atypical progeria with autoimmune symptoms. Compare to LMNAWT/G608G mutation, this mutation led to more severe inflammation in patients. MSCs from LMNAR527C/R527C patients exhibited overt inflammation and cellular senescence. Mechanistically, LMNAR527C/R527C mutation attenuated its binding to DNA binding protein BAF, which led to aberrant aggregation of Lamin A and activation of DNA sensing pathways. Inhibition of DNA sensors, cGAS or AIM2, can suppress inflammation and rescue the senescence of patient-derived MSCs. LmnaR527C/R527C mice showed enhanced inflammation, and developed accelerated aging and dead at an early age after high-fat diet (HFD) feeding, which could be rescued by deficiency of AIM2 or treatment by a small molecule inhibitor of cGAS-STING. Therefore, we demonstrated that LMNAR527C/R527C mutation damped its interaction with DNA-binding proteins and exposed damaged DNA to the cytosolic DNA sensors, which triggered aberrant inflammatory responses and promoted the onset of accelerated aging. The present study uncovered that an inflammation driven progeria was caused by LMNA mutation and DNA sensing pathways could be potential therapeutic targets for progeria syndromes caused by homozygous mutations in Ig-like domain of LMNA.
CD3+CD4-CD8- Double-Negative Lymphocytes Are Increased In The Aqueous Humour Of Patients Affected By Retinitis Pigmentosa: Their Possible Role In Mediating Inflammation
Authors: Bacherini Daniela , Maggi Laura , Sodi Andrea , Vannozzi Lorenzo , Mazzoni Alessio , Capone Manuela , Virgili Gianni , Falsini Benedetto , Cosmi Lorenzo , Rizzo Stanislao , Annunziato Francesco , Giansanti Fabrizio , Liotta Francesco
Published: March 2022

Background: Recently, evidence has arisen supporting a significant role for immune and oxidative mediated damage underlying the pathogenesis of different types of retinal diseases, including retinitis pigmentosa (RP). Our study aims to evaluate the possible presence of immune cells and mediators in patients affected by RP using flow cytometric analysis of the aqueous humour (AH).Methods: We recruited 12 patients affected by RP and 9 controls undergoing cataract surgery. All patients underwent a complete ophthalmological examination, fundus color photography, optical coherence tomography (OCT), Goldmann kinetic perimetry, electroretinographic and genetic tests. Flow cytometric analysis of of peripheral blood (PB) and AH samples provided a membrane staining which targeted surface molecules (CD14, CD16, CD19, CD3 and CD4, CD8, CD161) identifying monocytes, natural killer (NK), B, T cells, and T subpopulations respectively. Moreover, lymphocytes were polyclonally stimulated to evaluate cytokine (CK) production at single cell level.Results: The circulating immune-cell distribution was comparable between RP patients and controls. Conversely, in the AH of controls we could detect no cells, while in the RP AH samples we found infiltrating leucocytes, consisting of T (CD3+), B (CD19+), NK (CD16+CD3-) cells and monocytes (CD14+). In the RP patients the frequency of most infiltrating cell populations was substantially comparable between the AH and PB, while among T subpopulations, the frequency of CD3+CD4+ T cells was significantly reduced in the RP AH compared to PB, and CD3+CD4-CD8- double-negative (DN) T cells resulted markedly and significantly increased in the RP AH. The analysis of the cytokine production showed a trend towards an increased frequency of CD3+CD8-CD161+IFNgamma-producing cells and a decrease of CD3+CD8+IL-4-producing cells in the RP AH.Conclusions: The detection of immune cells in the AH of patients with RP is consistent with the hypothesis of an immune-mediated pathogenesis of the disease. The presence of CD3+CD4-CD8- DN T cells and of a Th1-skewed phenotype in the AH could be related to a potential involvement of immune-mediated and inflammatory mechanisms in the disease. A better understanding of the fundamental features of inflammation pathways will provide significant insights in the pathogenesis of RP, and a possible avenue toward new therapeutic approaches.
Vascular Calcification in Different Arterial Beds in Ex Vivo Ring Culture and in Vivo Rat Model
Authors: Muyor Karen , Laget Jonas , Cortijo Irene , Duranton Flore , Jover Bernard , Argilés Àngel , Gayrard Nathalie
Published: March 2022

