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1. FUSE (Fusion Synthesis Engine): A Next Generation Framework for Integrated Design of Fusion Pilot Plants

Author

Meneghini, O., Slendebroek, T., Lyons, B. C., McLaughlin, K., McClenaghan, J., Stagner, L., Harvey, J., Neiser, T. F., Ghiozzi, A., Dose, G., Guterl, J., Zalzali, A., Cote, T., Shi, N., Weisberg, D., Smith, S. P., Grierson, B. A., and Candy, J.

Subjects
Physics - Plasma Physics
Abstract

The Fusion Synthesis Engine (FUSE) is a state-of-the-art software suite designed to revolutionize fusion power plant design. FUSE integrates first-principle models, machine learning, and reduced models into a unified framework, enabling comprehensive simulations that go beyond traditional 0D systems studies. FUSE's modular structure supports a hierarchy of model fidelities, from steady-state to time-dependent simulations, allowing for both pre-conceptual design and operational scenario development. This framework accelerates the design process by enabling self-consistent solutions across physics, engineering, and control systems, minimizing the need for iterative expert evaluations. Leveraging modern software practices and parallel computing, FUSE also provides multi-objective optimization, balancing cost, efficiency, and operational constraints. Developed in Julia, FUSE is fully open-source under the Apache 2.0 license, promoting transparency and collaboration within the fusion research community.

Published
2024

2. Microenvironmental Enzyme-Responsive Methotrexate Modified Quercetin Micelles for the Treatment of Rheumatoid Arthritis

Author

Li X, Wang X, Qu X, Shi N, Li Q, Yan Z, Li Y, and Wang Y

Subjects
matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory, Medicine (General), R5-920
Abstract

Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of (89.62 ± 1.33) nm and a zeta potential of (− 4.9 ± 0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ± 6.98) μmol/L was significantly lower than that of free Que (141.10 ± 6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats.Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.Keywords: matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory

Published
2024

3. Pediatric Mycotic Pseudoaneurysm of the Ascending Aorta: A Case Report

Author

Song JG, Yang ZX, Shi N, and Zhu M

Subjects
aorta, mycotic, pseudoaneurysm, Infectious and parasitic diseases, RC109-216
Abstract

Jia-Guang Song,1,2,* Zi-Xin Yang,2,* Na Shi,3 Mei Zhu2 1Department of Ultrasound, Shandong Provincial Hospital, Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Ultrasound, Linyi Mental Health Center, Linyi, 276001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Zhu, Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 15653101616, Fax +86 53168778113, Email zhumei75@126.comAbstract: Mycotic pseudoaneurysm of the ascending aorta is extremely uncommon, particularly in children with no prior cardiac surgery or trauma. We report a rare case of a mycotic pseudoaneurysm of the ascending aorta in a 2-year-old girl with no history of cardiac surgery. Investigations revealed a methicillin-resistant Staphylococcus aureus infection and significant pericardial effusion in the child who presented with persistent fever and altered mental state. Cardiac ultrasound revealed a disruption in the aortic wall and a tumor-like structure. Contrast-enhanced computed tomography confirmed an ascending aortic pseudoaneurysm with thrombus. The child underwent successful surgical treatment without implants. This case emphasizes the diagnostic significance of imaging, particularly the advantages of ultrasound in pediatric settings, and the need for timely and accurate diagnosis using appropriate imaging modalities in children.Keywords: aorta, mycotic, pseudoaneurysm

Published
2023

4. Compression Degree of Trigeminal Nerve and Type of Conflicting Vessels Determine Short- and Long-Term Complete Pain Relief in Adult Patients with Primary Trigeminal Neuralgia After Microvascular Decompression: A Three-Year Retrospective Study of 200 Adult Patients with Primary Trigeminal Neuralgia

Author

Zhao ZF, Liu BB, Zhang JN, Shi N, Zhang P, Yang GZ, Cao YF, Tian LH, Qiu CC, and Gao Y

Subjects
compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia, Medicine (General), R5-920
Abstract

Zhe-Feng Zhao,1,* Bing-Bing Liu,1,* Jian-Nan Zhang,2,* Ni Shi,3,* Ping Zhang,1,* Gang-Zhi Yang,4 Yu-Fu Cao,4 Long-He Tian,4 Cheng-Cai Qiu,5 Yang Gao6,7 1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Neurosurgery, People’s Hospital of Hegang City, Hegang, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, Traditional Chinese Medicine Hospital of Jixi City, Jixi, Heilongjiang, People’s Republic of China; 6Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhe-Feng Zhao, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email know810512@163.com Yang Gao, Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email gaoyang0312@126.comObjective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice.Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient’s subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat.Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively.Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.Keywords: compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia

Published
2023

5. Characteristics, Outcomes, and Clinical Indicators of Bloodstream Infections in Neutropenic Patients with Hematological Malignancies: A 7-Year Retrospective Study

Author

Wang S, Song Y, Shi N, Yin D, Kang J, Cai W, and Duan J

Subjects
bloodstream infection, neutropenia, hematological malignancy, pathogens distribution, antibiotic susceptibility, risk factors., Infectious and parasitic diseases, RC109-216
Abstract

Shuyun Wang,1 Yan Song,1 Nan Shi,1,2 Donghong Yin,1 Jianbang Kang,1 Wanni Cai,2 Jinju Duan1 1Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Jinju Duan, Department of Pharmacy, Second Hospital of Shanxi Medical University, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Tel +86 13834653172, Email duanjinju@163.comPurpose: The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors.Patients and Methods: We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index’s reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve.Results: A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for > 20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections.Conclusion: We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.Keywords: bloodstream infection, neutropenia, hematological malignancy, pathogens distribution, antibiotic susceptibility, risk factors

Published
2023

6. Development of CFETR scenarios with self-consistent core-pedestal coupled simulations

Author

Deng, Zhao, Lao, L. L., Chan, V. S., Prater, R., Li, J., Chen, Jiale, Jian, X., Shi, N., Meneghini, O., Staebler, G. M., Liu, Y. Q., Turnbull, A. D., Candy, J., Smith, S. P., Snyder, P. B., and team, CFETR physics

Subjects
Physics - Plasma Physics
Abstract

This paper develops two non-inductive steady state scenarios for larger size configuration of China Fusion Engineering Test Reactor (CFETR) with integrated modeling simulations. A self-consistent core-pedestal coupled workflow for CFETR is developed under integrated modeling framework OMFIT, which allows more accurate evaluation of CFETR performance. The workflow integrates equilibrium code EFIT, transport codes ONETWO and TGYRO, and pedestal code EPED. A fully non-inductive baseline phase I scenario is developed with the workflow, which satisfies the minimum goal of Fusion Nuclear Science Facility. Compared with previous work, which proves the larger size and higher toroidal field CFETR configuration than has the advantages of reducing heating and current drive requirements, lowering divertor and wall power loads, allowing higher bootstrap current fraction and better confinement. A fully non-inductive high-performance phase II scenario is developed, which explores the alpha-particle dominated self-heating regime. Phase II scenario achieves the target of fusion power Pfus>1GW and fusion gain Qfus>20, and it largely reduces auxiliary heating and current drive power. Moreover, the large neutron production of phase II increases the energy generation power and tritium breeding rate.

Published
2019

7. Bacteriological Profile and Antimicrobial Susceptibility Patterns of Gram-Negative Bloodstream Infection and Risk Factors Associated with Mortality and Drug Resistance: A Retrospective Study from Shanxi, China

Author

Shi N, Kang J, Wang S, Song Y, Yin D, Li X, Guo Q, Duan J, and Zhang S

Subjects
gram-negative bloodstream infection, epidemiology, risk prediction model, mdr, esbl, carbapenem resistance, Infectious and parasitic diseases, RC109-216
Abstract

