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947 results on '"Xia Tian"'

1. Exosomal miR-192-5p secreted by bone marrow mesenchymal stem cells inhibits hepatic stellate cell activation and targets PPP2R3A

Author: Jie Tan, Mingtao Chen, Meng Liu, Aifang Chen, Min Huang, Xiaoli Chen, Xia Tian, and Wei Chen
Subjects: Medical Laboratory Technology, Histology, Anatomy
Published: 2023
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2. Effects of Intradermal Botulinum Toxin Injections on Herpes Zoster Related Neuralgia

Author: Peng,Fen and Xia,Tian-Bao
Subjects: Pharmacology, Infectious Diseases, Infection and Drug Resistance, Pharmacology (medical)
Abstract: Fen Peng,1 Tian-Bao Xia2 1Department of Dermatology, Peking University Third Hospital, Beijing, Peopleâs Republic of China; 2Department of Dermatology, Peopleâs Liberation Army Strategic Support Force Characteristic Medical Center, Beijing, Peopleâs Republic of ChinaCorrespondence: Tian-Bao Xia, Department of Dermatology, Peopleâs Liberation Army Strategic Support Force Characteristic Medical Center, No. 9th Anxiang Beili Road, Chaoyang District, Beijing, 100101, Peopleâs Republic of China, Email xtb78@163.comBackground: Postherpetic neuralgia (PHN), which represents the most common chronic complication of herpes zoster, is characterized by intense pain and is difficult to treat. In fact, no treatments are currently available that can effectively reduce the pain associated with PHN. Recent evidence has been presented indicating that Botulinum toxin (BoNT-A) can serve as an effective and safe treatment for peripheral neuropathic pain.Objective: The effects of intradermal BoNT-A injections on herpes zoster related neuralgia were investigated in this study.Methods: Patients diagnosed with herpes zoster related acute neuralgia (N=13 â acute group) and those diagnosed with postherpetic neuralgia (N=17 - PHN group) were enrolled in this study. The two groups were treated with intradermal injections of BoNT-A at the site of their affected pain areas and were then assessed at 1 day, 1 week, 2 weeks, 1 month, 2 months and 3 months after their BoNT-A treatments.Results: When compared with pre-treatment values, Visual Analogue Scores (VAS) in all patients were all significantly decreased at all times tested following BoNT-A injection. Before treatment, PHN patients had significantly higher VAS than those in the acute group. However, after 1 day of treatment, there was no difference in VAS between the two groups. None of the patients in the acute phase treated with BoNT-A developed PHN.Conclusion: BoNT-A injections significantly reduced herpetic-related pain and proved to be a more effective treatment for the PHN versus acute pain group. Moreover, an early application of BoNT-A can alleviate the probability of developing PHN.Keywords: herpes zoster, postherpetic neuralgia, botulinum toxin
Published: 2023
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3. Poor response to sintilimab plus chemotherapy in a pulmonary epithelioid hemangioendothelioma patient: a case report

Author: Hao Zeng, Xiaojun Tang, Xia Tian, Yujie Liu, and Panwen Tian
Subjects: Oncology, Immunology, Immunology and Allergy
Abstract: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor with no established treatment protocol. The authors report the case of a young woman diagnosed with PEH. DNA and RNA analysis by next-generation sequencing was performed on the tumor tissue. A novel germline PALB2 mutation and classical WWTR1-CAMTA1 fusion were identified. She experienced a poor response to sintilimab (a PD-1 inhibitor) plus platinum-based chemotherapy as the first-line treatment. PEH patients harboring a germline PALB2 mutation and WWTR1-CAMTA1 gene fusion may respond poorly to treatment with PD-1 inhibitors plus chemotherapy.
Published: 2023
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4. Insights into enhanced removal of Cd2+ from aqueous solutions by attapulgite supported sulfide-modified nanoscale zero-valent iron