Background.Vascular calcification is a risk factor for cardiovascular and kidney diseases. Medial calcification may differently affect the arterial tree depending on vessel location and smooth muscle injury. Objective.The aim was to map the anatomical distribution of vascular calcifications on different arteries and artery locations, in cultured artery rings (ex vivo) and in a rat model of elastocalcinosis (in vivo).Design and Results. Vascular calcification was assessed histologically (von Kossa staining of the media) and by calcium content measurement. Arteries of different sizes were harvested from untreated rats for ring culture and from the vitamin D3-nicotine (VDN) rat model for direct observation. When cultured in pro-calcifying conditions, thoracic aorta exhibited similar calcification from the arch to the diaphragm. Calcification increased in abdominal aorta along with the reduction in cross sectional area. Carotid and renal arteries exhibited similar ex vivo calcification. In VDN rats, calcification was greater in carotid artery than in aorta, and was accompanied by fibrosis and apoptosis. Ex vivo, calcification was increased by the induction of lesions on arteries.Conclusions.Along the vascular tree, calcification of the arterial wall increases with the narrowing of vessels in ex vivo ring culture and in vivo. The observed differences represent local susceptibility of the vessels to the calcifying processes.
Qingfei Tongluo formula mitigates Mycoplasma pneumoniae infection via PERK signaling pathway
Authors: Liu Xiuxiu , Wang Mingjing , Kan Qianna , Lin Yan , Jiang Zhiyan
Published: March 2022

Introduction: Mycoplasma pneumoniae pneumonia (MPP) is usually found in school-aged children and seems to relapse easily because of the resistance to antibiotics. Qingfei Tongluo formula (QTF) is clinical used Traditional Chinese Medicine to treat MPP. Our previous study demonstrated that QTF exhibited ameliorative effects on experimental MPP mice model. In this study, we tried to further explore the function and underlying mechanism of QTF in MPP. Methods: MP was applied to infect A549 cells and BALB/c mice to mimic MPP in vitro and in vivo. Cytokine release and reactive oxygen species (ROS) production were analyzed using Enzyme-linked immunosorbent assay (ELISA) assay and flow cytometry. Western blot analysis was used to detect the protein involved in endoplasmic reticulum (ER) stress. Results: We found that MP infection enhanced cytokine release and ER stress in vitro and in vivo, and these effects could be alleviated by QTF. Moreover, protein kinase RNA-like endoplasmic reticulum kinase (PERK) knockdown alleviated MP infection-induced cytokine release, ROS production, and ER stress in A549 cells. While PERK overexpression exhibited the opposite effects. Conclusions: QTF alleviated MP infection-induced cytokine release, ROS production, and ER stress via inhibiting PERK signaling pathway.
C2orf40 inhibits Metastasis and Regulates Chemo-resistance and Radio-resistance of Nasopharyngeal Carcinoma Cells by Influencing Cell Cycle and Activating the PI3K/AKT/mTOR Signaling Pathway
Authors: Xie Zuozhong , Li Wei , Ai Jingang , Xie Jun , Zhang Xiaowei
Published: March 2022

Background：Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in Southern China. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the roles of C2orf40 in nasopharyngeal carcinoma has not been studied.Methods：In this study, a bioinformatics analysis was performed to identify the differentially expressed genes in NPC. The quantitative methylation levels was detected using pyrosequencing. qRT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to detect the expression level of related RNA and proteins. Cell proliferation was detected using CCK-8 assay, and colony formation capability was detected using colony formation.assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. The apoptosis level of cells was assessed using TUNEL staining. Endogenous DNA damage and repair were assessed by the comet assay . Cell cycle analyses carried out by flow cytometry. Finally, We used a xenograft nude mouse to verify the roles of C2orf40 in chemoresistance and radioresistance in vivo.Results：We found that the C2orf40 expression was significantly downregulated in NPC tissues and inversely associated with a poor prognosis. In vivo and in vitro functional experiments confirmed that overexpression of C2orf40 significantly inhibited the migration and invasion of NPC cells, and promoted their sensitivity to radiotherapy and chemotherapy of NPC cells. Mechanically, the expression level of C2orf40 was negatively correlated with the expression levels of CCNE1 and CDK1. Overexpression of C2orf40 induced cell cycle arrest of NPC cells at G/M phase. In addition, C2orf40 can down-regulated the expression levels of homologous recombination-related proteins (BRCA1, BRCA2, RAD51, and CDC25A) and inhibited the activity of the PI3K/AKT/mTOR signaling pathway.Conclusion：The results clarified the biological functions and mechanisms of C2orf40, as a tumor suppressor gene, in NPC, and provided a potential molecular target for improving the sensitivity of NPC to radiotherapy and chemotherapy.
Dynamics of invariant solutions of mKdV-ZK arising in a homogeneous magnetised plasma
Authors: Kumar Raj , Verma Ravi Shankar
Published: March 2022

Classical Lie symmetry analysis is proposed to get similarity reductions of a nonlinear (3+1)-modified Korteweg de Vries-Zakharov-Kuznetsov equation. The equation is often used to control the type of weakly nonlinear ion-acoustic waves in a homogeneous magnetised electron-positron plasma. In a magnetised plasma including some hot and cold ions, such waves exist. Some more general types of analytical solutions to the equation are derived in this article. Through their animation profiles, the dynamics of electrostatic potential indicate elastic single soliton to multi solitons, elastic multi solitons, kink to stationary, bell-shaped to asymptotic. The solutions are confirmed by comparing the existing results.
Bioinformatics analysis of potential core genes for pilocytic astrocytoma
Authors: zhang siqi , Zeng Hongwu
Published: March 2022