Nan Shi,1,2,&ast; Jianbang Kang,2,&ast; Shuyun Wang,2 Yan Song,2 Donghong Yin,2 Xiaoxia Li,2 Qian Guo,2 Jinju Duan,2 Shuqiu Zhang1 1Department of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinju Duan; Shuqiu Zhang, Email duanjinju@163.com; shuqiu.zhang@126.com; shuqiu.zhang@sxmu.edu.cnObjective: The aim of this study was to analyze the epidemiological of gram-negative bloodstream infection (GNBSI) and establish a risk prediction model for mortality and acquiring multidrug resistant (MDR), the extended spectrum beta-lactamases (ESBLs) producing and carbapenem-resistant (CR) GNBSI.Methods: This retrospective study covered five years from January 2015 to December 2019. Data were obtained from Hospital Information System (HIS) and microbiology department records. The risk factors for mortality and acquiring MDR, ESBLs-producing and CR GNBSI were analyzed by univariable and multivariable analysis.Results: A total of 1018 GNBSI cases were collected. A majority of GNBSI patients were in hematology ward (23.77%). There were 38.61% patients who were assigned in the 41– 60 age group. Escherichia coli was the most common gram-negative organism (49.90%). Among isolates of GNBSI, 40.47% were found to be MDR strains, 34.09% were found to be ESBLs-producing strains and 7.06% were found to be CR strains. Escherichia coli was the most common MDR (71.36%) and ESBLs-producing strain (77.81%). Acinetobacter baumannii was the most common CR isolate (46.15%). Multivariate analysis indicated that diabetes mellitus, solid organ tumor, non-fermentative bacteria, MDR strain, central venous cannula, urinary catheter, therapy with carbapenems or tigecycline prior 30 days of infection were independent mortality risk factors for GNBSIs. Over all, therapy with tigecycline prior 30 days of infection was the mutual predictor for mortality of GNBSI, acquiring MDR, ESBLs-producing and CR GNBSI (OR, 8.221, OR, 3.963, OR, 3.588, OR, 9.222, respectively, all p < 0.001).Conclusion: Collectively, our study implies that patients who were diagnosed as GNBSI had a younger age. Therapy with tigecycline was the mutual and paramount predictor for mortality of GNBSI, acquiring MDR, ESBLs-producing and CR GNBSI. Our investigation had provided a theoretical basis for the use of antibiotics and prevention and control of hospital infection in our region.Keywords: gram-negative bloodstream infection, epidemiology, risk prediction model, MDR, ESBL, carbapenem resistance

Published
2022

11. Mutations in gyrB play an important role in ciprofloxacin-resistant Pseudomonas aeruginosa

Author

Feng X, Zhang Z, Li X, Song Y, Kang J, Yin D, Gao Y, Shi N, and Duan J

Subjects
Pseudomonas aeruginosa, fluoroquinolones, molecular resistance mechanisms, in vitro, Infectious and parasitic diseases, RC109-216
Abstract

Xinyuan Feng,1,* Zhiqi Zhang,2,* Xiaoxia Li,3 Yan Song,3 Jianbang Kang,3 Donghong Yin,3 Yating Gao,3 Nan Shi,1 Jinju Duan3 1Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the main molecular resistance mechanisms to fluoroquinolones (FQs) in Pseudomonas aeruginosa and also to investigate the effect of time and concentration on mutations in resistance genes.Materials and methods: The clinical isolates of P. aeruginosa which are sensitive to ciprofloxacin (CIP) or levofloxacin (LEV) were collected. The isolates were incubated with different concentrations of CIP or LEV for 5 days and the minimal inhibitory concentrations (MICs) of CIP, LEV and ofloxacin (OFX) were measured. The MIC of FQs to P. aeruginosa was measured by the agar dilution method. FQ resistance determining regions of gyrA, gyrB, parC and parE were amplified by PCR, and mutations in four genes were explored using sequence analysis with the Snapgene software. The relative expression levels of two efflux pumps genes (mexA and mexE) were measured by quantitative reverse transcription PCR.Results: A total of eleven isolates were collected from the Second Hospital of Shanxi Medical University. Amino acid alterations in gyrA and gyrB were mainly detected in resistant mutants, and the percentage of strains with amino acid alterations in gyrB was significantly higher than that in gyrA (P0.05). No amino acid alterations were detected in genes of parC and parE. In both gyrA and gyrB, the number of amino acid alterations increased with incubation time prolonged and increased with increasing incubation concentration.Conclusion: CIP was more competent than LEV in making P. aeruginosa resistant to in vitro selection. Mutations occurring in gyrB played an important role in FQ resistance of P. aeruginosa in vitro selection. Keywords: Pseudomonas aeruginosa, fluoroquinolones, molecular resistance mechanisms, in vitro