Author: Jun Ren, Gui Ma, Weifan Zhao, Ling Tao, Yue Zhou, Caiyun Liao, Xia Tian, Huan Wang, Kai Meng, Yongjie He, and Liang Dai
Subjects: Environmental Engineering, Water Science and Technology
Abstract: The sulfidation of nanoscale zerovalent iron (nZVI) has received increasing attention for reducing the oxidizability of nZVI and improving its reactivity toward heavy metal ions. Here, a sulfide (S)-modified attapulgite (ATP)-supported nanoscale nZVI composite (S-nZVI@ATP) was rapidly synthesized under acidic conditions and used to alleviate Cd2+ toxicity from an aqueous solution. The degree of oxidation of S-nZVI@ATP was less than that of nZVI@ATP, indicating that the sulfide modification significantly reduced the oxidation of nZVI. The optimal loading ratio was at an S-to-Fe molar ratio of 0.75, and the adsorption performance of S-nZVI@ATP for Cd2+ was significantly improved compared with that of nZVI@ATP. The removal of Cd2+ by S-nZVI@ATP was 100% when the adsorbent addition was 1 g/L, the solution was 30 mL, and the adsorption was performed at 25 °C for 24 h with an initial Cd2+ concentration of 100 mg/L. Kinetics studies showed that the adsorption process of Cd followed the pseudo-second-order model, indicating that chemisorption was the dominant adsorption mechanism. The adsorption of Cd2+ by S-nZVI @ATP is dominated by the complexation between the iron oxide or iron hydroxide shell of S-nZVI and Cd2+ and the formation of Cd(OH)2 and CdS precipitates.
Published: 2022
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5. Cathode Interface Layer Based on Organosilica Nanodots for Efficient and Stable Inverted Organic Solar Cells

Author: Yuting Li, Mengqi Cui, Na Li, Xia Tian, Xiujuan Hao, Yangyang Zhang, Yuying Wang, Rong Wang, Qikun Rong, Guofu Zhou, and Li Nian
Subjects: Materials Chemistry, Electrochemistry, Energy Engineering and Power Technology, Chemical Engineering (miscellaneous), Electrical and Electronic Engineering
Published: 2022
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6. BnaMPK3s promote organ size by interacting with BnaARF2s in Brassica napus

Author: Xia Tian, Xiwen Yu, Zhijie Wang, Liang Guo, Jinxing Tu, Jinxiong Shen, Bin Yi, Tingdong Fu, Jing Wen, Chaozhi Ma, and Cheng Dai
Subjects: Plant Science, Agronomy and Crop Science, Biotechnology
Published: 2023
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7. Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3β and Nrf2/NQO1 pathways

Author: Sun, Xiao-Lei, Xia, Tian-Shuang, Jiang, Yi-Ping, Wang, Na-Ni, Xu, Ling-Chuan, Han, Ting, and Xin, Hai-Liang
Subjects: Molecular Medicine
Abstract: Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3β and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.
Published: 2022
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8. Screening of Proliferation-Related Genes and Pathological Changes in Thiram-Induced Tibial Dyschondroplasia

Author: Ali Raza Jahejo, Chen-Liang Zhang, Fazul Nabi, Nazeer Hussain Kalhoro, Qurban Ali Shah, Zohaib Ahmed Bhutto, Jin-Feng Zhao, Jin Yu, Guan-Bao Ning, Ding Zhang, Shu-Ming Chen, and Wen-Xia Tian
Subjects: Article Subject, Tibia, General Immunology and Microbiology, Proliferating Cell Nuclear Antigen, Animals, Growth Plate, General Medicine, Thiram, Osteochondrodysplasias, Chickens, Poultry Diseases, General Biochemistry, Genetics and Molecular Biology, Cell Proliferation
Abstract: Aim and Background. Tibial dyschondroplasia (TD) is a tibiotarsal bone disorder of rapid growing poultry species. The complete pathogenicity of TD remains unknown; therefore, a study was conducted to screen possible role of proliferation-related gene expression in thiram-induced tibial TD chickens. Materials and Methods. Three hundred sixty ( n = 360 ) broiler chickens were equally divided into control (C) and thiram (T) groups. Furthermore, the C and T groups were dividedinto 8-, 9-, 11-, and 13-day-old chickens. Results. Clinically, it was observed that broiler chickens of group T had abnormal posture, gait, and lameness, and histopathological results revealed dead and abnormal chondrocytes of T group on day 6. Real-time qPCR results showed that HDAC1, MTA1, H4, and PCNA genes were significantly expressed ( P < 0.05 ). HDAC1 was upregulated on days 1, 2, 4, and 6 ( P < 0.01 ); MTA1 was upregulated on days 1 and 2 ( P < 0.01 ); H4 was upregulated on days 2 and 4 ( P < 0.01 ), and PCNA was downregulated on days 1, 2, and 4 ( P < 0.01 ). Furthermore, IHC results of HDAC1 protein were significantly ( P < 0.01 ) expressed in proliferative zone of day 1 and hypertrophic zone of day 6. MTA1 protein was significantly ( P < 0.01 ) expressed on days 1, 2, and 6 in all zones, except prehypertrophic zone of day 2. Conclusion. In conclusion, the mRNA expressions of HDAC1, MTA1, H4, and PCNA were differentially expressed in the chondrocytes of thiram-induced TD chickens. HDAC1 and MTA1 protein expression found involved and responsible in the abnormal chondrocytes’ proliferation of broiler chicken.
Published: 2022
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9. Generation of a live attenuated influenza A vaccine by proteolysis targeting