Background
Pilocytic astrocytoma (PA) is the most common primary brain tumor of childhood. Due to its complicated pathogenesis, the choice and timing of adjuvant therapy after tumor treatment are controversial. This study explored and identified potential biomarkers for PA.
Materials and methods
To identify potential core genes in PA that may provide new therapeutic insights, we analyzed three gene chips (GSE50161, GSE66354, GSE86574) screened from the GEO database. Differentially expressed genes (DEG) from the tissues of PA and normal brain were screened using GEO2R. To determine the functional annotation and pathway of DEG, Gene Ontology (GO) and KEGG pathway enrichment analysis were conducted using DAVID database. Protein interactions of DEG were visualized using PPI network on Cytoscape software. Next, 10 Hub nodes were screened from the differentially expressed network using DMNC algorithm on CytoHubba software and subsequently identified as Hub genes. Finally, the relationship between Hub genes and the prognosis of PA patients was described using GEPIA2 survival analysis web tool.
Results
A total of 37 up-regulated and 144 down-regulated genes were identified through microarray analysis. Amongst the 10 Hub genes selected, SLC12A5 and RAB3C are associated with poor prognosis in a Pilocytic astrocytoma based on the survival analysis.
Conclusion
Our study suggests that low expression of SLC12A5 and RAB3C are associated with poor prognosis in PA patients, whether they can be used as a new therapeutic target for PA.
Bayesian Updating of Seismic Fragility Curves Through Experimental Tests
Authors: Tekeste Gidewon Goitom , Correia António A. , Costa Aníbal G.
Published: March 2022

Fragility curves, commonly derived using analytical methods, are important ingredients of seismic risk analysis of structures in the framework of performance-based earthquake engineering. Hence, the accurate estimation of realistic fragility functions is a decisive step in a reliable risk assessment. This paper proposes a Bayesian updating procedure applied to analytical fragility curves of reinforced concrete (RC) structures based on data from experimental tests, namely shaking table tests. The latter are commonly performed by progressively increasing the intensity of the input motion applied to the same test specimen. In this regard, the maximal benefit from the output of a shaking table test is sought here, aiming to convert n sequential stages of a shaking table test of a single virgin specimen into n equivalent shaking table tests that are performed on n virgin specimens. This is performed by modifying the intensity of the input motion applied during the stage-wise testing based on a damage index coefficient. The parametric studies performed to validate this objective reveal that the approach is more suitable for simple structures compared to large or complex structures. The ATC-58 and Markov Chain Monte Carlo (MCMC) approaches for Bayesian updating of fragility curves are also closely examined and compared. The proposed Bayesian updating is applied to a RC structure, where fragility curves that are derived from incremental dynamic analysis are updated using shaking table results. The updating is examined considering three damage state models, namely HAZUS, homogenized RC and strain-based damages states. This work also highlights the pitfalls of using a limited sample of experimental test data for updating less reliable priors. Besides, the MCMC-based approach is shown to be more robust in the presence of complex analytical fragilities than the ATC-58 approach.
Variations in the poly-histidine repeat motif of HOXA1 predispose individuals to bicuspid aortic valve
Authors: Odelin Gaëlle , Faucherre Adèle , Marchese Damien , Pinard Amelie , Faure Emilie , Herbane Marine , Théron Alexis , Avierinos Jean-François , Jopling Chris , Collod-Béroud Gwenaelle , Rezsohazy René , Zaffran Stephane
Published: March 2022

Bicuspid aortic valve (BAV) is the most common cardiovascular malformation (0.5–1.2% of the population) and is often associated with premature aortic valve stenosis or insufficiency, aortic aneurysm and other congenital cardiac heart defects. Although highly heritable, few causal mutations have been identified in BAV patients. Here, we report the association of novel variants in the transcription factor HOXA1 with BAV in humans. Targeted sequencing of HOXA1 in a cohort of 333 BAV patients identified rare indel variants in the homopolymeric histidine tract of HOXA1. In vitro analysis revealed that disruption of the histidine repeat motif causes a significant reduction in the half-life of the protein, and that these variants are associated with a defective transcriptional activity of the HOXA1 protein. Targeting the zebrafish hoxa1a ortholog in vivo resulted in aortic valve defects that could be rescued by expressing the wild-type human HOXA1. Furthermore, expression of HOXA1 Histidine variants in zebrafish also impacted aortic valve development indicating a dominant negative effect of these mutated proteins. Lastly, homozygous knockout mice for Hoxa1 develop a BAV phenotype, which is associated with a very small, rudimentary non-coronary leaflet. Genetic lineage analysis indicates that this defect is caused by a strong reduction of mesenchymal cells in the intercalated cushion due to a failure of neural crest cell migration toward the heart which is consistent with our transcriptomic analysis showing a down-regulation of premigratory and migratory neural crest markers in Hoxa1−/− compared with control embryos. Together, these findings indicate that variants causing HOXA1 dysfunction play a significant role in the genetic cause of BAV in humans.
Impact of KRAS mutations on clinical outcomes of patients with advanced non-squamous non-small cell lung cancer receiving anti PD1/PDL1 therapy.
Authors: Veccia Antonello , Dipasquale Mariachiara , Kinspergher Stefania , Monteverdi Sara , Girlando Salvatore , Barbareschi Mattia , Caffo Orazio
Published: March 2022