Published
2019

17. Validation of D-T fusion power prediction capability against 2021 JET D-T experiments

Author

Kim, H, Auriemma, F, Ferreira, J, Gabriellini, S, Ho, A, Huynh, P, Kirov, K, Lorenzini, R, Marin, M, Poradzinski, M, Shi, N, Staebler, G, Stancar, Z, Stankunas, G, Zotta, V, Belli, E, Casson, F, Challis, C, Citrin, J, van Eester, D, Fransson, E, Gallart, D, Garcia, J, Garzotti, L, Gatto, R, Hobirk, J, Kappatou, A, Lerche, E, Ludvig-Osipov, A, Maggi, C, Maslov, M, Nocente, M, Sharma, R, Di Siena, A, Strand, P, Tholerus, E, Yadykin, D, Kim, HT, Ho, AR, Zotta, VK, Casson, FJ, Kim, H, Auriemma, F, Ferreira, J, Gabriellini, S, Ho, A, Huynh, P, Kirov, K, Lorenzini, R, Marin, M, Poradzinski, M, Shi, N, Staebler, G, Stancar, Z, Stankunas, G, Zotta, V, Belli, E, Casson, F, Challis, C, Citrin, J, van Eester, D, Fransson, E, Gallart, D, Garcia, J, Garzotti, L, Gatto, R, Hobirk, J, Kappatou, A, Lerche, E, Ludvig-Osipov, A, Maggi, C, Maslov, M, Nocente, M, Sharma, R, Di Siena, A, Strand, P, Tholerus, E, Yadykin, D, Kim, HT, Ho, AR, Zotta, VK, and Casson, FJ

Abstract

JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D-T), provide a unique opportunity to validate existing D-T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D-T experimental campaign has achieved D-T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D-T experimental campaign, extensive D-T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D-T predictive modelling in the future, it is important to use the input data measured from 2021 JET D-T discharges in the present core predictive modelling, and to specify the accuracy of the D-T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D-T discharges. Detailed simulation settings and the heating and transport models used are described. The D-T fusion power calculated with the interpretive TRANSP runs for 38 D-T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 % . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than 20 % in total. The good statistical agreement confirms that we have the capability to accurately calculate the D-T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D-T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinet

Published
2023

18. Smartphone-delivered multicomponent lifestyle medicine intervention for improving mental health in a nonclinical population: a randomized controlled trial.

Author

Wong, VW-H, Tong, JT-Y, Shi, N-K, Ng, CH, Sarris, J, Ho, FY-Y, Wong, VW-H, Tong, JT-Y, Shi, N-K, Ng, CH, Sarris, J, and Ho, FY-Y

Abstract

OBJECTIVE: To prevent the exacerbation of mental health burdens, a growing body of research has recommended a balanced approach that emphasizes both the delivery of mental health treatments to individuals with common mental disorders (CMDs) and the strengthening of protective factors for CMDs among nonclinical populations. This randomized controlled trial (RCT) evaluated the efficacy of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, for improving mental health among a nonclinical population of Chinese adults. METHODS: A total of 106 participants with Patient Health Questionnaire-9 total score < 10 and Generalized Anxiety Disorder 7-Item Scale <8 were randomly assigned to either the Lifestyle Hub intervention group (LH, n = 53) or the waitlist control group (WL, n = 53). Lifestyle Hub is an 8-week smartphone-delivered multicomponent LM intervention developed based on the transtheoretical model. The intervention components included lifestyle psychoeducation, physical activity, diet and nutrition, stress management, sleep management, and motivation and goal-setting techniques. Assessments were conducted at baseline, immediate post-intervention, and 1-month follow-up (LH only). RESULTS: The linear mixed effect model based on the intention-to-treat principle indicated that Lifestyle Hub significantly improved overall mental health, depressive symptoms, anxiety symptoms, stress, insomnia severity, overall health-promoting behaviors, dietary quality, and stress management compared to the WL group at immediate post-intervention (d = 0.13-0.56). No significant between-group differences were observed in terms of functional impairment, health-related quality of life, health responsibility, physical activity level, spiritual growth, and interpersonal relations. The intervention gains in the LH group were maintained at 1-month follow-up. The LH participants indicated that Lifestyle Hub was an acceptable intervention for improving menta

Published
2023

25. A Self-Organizing Link Layer Protocol for UWB Ad Hoc Networks

Author

Shi, N., Niemegeers, I. G. M. M., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Niemegeers, Ignas, editor, and de Groot, Sonia Heemstra, editor

Published
2004
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30. Comparison of Real-World Treatment Patterns Among Psoriasis Patients Treated with Ixekizumab or Adalimumab

Author

Blauvelt A, Shi N, Burge R, Malatestinic WN, Lin CY, Lew CR, Zimmerman NM, Goldblum OM, Zhu B, and Murage MJ

Subjects
lcsh:R5-920, ixekizumab, adalimumab, psoriasis, persistence, lcsh:Medicine (General), treatment switching, discontinuation
Abstract