Author: Longlong Si, Quan Shen, Jing Li, Li Chen, Jinying Shen, Xue Xiao, Haiqing Bai, Tang Feng, Adam Yongxin Ye, Le Li, Chunhe Zhang, Zhen Li, Ping Wang, Crystal Yuri Oh, Atiq Nurani, Siwen Niu, Chengxin Zhang, Xiaoqiong Wei, Wanqiong Yuan, Hao Liao, Xiaojie Huang, Ning Wang, Wen-xia Tian, Hongwei Tian, Li Li, Xiaoheng Liu, and Roberto Plebani
Subjects: Proteasome Endopeptidase Complex, Ferrets, Biomedical Engineering, Bioengineering, Vaccines, Attenuated, Applied Microbiology and Biotechnology, Mice, Orthomyxoviridae Infections, Influenza Vaccines, Influenza, Human, Proteolysis, Animals, Humans, Molecular Medicine, Biotechnology
Abstract: The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin-proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines.
Published: 2022
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10. Perioperative active warming strategies in children: a protocol for a multicentre, prospective, randomized controlled trial

Author: Qiao, Lanxin, Wang, Yaxin, Liang, Yi, Xia, Tian, Li, Ling, Xiong, Wei, Liu, Bin, Feng, Yifan, Liu, Yan, Jin, Xu, and Zhang, Jianmin
Subjects: Pediatrics, Perinatology and Child Health
Published: 2023
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11. High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis in ALK-Rearranged Non-Small Cell Lung Cancer

Author: Tian, Xia Tian, Yalun Li, Qin Huang, Hao Zeng, Qi Wei, and Panwen
Subjects: ALK, PD-L1, tumour-immune microenvironment, multiplex immunofluorescence, non-small cell lung cancer
Abstract: High tumour programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) after tyrosine kinase inhibitor (TKI) therapy in ALK-rearranged non-small cell lung cancer (NSCLC). However, the characteristics of the tumour microenvironment (TME) and their prognostic values in ALK-rearranged NSCLC are unknown. Here, we collected tumour tissues from pretreated ALK-rearranged NSCLC patients, immunohistochemical staining was used to assess PD-L1 expression, and tumour-infiltrating immune cells were determined via multiplex immunofluorescence staining (mIF). Our data showed that the median values of PFS for the high PD-L1 group and low PD-L1 group who received ALK-TKI treatment were 4.4 and 16.4 months, respectively (p = 0.008). The median overall survival (OS) of the two groups was 24.0 months and not reached, respectively (p = 0.021). Via univariate and multivariate analyses, a high PD-L1 expression and a worse ECOG PS were determined to be independent prognostic factors of OS (HR = 3.35, 95% CI: 1.23–9.11, p = 0.018; HR = 6.42, 95% CI: 1.45–28.44, p = 0.014, respectively). In addition, the high PD-L1 group had increased Tregs and exhausted CD8+ T cells in both the tumour and stroma (all p < 0.05). High PD-L1 expression was an adverse predictive and prognostic biomarker for ALK-rearranged NSCLC. The characteristics of the TME in patients with high PD-L1 expression were shown to have an immunosuppressive status.
Published: 2023
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12. Cooperative IoT Data Sharing with Heterogeneity of Participants Based on Electricity Retail

Author: Wang, Bohong, Guo, Qinglai, Xia, Tian, Li, Qiang, Liu, Di, and Zhao, Feng
Subjects: FOS: Electrical engineering, electronic engineering, information engineering, Systems and Control (eess.SY), Electrical Engineering and Systems Science - Systems and Control
Abstract: With the development of Internet of Things (IoT) and big data technology, the data value is increasingly explored in multiple practical scenarios, including electricity transactions. However, the isolation of IoT data among several entities makes it difficult to achieve optimal allocation of data resources and convert data resources into real economic value, thus it is necessary to introduce the IoT data sharing mode to drive data circulation. To enhance the accuracy and fairness of IoT data sharing, the heterogeneity of participants is sufficiently considered, and data valuation and profit allocation in IoT data sharing are improved based on the background of electricity retail. Data valuation is supposed to be relevant to attributes of IoT data buyers, thus risk preferences of electricity retailers are applied as characteristic attributes and data premium rates are proposed to modify data value rates. Profit allocation should measure the marginal contribution shares of electricity retailers and data brokers fairly, thus asymmetric Nash bargaining model is used to guarantee that they could receive reasonable profits based on their specific contribution to the coalition of IoT data sharing. Considering the heterogeneity of participants comprehensively, the proposed IoT data sharing fits for a large coalition of IoT data sharing with multiple electricity retailers and data brokers. Finally, to demonstrate the applications of IoT data sharing in smart grids, case studies are utilized to validate the results of data value for electricity retailers with different risk preferences and the efficiency of profit allocation using asymmetric Nash bargaining model., 18 pages, 14 figures
Published: 2023