PurposeTo evaluate the impact of KRAS mutations on response and survival outcomes in mutated vs wild type KRAS advanced non squamous non small cell lung cancer patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy. Patients and methodsWe retrospectively identified 119 patients, most of which (58%) were wild type. For each patient we evaluated overall survival (OS), progression free survival (PFS) and disease control rate (DCR). An exploratory analysis was performed among mutated patients to investigate the impact of specific KRAS mutations on response and survival outcomes. ResultsAfter a median follow-up of 10.3 months, the median OS was 14.9 months (95% CI 7.6 – 22.7) in wild type KRAS patients vs 14.7 months (95% CI 8.0 – 19.5) in mutated KRAS patients; p-value=0.529. No differences were also detected between two groups in terms of PFS and DCR. Patients with pG12C KRAS mutation reported survival and response outcomes that were not statistically different from those of patients with other KRAS mutations. ConclusionOur data confirmed that KRAS mutational status is not associated with survival and response outcomes in advanced non squamous NSCLC patients treated with immunotherapy alone or combined to chemotherapy.
Influence of Age on Long-term Net Survival Benefit for Early-stage MALT Lymphomas Treated With Radiotherapy: a SEER Database Analysis (2000-2015)
Authors: Wu Yunpeng , Liu Xin , Imber Brandon S. , Zhong Qiu-Zi , Yang Yong , Wu Tao , Chen Si-Ye , Chen Bo , Song Yong-Wen , Fang Hui , Jin Jing , Liu Yue-Ping , Jing Hao , Tang Yuan , Li Ning , Lu Ning-Ning , Wang Shu-Lian , Chen Fan , Yin Lin , Zhang Xi-Mei , Zhu Jingru , Tsang Richard , Yahalom Joachim , Hu Chen , Men Kuo , Deng Min , Xia Changfa , Li Ye-Xiong , Qi Shu-Nan
Published: March 2022

BACKGROUND Given the lower incidence of lymphoma-related death but higher background mortality in patients with early-stage mucosa-associated lymphoid tissue (MALT) lymphoma, it is critically important to examine how age affects a treatment’s survival benefit. METHODS 9,467 patients with early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Primary therapy was classified as radiotherapy (n = 3,407), chemotherapy (n = 1,294), and other/unknown treatments including observation (n = 4,766). Inverse probability of treatment weighting (IPTW) was conducted to balance baseline characteristics between groups. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were conducted to compare survival differences between treatment modalities by controlling for the background mortality. Radiotherapy–age interaction was examined.RESULTS Across age-groups, early-stage MALT lymphoma patients were at lower risk of lymphoma-related death than death due to other causes. The 10-year overall survival (OS, 73.8%) and RS (96.6%) rates were significantly higher, and the SMR (1.14) significantly lower, with radiotherapy than with chemotherapy (OS, 61.7%; RS, 86.4%; SMR, 1.54; P < 0.001) or other/unknown treatments (OS, 61.1%; RS, 87.2%; SMR, 1.41; P < 0.001). By multivariable analysis and IPTW, radiotherapy remained an independent predictor of better RS (HR 0.81, 95%CI, 0.73-0.89; P < 0.001). A significant interaction between age and radiotherapy was identified for both RS (Pinteraction = 0.016) and OS (Pinteraction = 0.024), indicating greater benefit in young adults.CONCLUSION Radiotherapy can provide significant survival benefit in early-stage MALT lymphoma, especially in young adults.
lncRNA C9orf139 can regulate the progression of esophageal squamous carcinoma by mediating the miR-661/HDAC11 axis
Authors: Yang Xiaojie , Shen Zhimin , Zhang Weiguang , Lin Yukang , Li Liming , Chai Tianci , Zhang Peipei , Kang Mingqiang , Lin Jiangbo
Published: March 2022