Andrew Blauvelt,1 Nianwen Shi,2 Russel Burge,3,4 William N Malatestinic,3 Chen-Yen Lin,3 Carolyn R Lew,2 Nicole M Zimmerman,2 Orin M Goldblum,3 Baojin Zhu,3 Mwangi J Murage3 1Oregon Medical Research Center, Portland, OR, USA; 2IBM Watson Health, Cambridge, MA, USA; 3Eli Lilly and Company, Indianapolis, IN, USA; 4University of Cincinnati, Cincinnati, OH, USACorrespondence: Mwangi J MurageGlobal Patient Outcomes and Real World Evidence (GPORWE), Eli Lilly and Company, LCT – South Building 171-2, Drop Code 5221, 1555 Harding St, Indianapolis, IN 46221, USATel +1-317-460-3619Email murage_mwangi_james@lilly.comBackground: There is lack of real-world treatment pattern comparison data between ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis.Objective: To compare real-world treatment patterns among psoriasis patients initiating ixekizumab or adalimumab in the United States.Methods: Psoriasis patients with ≥ 1 claim for ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan® databases. Patients were required to be continuously enrolled for ≥ 12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence.Results: A total of 646 ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69– 0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62– 0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57– 0.91). Ixekizumab users had higher odds of medication possession ratio ≥ 80% (odds ratio [OR]=1.36, 95% CI: 1.10– 1.69) but similar odds by proportion of days covered ≥ 80% (OR=1.22, 95% CI: 0.98– 1.53).Conclusion: Psoriasis patients treated with ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥ 80%, it did not by PDC ≥ 80%; hence, further analysis using fixed-length follow-up is required.Keywords: ixekizumab, adalimumab, psoriasis, treatment switching, discontinuation, persistence

Published
2020

34. Lifestyle medicine for anxiety symptoms: A meta-analysis of randomized controlled trials.

Author

Wong, VW-H, Ho, FY-Y, Shi, N-K, Sarris, J, Ng, CH, Tam, OK-Y, Wong, VW-H, Ho, FY-Y, Shi, N-K, Sarris, J, Ng, CH, and Tam, OK-Y

Abstract

BACKGROUND: Lifestyle medicine (LM) is gaining increasing attention as a treatment option for anxiety, but the current state of evidence has not yet been systematically examined. METHODS: Six electronic databases were systematically searched from inception to February 2022. Randomized controlled trials (RCTs) comparing the effects of multicomponent LM interventions on anxiety symptoms with either care-as-usual, waitlist, no intervention, or attention control group on anxiety symptoms were identified. RESULTS: A total of 53 RCTs with 18,894 participants were included for qualitative synthesis, in which 45 RCTs with data available were included for meta-analysis. Multicomponent LM intervention was significantly more effective than the control groups in reducing anxiety symptoms at immediate posttreatment (d = 0.19, p < .001) and at short-term follow-up (d = 0.29, p < .001). However, no significant difference at medium-term was found (p = .14), whereas more studies are needed to study the long-term effects. The subgroup analyses suggested that baseline anxiety symptoms was a significant moderator, suggesting that those with moderate level of baseline anxiety symptoms appeared to have greater improvements (d = 0.66, p < .05). LIMITATIONS: Minimal anxiety symptoms at baseline contributed to the floor effect and influenced the degree of improvement. The included RCTs had a high risk of bias in general with potential publication bias detected. CONCLUSION: The findings of this meta-analysis provided support for the positive effects of multicomponent LM interventions for anxiety symptoms. Future research is needed to determine the long-term effects of multicimponent LM and the optimal baseline anxiety severity.

Published
2022

37. Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway

Author

Shi N, Yu H, and Chen T

Subjects
Esophageal squamous cell carcinoma, PI3K/AKT/mTOR, MK2206, BEZ235, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Ni Shi,* Hao Yu,* Tong Chen Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA*These authors contributed equally to this workCorrespondence: Tong ChenDivision of Medical Oncology, Department of Internal Medicine, The Ohio State University, 410 West 12 th Ave., Room 302C, Columbus, Ohio 43210, USATel +1 614 685 9119Fax +1 614 293 3349Email tong.chen@osumc.eduBackground: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is implicated in several cancers. AKT allosteric inhibitor MK2206 and dual PI3K and mTOR inhibitor BEZ235 are promising drug candidates with potential anti-tumor effects.&#x00A0Purpose: In this study, we aimed to detect the activation of PI3K/AKT/mTOR pathway and assess the efficacy of MK2206 and BEZ235 in inhibiting esophageal cancer growth.Materials and methods: We used three different systems including carcinogen-induced animal model, human esophageal squamous cell carcinoma (SCC) cell lines, and xenograft mouse model.&#x00A0Results: Our data indicated that components of the PI3K/AKT/mTOR pathway were overexpressed and activated in esophageal SCC. MK2206 and BEZ235 inhibited cell proliferation, enhanced apoptosis, and induced cell-cycle arrest through downstream effectors SKP2, MCL-1, and cyclin D1 in esophageal SCC cells. MK2206 and BEZ235 also inhibited tumor growth in xenograft mice through the inhibition of AKT phosphorylation. MK2206/BEZ235 combination showed greater anti-tumor effect than MK2206 or BEZ235 alone. The enhanced efficacy of the combination was associated with the inhibition of phosphorylation ATK on both Thr308 and Ser473.&#x00A0Conclusion: The combination of MK2206 and BEZ235 exhibits potent antitumor effects and may have important clinical applications for esophageal SCC treatment.Keywords: PI3K/AKT/mTOR, MK2206, BEZ235, Esophageal squamous cell carcinoma