13. The Global Spread Pattern of Rat Lungworm Based on Mitochondrial Genetics

Author: Lv, Xia Tian, Shen Chen, Lei Duan, Yingjun Qian, Hongmei Li, and Shan
Subjects: Angiostrongylus cantonensis, Angiostrongylus mackerrasae, Angiostrongylus malaysiensis, rat lungworm, mitochondrial gene, distribution, phylogeny
Abstract: Eosinophilic meningitis due to rat lungworm, Angiostrongylus cantonensis, is a global public health concern. Human cases and outbreaks have occurred in the new endemic areas, including South America and Spain. The growing genetic data of A. cantonensis provides a unique opportunity to explore the global spread pattern of the parasite. Eight more mitochondrial (mt) genomes were sequenced by the present study. The phylogeny of A. cantonensis by Bayesian inference showed six clades (I–VI) determined by network analysis. A total of 554 mt genomes or fragments, which represented 1472 specimens of rat lungworms globally, were used in the present study. We characterized the gene types by mapping a variety of mt gene fragments to the known complete mt genomes. Six more clades (I2, II2, III2, V2, VII and VIII) were determined by network analysis in the phylogenies of cox1 and cytb genes. The global distribution of gene types was visualized. It was found that the haplotype diversity of A. cantonensis in Southeast and East Asia was significantly higher than that in other regions. The majority (78/81) of samples beyond Southeast and East Asia belongs to Clade II. The new world showed a higher diversity of Clade II in contrast with the Pacific. We speculate that rat lungworm was introduced from Southeast Asia rather than the Pacific. Therefore, systematic research should be conducted on rat lungworm at a global level in order to reveal the scenarios of spread.
Published: 2023
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14. The transcription factor BnaWRKY10 regulates cytokinin dehydrogenase BnaCKX2 to control cytokinin distribution and seed size in Brassica napus

Author: Guanbo Yan, Sijia Li, Mengya Ma, Chengtao Quan, Xia Tian, Jinxing Tu, Jinxiong Shen, Bin Yi, Tingdong Fu, Chaozhi Ma, Liang Guo, and Cheng Dai
Subjects: Physiology, Plant Science
Abstract: Cytokinins (CKs) are the phytohormones that promote cell division and differentiation. However, the regulation of CKs distribution and homeostasis in Brassica napus is poorly understood. Here, the endogenous CKs were first quantified by LC-ESI-MS/MS in rapeseed tissues and visualized by TCSn::GUS reporter lines. Interestingly, the cytokinin oxidase/dehydrogenase BnaCKX2 homologs were mainly expressed in reproductive organs. Later, the quadruple mutants of the four BnaCKX2 homologs were generated. Endogenous CKs were increased in the seeds of the BnaCKX2 quadruple mutants, resulting in a significantly reduced seed size. In contrast, overexpression of BnaA9.CKX2 resulted in larger seeds, probably by delaying endosperm cellularization. Furthermore, BnaC6.WRKY10b, but not BnaC6.WRKY10a, positively regulated BnaA9.CKX2 expression by binding directly to its promoter region. Overexpression of BnaC6.WRKY10b rather than BnaC6.WRKY10a resulted in lower CKs levels and larger seeds by activating BnaA9.CKX2 expression, indicating that the functional differentiation of BnaWRKY10 homologs might have occurred during the B. napus evolution or domestication. Notably, the haploid types of BnaA9.CKX2 were associated with 1000-seed weight in the natural B. napus population. Overall, the study reveals the distribution of CKs in B. napus tissues, and highlights that the BnaWRKY10-mediated BnaCKX2 expression is essential for seed size regulation, providing promising targets for oil crop improvement.
Published: 2023
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15. The preoperative triglyceride-glucose index has a positive effect on predicting the risk of short-term restenosis after carotid artery stenting: a retrospective cohort study