Background: Increasing evidence indicated that long non-coding RNAs (lncRNAs) play multiple functions in the development of cancer and function as indicator of diagnosis and prognosis. This study was to investigate the roles lncRNA C9ORF139 in the progression of esophageal squamous carcinoma (ESCC). Methods: RT-qPCR analysis was employed to evaluate mRNA expressions. Western blot was performed to measure relevant protein level. Colony formation and CCK-8 assays were conducted to certify proliferative ability. Cell apoptosis and migration were measured using Annexin V-FITC and Transwell assay respectively. The underlying mechanism of lncRNA C9orf139 was surveyed by luciferase activity reporter assay and further verified using tumor xenograft in vivo. Protein-protein interaction network was built using STRING database.Results: C9orf139 was highly expressed in ESCC and significantly suppressed cell proliferation, promoted apoptosis and inhibited migration and invasion. C9orf139 could negatively regulate miR-661 expression. While HDAC11 expression was negatively regulated by miR-661. C9orf139/miR-661/HDAC11 axis was further involved in regulating the expression of NF-κB signaling pathway. The association between the C9orf139 knockdown and the reduced tumor growth and size was observed in vivo study. Conclusion: C9orf139 is highly expressed in ESCC, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of ESCC progression is achieved by mediating the miR-661/HDAC11 axis.
Building capacity in quantitative research and data storytelling to enhance knowledge translation: a training curriculum for peer researchers
Authors: Tian Jason M. Lo Hog , Watson James R. , Deyman Megan , Tran Billy , Kerber Paul , Nanami Kajiko , Norris Deborah , Samson Kim , Cioppa Lynne , Murphy Michael , Mcgee A. , Ajiboye Monisola , Chambers Lori A. , Worthington Catherine , Rourke Sean B.
Published: March 2022

Background
Many community-based HIV research studies incorporate principles of greater involvement and meaningful engagement of people living with HIV (GIPA/MEPA) by training people with HIV as peer researchers. Unfortunately, there are still some aspects of research (e.g., quantitative data analysis and interpretation) where many projects fall short in realizing GIPA/MEPA principles. To address these gaps, we developed an eight-week training course that aimed to build capacity around the understanding and interpretation of quantitative data and incorporating lived experience to increase the impact of the knowledge transfer and exchange phase of a study.
Methods
Peer researchers (n = 8) participated from British Columbia, Alberta, and Ontario and lessons learned from the training were implemented throughout the dissemination of research findings from the People Living with HIV Stigma Index study. This paper presents the curriculum and main training components, course evaluation results, and challenges and lessons learned. The manuscript was created in collaboration with and includes the perspectives of both the peer researchers involved in the training, as well the course facilitators.
Results
Throughout the course, peer researchers’ self-assessed knowledge and understanding of quantitative research and data storytelling improved and, through interactive activities and practice, they gained the confidence to deliver a full research presentation. This improved their understanding of research findings, which was beneficial for discussing results with community partners and study participants. The peer researchers also agreed that learning about integrating lived experience with quantitative data has helped them to make research findings more relatable and convey key messages in a more meaningful way.
Conclusions
Our training curriculum provides a template for research teams to build capacity in areas of research where peer researchers and community members are less often engaged. In doing so, we continue to uphold the principles of GIPA/MEPA and enhance the translation of research knowledge in communities most greatly affected.
AMPK/ULK1 and JNK/p38/ERK Regulate Serotonin (5‐hydroxytryptamine) -induced Autophagy in Hepatoma Cells
Authors: Wang Chao , Wang Yang , Li Shulin , Cui Xinhua , Song Yuli , Tang Xudong , Xu Hongyue , Shi Jin yang ,   Yunxiao Ma1, Zhou Hong , An Yanan , Shen Keshu , Yu Lu
Published: March 2022

It has been reported that serotonin (5-hydroxytryptamine, 5‐HT), autophagy and ROS are involved in the pathogenesis of cancer, here, we used HepG2 and Hep3B cells as model cells to investigate whether 5-HT could induce hepatoma cells autophagy and its possible mechanisms involved in ROS. First, the immunofluorescence results showed that 5-HT could induce the production of LC3 in hepatoma cells, and western blot results showed that 5-HT induced a complete autophagy process in hepatoma cells. Secondly, our results showed that 5-HT induced autophagy through the AMPK/ULK1 instead of the mTOR-dependent pathway in hepatoma cells. Thirdly, 5-HT also could stimulate autophagy through JNK/p38/ERK pathway activation in hepatoma cells. Finally, the DHR 123 assay showed that 5-HT could induce ROS production in hepatoma cells and the ROS scavenger NAC significantly inhibited the 5-HT-induced LC3 in hepatoma cells, this showed that ROS was necessary for 5-HT-induced autophagy in hepatoma cells. Therefore, we demonstrated that 5-HT induced autophagy in hepatoma cells, which was mediated by respective AMPK/ULK1 and JNK/p38/ERK pathways not by inhibiting phosphorylation of the mTOR pathway, and ROS participated in the occurrence of 5-HT-induced autophagy. This provided a theoretical basis for the important effects of 5-HT in the treatment or prevention of cancer, and provided new ideas for the development of new anti-cancer drugs targeting 5-HT receptors.
Tunable Plasmonic Band-Pass Filter Using Five Circular Ring Resonators.
Authors: HamidAbbasi
Published: March 2022