Published
2019

38. Nicotine promotes cervical metastasis of oral cancer by regulating peroxiredoxin 1 and epithelial–mesenchymal transition in mice

Author

Wang M, Niu W, Qi M, Chen H, Zhang M, Wang C, Ge L, Yang J, Miao C, Shi N, Chen T, and Tang X

Subjects
oral squamous cell carcinoma, stomatognathic diseases, peroxiredoxin 1, mouse model, epithelial-mesenchymal transition, metastasis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Min Wang,1 Wenwen Niu,2 Moci Qi,1 Hui Chen,1 Min Zhang,1 Chunxiao Wang,1 Lihua Ge,1 Jing Yang,1 Congcong Miao,1 Ni Shi,3 Tong Chen,3 Xiaofei Tang1 1Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing 100050, People’s Republic of China; 2Beijing Shibalidian Community Hospital, Beijing, People’s Republic of China; 3Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA Background: Tobacco is a major risk factor for oral squamous cell carcinoma (OSCC). However, the role of nicotine in OSCC is not completely understood. Materials and methods: To analyze the mechanisms of nicotine-induced cervical metastasis, we investigated whether nicotine induced invasion, migration, and epithelial–mesenchymal transition (EMT) via regulating peroxiredoxin 1 (Prx1) in CAL 27 cells. In addition, we established a mouse model to confirm the roles of nicotine in regulating Ets1/Prx1/EMT signaling in OSCC metastasis. Results: We showed that nicotine induced CAL 27 cell invasion, migration, EMT, and Prx1 and Ets1 expression. Prx1 knockdown inhibited cell invasion, migration, and EMT. Ets1 silencing downregulated Prx1 expression and EMT. Prx1 and Ets1 were shown to interact in CAL 27 cells treated with nicotine, and nicotine could significantly upregulate the binding of the transcription factor Ets1 to the Prx1 gene promoter region. Additionally, an invivo study showed that nicotine induced tumor metastasis and EMT. Prx1 knockdown inhibited cervical metastasis rates and EMT progression. No significant differences in metastasis rates and EMT-related marker expression levels were observed between vehicle- and nicotine-treated mice. Conclusion: The results indicate that nicotine promotes cervical lymph node metastasis through regulating Ets1/Prx1/EMT signaling during OSCC pathogenesis; consequently, Prx1 may represent a potential target for the prevention and treatment of OSCC. Keywords: oral squamous cell carcinoma, peroxiredoxin 1, metastasis, epithelial–mesenchymal transition, mouse model