Author: Shan-shan Zhao, Zhen-zhen Jiang, Bo Wei, Jian-bo Zhu, and Xia-tian Liu
Subjects: Neurology, Neurology (clinical)
Abstract: BackgroundIncreasing evidence suggests that insulin resistance is linked to cardiovascular disease and atherosclerosis. The triglyceride–glucose (TyG) index has proven to be a convincing marker to quantitatively evaluate insulin resistance. However, there is no relevant information about the relationship between the TyG index and restenosis after carotid artery stenting.MethodsA total of 218 patients were enrolled. Carotid ultrasound and computed tomography angiography were used to evaluate in-stent restenosis. A Kaplan–Meier analysis and Cox regression method were performed to analyze the correlation between TyG index and restenosis. Schoenfeld residuals were used to determine the proportional-hazards assumption. A restricted cubic spline method was used to model and visualize the dose–response relationship between the TyG index and the risk of in-stent restenosis. Subgroup analysis was also performed.ResultsThirty-one participants (14.2%) developed restenosis. The preoperative TyG index had a time-varying effect on restenosis. Within 29 months post-surgery, an increasing preoperative TyG index was linked to a significant increased risk of restenosis (hazard ratio: 4.347; 95% confidence interval 1.886–10.023). However, after 29 months, the effect was decreased, although not statistically significant. The subgroup analysis showed that the hazard ratios tended to be higher in the age ≤ 71 years subgroup (p p ConclusionThe preoperative TyG index was significantly associated with the risk of short-term restenosis after CAS within 29 months post-surgery. The TyG index may be employed to stratify patients based on their risk of restenosis after carotid artery stenting.
Published: 2023
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16. Prognostic features and comprehensive genomic analysis of <scp> NF1 </scp> mutations in <scp> EGFR </scp> mutant lung cancer patients

Author: Hong‐xia Tian, Zhi‐hong Chen, Guang‐Ling Jie, Zhen Wang, Hong‐hong Yan, Si‐pei Wu, Shui‐lian Zhang, Dan‐xia Lu, Xu‐chao Zhang, and Yi‐long Wu
Subjects: Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging
Abstract: NF1 is a tumor suppressor gene that encodes the neurofibromin protein and negatively regulates Ras signaling. This study was aimed to investigate the molecular, clinical characteristics, and prognostic features of NF1 gene in EGFR mutant lung cancer patients.The next-generation sequencing (NGS) was used to analyze the data from lung cancer patients in the Guangdong Lung Cancer Institute (GLCI) from June 2016 to December 2020.Somatic NF1 mutations were present in 4.2% (135/3220) of Chinese lung cancer patients. NF1 mutations where clearly enriched in older (p 0.001), male (p 0.001), and smoking (p 0.001) patients. Patients with NF1 mutations were more likely to have TP53 (p = 0.003), BRAF (p = 0.001) and RASA1 (p = 0.026) mutations and mutually exclusive with EGFR mutations (p = 0.006). TP53 mutation had worsen prognosis in cases of NF1 mutant (p = 0.026) or EGFR/NF1 co-mutant (p = 0.031) lung adenocarcinomas (LUAD) patients. There was no effect on overall survival (OS) in LUAD patients with and without NF1 mutations, even in LUAD driver-gene negative patients. NF1/EGFR co-mutation patients had a longer OS than a single mutation of either the EGFR gene (median OS: 47.7 m vs. 30.2 m, hazard ratio [95% CI], 0.47 [0.30-0.74], p = 0.004) or NF1 gene (47.7 m vs. 19.0 m, 0.44 [0.27-0.73], p = 0.003). Furthermore, NF1 mutations significantly prolonged OS in EGFR mutant/TP53 wild-type LUAD patients (106.5 m vs. 25.5 m, 0.28 [0.13-0.59], p = 0.003) but not in patients with EGFR/TP53 co-mutations (36.8 m vs. 30.2 m, 0.70 [0.39-1.26], p = 0.280).Our results indicated NF1 mutations served as a good prognostic factor in EGFR mutant/TP53 wild-type lung cancer patients in this single-center study. TP53 mutation was obviously enriched in NF1 mutant patients and had shorter OS.
Published: 2022
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17. Effect of Dry Soil Aggregate Size on Microplastic Distribution and Its Implications for Microplastic Emissions Induced by Wind Erosion

Author: Meiniu Yang, Xia Tian, Zhongling Guo, Chunping Chang, Jifeng Li, Zixiao Guo, Huiru Li, Ruijuan Liu, Rende Wang, Qing Li, and Xueyong Zou
Subjects: Ecology, Health, Toxicology and Mutagenesis, Environmental Chemistry, Pollution, Waste Management and Disposal, Water Science and Technology
Published: 2022
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18. Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF

Author: Yan‐Ting Zhou, Yu‐Qing Yu, Hui Yang, Han Yang, Yan‐Fei Huo, Yang Huang, Xin‐Xia Tian, and Wei‐Gang Fang
Subjects: Mice, Cancer Research, Adenosine Triphosphate, Neovascularization, Pathologic, Oncology, Connective Tissue Growth Factor, Animals, Endothelial Cells, Humans, Triple Negative Breast Neoplasms, General Medicine, Up-Regulation
Abstract: Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple-negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2--YAP-CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM-1 on ECs. Both apyrase (ATP-diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.
Published: 2022
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19. Water-soluble chitosan and phytoremediation efficiency of two Brassica napus L. cultivars in cadmium-contaminated farmland soils

Author: Bian, Jian-Lin, Cao, Wei, Guo, Jun-Mei, Yang, Jun-Xing, Wang, Xue-Dong, Wang, Jie, Huang, Jun, Xia, Tian-Xiang, and Xia, Cun-Yan
Subjects: Environmental Chemistry, Plant Science, Pollution
Abstract: Pot and field trials were conducted to investigate Cd uptake and phytoremediation efficiency of two Brassica napus cultivars (QY-1 and SYH) with applied water-soluble chitosan (WSC, Pot: 0, 2% and 4%; Field: 0 and 10 g·m−2) grown in Cd-contaminated soils. The results from the pot and field trials generally showed that WSC treatments significantly increased Cd concentrations in shoot and root tissues by 33.77–159.71% (except for SYH/JY) and 7.42–168.71% of two B. napus cultivars compared with the control (p < 0.05). The uptake of Cd by shoots of SYH was obviously higher than by shoots of QY-1 treated with WSC under pot and field conditions, which was 1.54–2.22 times than that of QY-1 (p < 0.05). The results indicated that 2% WSC treatment significantly increased the water-soluble and acid extractable Cd in rhizosphere soils of both B. napus cultivars. Furthermore, Cd concentrations in the oils of two B. napus cultivars with applied WSC (10 g·m−2) grown under field conditions were not significantly different from commercial rapeseed oils. Rapeseed oil of B. napus is not only an edible oil with high nutritional value, but it can also be converted into biomass diesel that can be used as a substitute for petroleum diesel.
Published: 2022
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20. A deep learning-based system for real-time image reporting during esophagogastroduodenoscopy: a multicenter study

Author: Lianlian Wu, Zehua Dong, Ganggang Mu, Wei Zhou, Yanxia Li, Zhaohong Shi, Xia Tian, Song Liu, Qingxi Zhu, Renduo Shang, Mengjiao Zhang, Lihui Zhang, Ming Xu, Yijie Zhu, Xiao Tao, Tingting Chen, Xun Li, Chenxia Zhang, Xinqi He, Jing Wang, Renquan Luo, Hongliu Du, Yutong Bai, Liping Ye, and Honggang Yu
Subjects: Gastroenterology
Abstract: Background and study aims Endoscopic reports are essential for the diagnosis and follow-up of gastrointestinal diseases. This study aimed to construct an intelligent system for automatic photo documentation during esophagogastroduodenoscopy (EGD) and test its utility in clinical practice. Patients and methods Seven convolutional neural networks trained and tested using 210,198 images were integrated to construct the endoscopic automatic image reporting system (EAIRS). We tested its performance through man-machine comparison at three levels: internal, external, and prospective test. Between May 2021 and June 2021, patients undergoing EGD at Renmin Hospital of Wuhan University were recruited. The primary outcomes were accuracy for capturing anatomical landmarks, completeness for capturing anatomical landmarks, and detected lesions. Results The EAIRS outperformed endoscopists in retrospective internal and external test. A total of 161 consecutive patients were enrolled in the prospective test. The EAIRS achieved an accuracy of 95.2% in capturing anatomical landmarks in the prospective test. It also achieved higher completeness on capturing anatomical landmarks compared with endoscopists: (93.1% vs. 88.8%), and was comparable to endoscopists on capturing detected lesions: (99.0% vs. 98.0%). Conclusions The EAIRS can generate qualified image reports and could be a powerful tool for generating endoscopic reports in clinical practice.
Published: 2022
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21. Photocatalyst-, metal- and additive-free regioselective radical cascade sulfonylation/cyclization of benzimidazole derivatives with sulfonyl chlorides induced by visible light