This paper investigates and builds a highly sensitive refractive index sensor based on the resonance system in plasmonic structure. The proposed sensor structure consists of two waveguides and five loops. The results show that the resonance wavelength changes significantly with increasing refractive index, which proves that this method is suitable for understanding and analyzing the behavior of resonance wavelength and refractive index. In this research, we examine the characteristics of measurement such as sensitivity and quality factor and competency form (FOM). Compared to replicon sensors based on a similar structure, this proposed sensor can accept a more flexible amplitude of wavelength and a wider range of refractive index. As a result of this approach, it can be used in areas such as biochemical and medical analysis.
Identification of a 5-Gene-Based Signature to Predict Prognosis and Correlate Immunomodulators for Rectal Cancer
Authors: Lin Yi , Ji Qiang , Peng Yichen , Yu Chunna , Zheng Yi , Kang Xun , Zheng Jianwei , Bai Rixing , Yan Wenmao , Wang Xiaomin , Li Wenbin
Published: March 2022

Background
Specific tumour markers that are similar to the 21-gene assay in breast cancer, have yet to be identified in rectal cancer. The objective of this study is to identify a novel genetic signature in rectal cancer to help predict survival and provide clues for immunotherapy.
Methods
Differentially Expressed Genes were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the prognostic signature. Then, a nomogram was constructed to estimate survival predictability in both training and validation cohorts. Subsequently, we integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis to reveal potential functions and relevant mechanisms.
Results
A total of 468 DEGs were identified between rectal cancer and normal tissues, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected for further analyses in a prognostic model. According to the risk-score calculated by the model, results showed that overall survival was significantly worse in the high-risk group (P = 0.0044). The model exhibited high performance in time-dependent ROC as well as a nomogram. Notably, as an independent prognostic factor, the risk-score was associated with vascular invasion (P = 0.038). Furthermore, there was a dramatic difference in nonregulatory CD4 + and CD8 + T cells between the high and low-risk groups. Strikingly, the Heat map plot showed that genes in our model were correlated with immune inhibitors. Moreover, there was also a big difference in autophagy-, immune-, cell cycle-, infection-, and apoptosis-associated terms and pathways between high and low-risk groups by GO and KEGG enrichment. Then, hsa-miR-6887 was predicted to be a common microRNA of 5 genes, which was only correlated with GNG7 in expression. Markedly, the functional states of differentiation, apoptosis, and quiescence were highly related to the 5-gene signature in single-cell analysis.
Conclusion
Our results suggest that the 5-gene-based signature could serve as a novel prognostic biomarker in rectal cancer, which could be of benefit for decision-making in rectal cancer immunotherapy.
Vinpocetine restores cognitive and motor functions in Traumatic brain injury challenged rats
Authors: Deshmukh Rahul , Kajal Kajal
Published: March 2022

Traumatic brain damage is common worldwide and the treatments are not defined. Vinpocetine is PDE1 inhibitor and reported to protect brain damage following various neurptoxic insults. Here in the current study we have investigated the neuroprotective potential of vinpocetine against traumatic brain injury. TBI was induced by Marmarou weight drop method in rats. Brain damage was evaluated using cognition, motor functions and alterations in biomolecules. Injured rats were treated with different doses of vinpocetine for four weeks. Traumatic brain injury in rats produced significant deteriotation of cognition and motor functions. Elevation in markers of oxidative stress, alterations in other monoamines were observed in injured rats, whereas vinpocetine treated rats showed significant recovery with improved alterations in cognitive and motor functions and also restored traumatic brain injury induced biochemical alterations. The observed neuroprotective potential of vinpocetine could be related to its antioxidant potential and its ability to frestore brain neurohemical alterations under stressful conditions.
Pancreatic stones formation in the pancreatic stent after central pancreatectomy: A case report
Authors: Gai Ying-Wen , Wang Huai-Tao , Tan Xiao-Dong
Published: March 2022

BackgroundPancreatic stenting is a common method to prevent pancreatic anastomosis stricture and pancreatic fistula after pancreaticoduodenectomy, pancreatectomy, and other pancreatic surgeries. Since the decomposition and digestive ability of pancreatic juice is strong, there is reportedly a low risk of stone formation in the tube. Case presentationA 68-year old female patient who was diagnosed with a pancreatic space occupying lesion was admitted to our department. Central pancreatectomy was performed with the insertion of an internal pancreatic stent, and the patient recovered well postoperatively. However, she was hospitalized again 1 year later with complains of exudation from the abdominal incision. Detailed clinical, imaging, and laboratory examinations revealed multiple stones in the pancreatic stent, which was the major cause of a pancreatic pseudocyst and pancreatitis. During the operation, we anastomosed the cyst to the jejunum and inserted another pancreatic stent without fixation in case of an anastomosis stricture or recurrence of pancreatic stones occurs. The patient was discharged 7 days postoperatively and no other complications were reported during the patient’s follow-up visit half a year later.ConclusionWe described a rare case of postoperative pancreatic stent stones complicated by chronic pancreatitis and pancreatic pseudocyst after central pancreatectomy. Application of pancreatic stent should be carefully evaluated considering its potential complication presented in this report.
CPT-Based Liquefaction Resistance of Clean and Silty Sands: A Drainage conditions Based Approach
Authors: Ecemis Nurhan , Monkul Mehmet Murat , Tütüncü Yunus Emre , Arik Mustafa Sezer
Published: March 2022