Published
2019

39. Mortality trends of bladder cancer in China from 1991 to 2015: an age-period-cohort analysis

Author

Yang Y, Cheng Z, Jia X, Shi N, Xia Z, Zhang W, and Shi X

Subjects
cohort effect, age effect, bladder cancer, period effect, intrinsic estimator, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Yongli Yang,1 Zhiwei Cheng,2 Xiaocan Jia,1 Nian Shi,3 Zhenhua Xia,1 Weiping Zhang,1 Xuezhong Shi1 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China; 2Department of Case Management, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; 3Department of Physical Diagnosis, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Purpose: The effects of age, period, and cohort on mortality rates of bladder cancer in China remained vague. This study aimed to analyze the secular trends of bladder cancer mortality in China and estimate the independent effects of age, period, and cohort. Methods: Data for bladder cancer mortality from 1991 to 2015 was obtained from the WHO Mortality Database and China Health Statistical Yearbook. The age-period-cohort model was used to estimate the effect of age, period, and cohort. The intrinsic estimator method was used to solve the nonidentification problem of collinearity among age, period, and cohort. Results: The age-standardized mortality rates of total residents (2.33–1.87/100,000), male (3.45–2.89/100,000), and female (1.24–0.82/100,000) showed decreasing trends, which was more obvious in males than in females. Age effects increased consistently with age in all age groups (coefficients: –2.02 to 1.91 in the total population, –2.06 to 2.02 in males and –2.04 to 1.81 in females). Cohort effects decreased overall (coefficients: 0.96 to –1.62 in the total population, 1.11 to –1.66 in males and 0.78 to –1.46 in females). Period effects were not found in China. Conclusion: Although a decreasing mortality was observed, the bladder cancer burden in China will likely increase in the next few years due to population aging, environmental pollution, and food safety. The findings suggested that preventive measures should be taken corresponding to the changes in age-and cohort-related factors in the population. Keywords: bladder cancer, age effect, period effect, cohort effect, intrinsic estimator

Published
2019

42. Assessment of network module identification across complex diseases

Author

Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., Cowen L. J., Choobdar, S, Ahsen, M, Crawford, J, Tomasoni, M, Fang, T, Lamparter, D, Lin, J, Hescott, B, Hu, X, Mercer, J, Natoli, T, Narayan, R, Aicheler, F, Amoroso, N, Arenas, A, Azhagesan, K, Baker, A, Banf, M, Batzoglou, S, Baudot, A, Bellotti, R, Bergmann, S, Boroevich, K, Brun, C, Cai, S, Caldera, M, Calderone, A, Cesareni, G, Chen, W, Chichester, C, Cowen, L, Cui, H, Dao, P, De Domenico, M, Dhroso, A, Didier, G, Divine, M, del Sol, A, Feng, X, Flores-Canales, J, Fortunato, S, Gitter, A, Gorska, A, Guan, Y, Guenoche, A, Gomez, S, Hamza, H, Hartmann, A, He, S, Heijs, A, Heinrich, J, Hu, Y, Huang, X, Hughitt, V, Jeon, M, Jeub, L, Johnson, N, Joo, K, Joung, I, Jung, S, Kalko, S, Kamola, P, Kang, J, Kaveelerdpotjana, B, Kim, M, Kim, Y, Kohlbacher, O, Korkin, D, Krzysztof, K, Kunji, K, Kutalik, Z, Lage, K, Lang-Brown, S, Le, T, Lee, J, Lee, S, Li, D, Li, J, Liu, L, Loizou, A, Luo, Z, Lysenko, A, Ma, T, Mall, R, Marbach, D, Mattia, T, Medvedovic, M, Menche, J, Micarelli, E, Monaco, A, Muller, F, Narykov, O, Norman, T, Park, S, Perfetto, L, Perrin, D, Pirro, S, Przytycka, T, Qian, X, Raman, K, Ramazzotti, D, Ramsahai, E, Ravindran, B, Rennert, P, Saez-Rodriguez, J, Scharfe, C, Sharan, R, Shi, N, Shin, W, Shu, H, Sinha, H, Slonim, D, Spinelli, L, Srinivasan, S, Subramanian, A, Suver, C, Szklarczyk, D, Tangaro, S, Thiagarajan, S, Tichit, L, Tiede, T, Tripathi, B, Tsherniak, A, Tsunoda, T, Turei, D, Ullah, E, Vahedi, G, Valdeolivas, A, Vivek, J, von Mering, C, Waagmeester, A, Wang, B, Wang, Y, Weir, B, White, S, Winkler, S, Xu, K, Xu, T, Yan, C, Yang, L, Yu, K, Yu, X, Zaffaroni, G, Zaslavskiy, M, Zeng, T, Zhang, J, Zhang, L, Zhang, W, Zhang, X, Zhou, X, Zhou, J, Zhu, H, Zhu, J, Zuccon, G, Stolovitzky, G, Choobdar S., Ahsen M. E., Crawford J., Tomasoni M., Fang T., Lamparter D., Lin J., Hescott B., Hu X., Mercer J., Natoli T., Narayan R., Aicheler F., Amoroso N., Arenas A., Azhagesan K., Baker A., Banf M., Batzoglou S., Baudot A., Bellotti R., Bergmann S., Boroevich K. A., Brun C., Cai S., Caldera M., Calderone A., Cesareni G., Chen W., Chichester C., Cowen L., Cui H., Dao P., De Domenico M., Dhroso A., Didier G., Divine M., del Sol A., Feng X., Flores-Canales J. C., Fortunato S., Gitter A., Gorska A., Guan Y., Guenoche A., Gomez S., Hamza H., Hartmann A., He S., Heijs A., Heinrich J., Hu Y., Huang X., Hughitt V. K., Jeon M., Jeub L., Johnson N. T., Joo K., Joung I. S., Jung S., Kalko S. G., Kamola P. J., Kang J., Kaveelerdpotjana B., Kim M., Kim Y. -A., Kohlbacher O., Korkin D., Krzysztof K., Kunji K., Kutalik Z., Lage K., Lang-Brown S., Le T. D., Lee J., Lee S., Li D., Li J., Liu L., Loizou A., Luo Z., Lysenko A., Ma T., Mall R., Marbach D., Mattia T., Medvedovic M., Menche J., Micarelli E., Monaco A., Muller F., Narykov O., Norman T., Park S., Perfetto L., Perrin D., Pirro S., Przytycka T. M., Qian X., Raman K., Ramazzotti D., Ramsahai E., Ravindran B., Rennert P., Saez-Rodriguez J., Scharfe C., Sharan R., Shi N., Shin W., Shu H., Sinha H., Slonim D. K., Spinelli L., Srinivasan S., Subramanian A., Suver C., Szklarczyk D., Tangaro S., Thiagarajan S., Tichit L., Tiede T., Tripathi B., Tsherniak A., Tsunoda T., Turei D., Ullah E., Vahedi G., Valdeolivas A., Vivek J., von Mering C., Waagmeester A., Wang B., Wang Y., Weir B. A., White S., Winkler S., Xu K., Xu T., Yan C., Yang L., Yu K., Yu X., Zaffaroni G., Zaslavskiy M., Zeng T., Zhang J. D., Zhang L., Zhang W., Zhang X., Zhang J., Zhou X., Zhou J., Zhu H., Zhu J., Zuccon G., Stolovitzky G., and Cowen L. J.