Author: Bin Sun, Hai-Xia Tian, Zhi-Gang Ni, Pan-Yi Huang, Hao Ding, Bing-Qian Li, Can Jin, Chun-Lei Wu, and Run-Pu Shen
Subjects: Organic Chemistry
Abstract: An environmentally friendly and practical protocol for the visible-light-triggered regioselective radical cascade sulfonylation/cyclization of unactivated alkenes towards the synthesis of polycyclic benzimidazoles containing the sulfone group has been developed.
Published: 2022
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22. Effective removal of Cd(<scp>ii</scp>) by sludge biochar supported nanoscale zero-valent iron from aqueous solution: characterization, adsorption properties and mechanism

Author: Liang Dai, Tao Han, Gui Ma, Xia Tian, Kai Meng, Zhenle Lei, and Jun Ren
Subjects: Materials Chemistry, General Chemistry, Catalysis
Abstract: Nanoscale zero-valent iron (nZVI) has a high chemical reactivity for heavy metals, but it forms aggregates easily.
Published: 2022
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23. Efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis

Author: Ying Li, Na Gao, Qun Huang, Xia Tian, Min Zhao, and Xue-Li Zeng
Subjects: Ophthalmology, blood stasis, genetic structures, non-proliferative diabetic retinopathy, visual function, RE1-994, buyang huanwu decoction, qi-yin deficiency
Abstract: AIM: To observe the efficacy of addition and subtraction of Buyang Huanwu decoction in the adjuvant treatment of non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis and its effects on traditional Chinese medicine(TCM)syndromes and visual function level. METHODS: A total of 110 patients with non-proliferative diabetic retinopathy of Qi-Yin deficiency and blood stasis in our hospital between January 2017 and December 2019 were selected and divided into observation group(55 cases, 110 eyes)and control group(55 cases, 110 eyes). Patients in control group received conventional treatment according to the condition of patients with reference to relevant guidelines, and patients in observation group were combined with addition and subtraction of Buyang Huanwu decoction adjuvant therapy on this basis. The clinical efficacy after 3mo of treatment, and TCM syndromes scores, clinical indicators(macular edema score, macular retinal volume, macular foveal retinal thickness), visual function(best corrected visual acuity, average visual field sensitivity)and serum biochemical indicators [vascular endothelial growth factor(VEGF), hypoxia-inducible factor-1(HIF-1)] before treatment and 3mo after treatment were compared between the two groups.RESULTS: After 3mo of treatment, the total effective rate of treatment in observation group was significantly higher than that in control group(P
Published: 2022

24. Supplementary Figure 2 from Lung Cancers with Concomitant EGFR Mutations and ALK Rearrangements: Diverse Responses to EGFR-TKI and Crizotinib in Relation to Diverse Receptors Phosphorylation

Author: Yi-Long Wu, Tony S. Mok, Ri-Qiang Liao, Qiang Nie, Wen-Zhao Zhong, Xue-Ning Yang, Bin-Chao Wang, Zhen Wang, Ben-Yuan Jiang, Yi-Sheng Huang, Hua-Jun Chen, Zhi Xie, Hong-Xia Tian, Qing Zhou, Chong-Rui Xu, Jian Su, Xu-Chao Zhang, and Jin-Ji Yang
Abstract: PDF file - 253KB, Representative IHC graphs of EGFR, p-EGFR, ALK, p-ALK in EGFR-mutant/ALK-negative, EGFR-WT/ALK-positive tumors, and EGFR-WT/ALK-negative tumors.
Published: 2023
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25. Data from Lung Cancers with Concomitant EGFR Mutations and ALK Rearrangements: Diverse Responses to EGFR-TKI and Crizotinib in Relation to Diverse Receptors Phosphorylation

Author: Yi-Long Wu, Tony S. Mok, Ri-Qiang Liao, Qiang Nie, Wen-Zhao Zhong, Xue-Ning Yang, Bin-Chao Wang, Zhen Wang, Ben-Yuan Jiang, Yi-Sheng Huang, Hua-Jun Chen, Zhi Xie, Hong-Xia Tian, Qing Zhou, Chong-Rui Xu, Jian Su, Xu-Chao Zhang, and Jin-Ji Yang
Abstract: Purpose: We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non–small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors.Experimental Design: We screened 977 consecutive patients with NSCLC for the presence of concomitant EGFR mutations and ALK rearrangements by rapid amplification of cDNA ends-coupled PCR sequencing and FISH. Immunohistochemistry (IHC) and Western blotting were used to correlate the activation of EGFR, ALK, and downstream proteins with responses to EGFR-TKIs and crizotinib.Results: The overall frequency of concomitant EGFR mutations and ALK rearrangements was 1.3% (13/977). EGFR/ALK co-alterations were found in 3.9% (13/336) EGFR-mutant and 18.6% (13/70) ALK-rearranged patients. Ten tumors were treated with first-line EGFR-TKIs, with a response rate of 80% (8/10). Two tumors with high phospho-ALK levels and low phospho-EGFR levels achieved stable and progressive disease, respectively. Median progression-free survival was 11.2 months. Coexpression of mutant EGFR and ALK fusion proteins in the same tumor cell populations was detected by IHC. Two cases with high phospho-ALK levels treated with crizotinib achieved partial responses; two cases with low phospho-ALK levels had progressive or stable disease.Conclusion:ALK rearrangements and EGFR mutations could coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib. Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib. Clin Cancer Res; 20(5); 1383–92. ©2014 AACR.
Published: 2023
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26. Supplementary Figure Legends from Lung Cancers with Concomitant EGFR Mutations and ALK Rearrangements: Diverse Responses to EGFR-TKI and Crizotinib in Relation to Diverse Receptors Phosphorylation