The cone penetration test-based simplified liquefaction triggering evaluations are largely based on linking liquefaction manifestations in the field to cone penetration resistance. These relationships are interpreted in such a way that for given penetration resistance, the liquefaction resistance increases as non-plastic fines content (FC) increases. However, several studies have indicated discrepancies in this relationship. Hence, there is a lag in rational scientific understanding of this observation. In this study, an experimental research program was undertaken to investigate the CPT-based liquefaction assessment by considering the effects of drainage conditions on the relationship between CPT resistance and liquefaction resistance. First, clean sand and silty sands having 5, 15, and 35% FC were tested at different relative densities by stress-controlled cyclic direct simple shear (CDSS) tests to investigate cyclic resistance of silty sand with varying amounts of non-plastic fines. Then, a set of tests involving piezocone penetration (CPTu), seismic CPTu (SCPTu), and direct push permeability (DPPT) were undertaken in a large-scale box filled with the same soils used in the CDSS tests. The large-scale test results quantified the effect of drainage conditions (coefficient of consolidation) on cone penetration resistance. Finally, by combining the CDSS and CPTu test results, an alternative CPT-based liquefaction resistance relationship was proposed by considering the effects of drainage conditions.
Combination Treatment with Histone Deacetylase and Carbonic Anhydrase 9 Inhibitors Shows Therapeutic Potential in Experimental Diffuse Intrinsic Pontine Glioma
Authors: Fujita Naohide , Bondoc Andrew , Ishida Joji , Taccone Michael S. , Riemenshneider Alexandra , Luck Amanda , Srikant Dilakshan , Siddaway Robert , Kondo Akihide , Arai Hajime , Smith Christian , McDonald Paul , Hawkins Cynthia , Dedhar Shoukat , Rutka James
Published: March 2022

Purpose: Despite extensive research, an effective and safe treatment for diffuse intrinsic pontine glioma (DIPG) has not been established. In this study, we investigate the therapeutic potential of combination therapy with histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors against DIPG.Methods: We used RNA sequencing data from DIPG patient samples to evaluate the expression of the carbonic anhydrase family and the activity of the hypoxia signaling pathway. Next, we performed a synergy screen using CA9 inhibitor SLC-0111 and the HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. We selected the SLC-0111/HDACi combination showing the highest synergy, and its effects on cell proliferation, invasion, and migration were evaluated. We also measured changes in histone acetylation, apoptosis, cell cycle, and intracellular pH.Results: CA9 was significantly upregulated in human DIPG samples. Furthermore, pathways downstream of CA9 were found to be activated when compared to normal brain tissue. The synergy screen revealed that the combination of SLC-0111 and pyroxamide was most effective at inhibiting DIPG cell proliferation. Furthermore, this combination reduced cell migration and invasion potential while enhancing histone acetylation with subsequent reduction of cell population in S Phase. Finally, the SLC-0111 and pyroxamide combination showed greater reduction of intracellular pH as compared to each agent alone.Conclusion: Our in vitro data suggest that the combination of SLC-0111 and pyroxamide shows promise in the treatment of experimental DIPG. Based on these findings, further investigation of this combination therapy in preclinical models is warranted.
Paneth cell maturation is related to epigenetic modification during neonatal–weaning transition
Authors: Baba Ryoko , Kokubu Keiji , Nakamura Kenta , Fujita Mamoru , Morimoto Hiroyuki
Published: March 2022

Paneth cells are antimicrobial peptide-secreting epithelial cells located at the bottom of the intestinal crypts of Lieberkühn. Crypts begin to form around day 7 of postnatal mice (P7), and Paneth cells usually appear within the first 2 weeks. Paneth cell dysfunction has been reported to correlate with Crohn’s disease-like inflammation, showing narrow crypts or loss of crypt architecture in mice. The morphology of dysfunctional Paneth cells is similar to that of a Paneth/goblet intermediate cell. However, it remains unclear whether the formation of the crypt is related to the maturation of Paneth cells. In this study, we investigated the histological changes in the mouse ileum postnatally and assessed the effect of the methyltransferase inhibitor on epithelium development using organoid culture. The morphological and functional maturation of Paneth cells occurred in the first 2 weeks and was accompanied by histone H3 lysine 27 (H3K27) trimethylation. Inhibition of H3K27 trimethylation suppressed crypt formation and Paneth cell maturation on organoids derived from ileum of early second postnatal mouse. Overall, our data show that post-transcriptional modification of histones, particularly H3K27 trimethylation, leads to the structural and functional maturation of Paneth cells during postnatal development.
Private car or public transport? - what effects does the service accessibility have on public transport utilisation in the City of London
Authors: J Aleksandra
Published: March 2022