Abstract

Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the ‘Disease Module Identification DREAM Challenge’, an open competition to comprehensively assess module identification methods across diverse protein–protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology.

Published
2019

47. Notch signaling promotes serrated neoplasia pathway in colorectal cancer through epigenetic modification of EPHB2 and EPHB4

Author

Lian H, Jia X, Shi N, Xie S, Wang J, Wang W, Ma F, Liu H, Wang A, Cheng X, and Liu C

Subjects
Eph gene, colorectal cancer, histone methylation, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Notch signaling
Abstract

Haifeng Lian,1,* Xingfang Jia,1,* Ning Shi,1 Shuyang Xie,2 Jian Wang,1 Wei Wang,1 Fengzhen Ma,1 Haiyan Liu,1 Aili Wang,1 Xiankui Cheng,3 Chengxia Liu1 1Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China; 2Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, China; 3Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China *These authors contributed equally to this work Background: Dysregulation of erythropoietin-producing hepatoma (Eph) proteins in human cancers is extensively documented but not clear in colorectal cancer (CRC). In this study, we aimed to investigate the role of Notch signaling pathway and epigenetic modification of EPHB2 and EPHB4 expression in serrated neoplasia development. Methods: The expression of EPHB2 and EPHB4 in CRC clinical specimens and cell lines were determined by immunohistochemistry, Western blot, and real-time PCR. Cell proliferation and invasion were evaluated by MTT and chamber kits, luciferase assay and co-immunoprecipitation were used to detect the transcriptional regulation and protein–protein interactions, respectively. The immunofluorescence assay was employed to confirm the subcellular location of Notch intracellular domain (NICD), and chromatin immunoprecipitation assay was implied to detect the modification types of H3K4me3 and H3K27me3. Mice xenograft model was used to detect the in vivo effects of EPHB2 and EPHB4 genes on cell growth. Results: In CRC clinical specimens and cell lines, we found that EPHB2 was significantly decreased, while EPHB4 was elevated in the CRC tissues, and these aberrant expression manners correlated with worse overall survival rates in the clinic. When the EPHB2 and EPHB4 expressions were manipulated by overexpression or knockdown in the SW620 cells, the cell proliferation and invasion were obviously suppressed, whereas EPHB2 knockdown or EPHB4 overexpression showed the opposite phenotypes. We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. Conclusion: Taken together, we provide a new mechanistic option in understanding the role of Notch signaling and the roles of EPHB2 and EPHB4 in CRC. Keywords: Notch signaling, Eph gene, histone methylation, colorectal cancer

Published
2018

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