In recent years there have been an increased drive globally to reduce private car journeys and increase the public transport use, cycling or walking. To support the shift in behavioural change and enable transition to more sustainable transport choices, many researches have been carried out to identify factors that may influence commuters’ decisions in relation to their transport mode selection. Number of those have shown that good quality public transport services can lead to its improved attractiveness. This study examines public transport accessibility levels across the City of London and its effects on the public transport utilisation and car ownership in the city.
One-pot synthesis of Au-M@SiO2 (M = Rh, Pd, Ir, Pt) core-shell nanoparticles as highly efficient catalysts for the reduction of 4-nitrophenol
Authors: Hao Junfang , Liu Bin , Maenosono Shinya , Yang Jianhui
Published: March 2022

The conversion of p-nitrophenol (4-NP) to p-aminophenol (4-AP) is of great significance for pharmaceutical and material manufacturing. In this work, Au-M@SiO2 (M = Rh, Pd, Ir, Pt) nanoparticles (NPs) with core-shell structures, which are expected to be excellent catalysts for the transformation of 4-NP to 4-AP, were synthesized by a facile one-pot one-step method. The structure and composition of the NPs were characterized through transmission electron microscopy (TEM), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Au-M@SiO2 (M = Rh, Pd, Ir, Pt) core-shell NPs showed excellent catalytic activity in the reduction of 4-NP, which is superior to most catalysts reported in the previous literature. The enhanced catalytic activity of Au-M@SiO2 core-shell NPs is presumably related to the bimetallic synergistic effect. This study provides a simple strategy to synthesize core-shell bimetallic NPs for catalytic applications.
Cognitive Functional Therapy (CFT) compared with a combined Core Training Exercise and Manual Therapy in patients with non-specific chronic low back pain: a study protocol for a randomized controlled trial
Authors: Castro Julia , Donato Bruno de Sousa , Arruda Bruno , Pellegrini Marina Jacobucci , de Souza Cíntia Pereira , Fernandez Jessica , Reis Felipe José Jandre , Correa Luis Claudio Lemos , Meziat-Filho Ney
Published: March 2022

Background: Chronic non-specific low back pain (CNSLBP) is a public health issue associated with a complex interaction of biopsychosocial factors. Cognitive Functional Therapy is a multidimensional approach for CNSLBP which targets negative cognitions and maladaptive functional behaviors (via body relaxation, control and extinction of protective and safety behaviors). Since the evidence about the efficacy of CFT is still limited, it is important to perform clinical trials with the aim of comparing CFT with other interventions commonly used in clinical practice of physiotherapy. The current study will investigate the efficacy of Cognitive Functional Therapy (CFT) compared to combined Core Training exercise and manual therapy (CORE-MT) on pain and disability in patients with CNSLBP. Methods: Two-group, randomized controlled trial with blinded assessors. We will recruit 148 patients with CNSLBP in a private clinic in the city of Campinas, Brazil. The experimental group will receive five one-hour individualized sessions of CFT within a period of two months. The control group will receive five one-hour individualized sessions of CORE-MT within a period of two months. Patients will be assessed pre-intervention, post-intervention and after six and twelve months. The primary outcomes will be pain intensity and disability two months after first intervention session; secondary outcomes will be pain intensity and disability at six and twelve months, as well as global perceived effect and patient satisfaction at two, six and twelve months after the first intervention session. Non-specific predictors, moderators and mediators of outcomes will also be analyzed. Discussion: The result of a high-quality randomized controlled clinical trial involving CFT will assist physiotherapists in the clinical decision-making process. The present study will have a sample size capable of detecting relevant clinical effects of treatment with a low risk of bias. Trial registration: The protocol has been written according to the SPIRIT statement to enhance transparency of content and completeness, has been approved by the Augusto Motta University Center Ethics Committee (research protocol number 2.219.742) and the findings of the trial will be reported following the CONSORT statement and the TIDieR checklist. Trial registration number: NCT03273114
Plasmon-induced flexibility and refractive index measurement in a sensor designed by a cavity, two rings, two teeth and two plasmonic waveguides.
Authors: HamidAbbasi
Published: March 2022

In this research, we design a plasmonic refractive index sensor and examine it numerically, using transparency, refractive index, sensitivity, FOM fit shape and Q quality factor, to optimize and improve performance quality. We will be. To design the structure of this sensor, we use two plasmonic waveguides, a cavity, two rings and two teeth. The resonant wavelengths and refractive index of the resonators are investigated and simulated by the finite difference time domain (FDTD) method, and we draw the obtained diagrams using MATLAB software. After completing the sensor design, due to the fact that the amplifiers are very sensitive to changes in the refractive index, so by changing the refractive index and changing the dimensions of the structure, we can weaken or strengthen the passage coefficient in the resonant modes. These plasmonic sensors with a simple frame and high optical resolution can be used to measure refractive index in the medical, chemical and food industries.