Author: Yi-Long Wu, Tony S. Mok, Ri-Qiang Liao, Qiang Nie, Wen-Zhao Zhong, Xue-Ning Yang, Bin-Chao Wang, Zhen Wang, Ben-Yuan Jiang, Yi-Sheng Huang, Hua-Jun Chen, Zhi Xie, Hong-Xia Tian, Qing Zhou, Chong-Rui Xu, Jian Su, Xu-Chao Zhang, and Jin-Ji Yang
Abstract: PDF file - 63KB.
Published: 2023
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27. Supplementary Figure 1 from Lung Cancers with Concomitant EGFR Mutations and ALK Rearrangements: Diverse Responses to EGFR-TKI and Crizotinib in Relation to Diverse Receptors Phosphorylation

Author: Yi-Long Wu, Tony S. Mok, Ri-Qiang Liao, Qiang Nie, Wen-Zhao Zhong, Xue-Ning Yang, Bin-Chao Wang, Zhen Wang, Ben-Yuan Jiang, Yi-Sheng Huang, Hua-Jun Chen, Zhi Xie, Hong-Xia Tian, Qing Zhou, Chong-Rui Xu, Jian Su, Xu-Chao Zhang, and Jin-Ji Yang
Abstract: PDF file - 635KB, Sequence results of EML4-ALK fusion variants.
Published: 2023
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28. LncRNA LOC105369504 inhibits tumor proliferation and metastasis in colorectal cancer by regulating PSPC1

Author: Ting Zhan, Xueting Cheng, Qingxi Zhu, Zheng Han, Kejing Zhu, Jie Tan, Men Liu, Wei Chen, Xiaoli Chen, Xiaohong Chen, Xia Tian, and Xiaodong Huang
Subjects: Cancer Research, Cellular and Molecular Neuroscience, Immunology, Cell Biology
Abstract: There is growing evidence that long non-coding RNAs (lncRNAs) are significant contributors to the epigenetic mechanisms implicated in the emergence, progression and metastasis of the colorectal cancer (CRC), but many remain underexplored. A novel lncRNA LOC105369504, was identified to be a potential functional lncRNA by microarray analysis. In CRC, the expression of LOC105369504 was markedly decreased and resulted in distinct variations in proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vivo and in vitro. This study showed that LOC105369504 bound to the protein of paraspeckles compound 1 (PSPC1) directly and regulated its stability using the ubiquitin-proteasome pathway in CRC cells. The suppression of CRC by LOC105369504 could be reversed through PSPC1 overexpression.This study showed that in CRC, LOC105369504 was under-regulated and as a novel lncRNA, LOC105369504 exerted tumor suppressive activity to suppress the proliferation together with metastasis in CRC cells through the regulation of PSPC1. These results offer new perspectives on the lncRNA effect on the progression of CRC.
Published: 2023
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29. Baseline vessel wall magnetic resonance imaging characteristics associated with in-stent restenosis for intracranial atherosclerotic stenosis

Author: Bing Tian, Chengcheng Zhu, Xia Tian, Qinqin Kang, Chengwei Shao, Mahmud Mossa-Basha, Jianping Lu, and David A Saloner
Subjects: Pathologic, Assistive Technology, Clinical Trials and Supportive Activities, Bioengineering, General Medicine, Intracranial Arteriosclerosis, Cardiovascular, Atherosclerosis, Constriction, Magnetic Resonance Imaging, stroke, Coronary Restenosis, vessel wall, Cross-Sectional Studies, Heart Disease, Clinical Research, Humans, Biomedical Imaging, Surgery, stent, Neurology (clinical), Magnetic Resonance Angiography, Plaque, Atherosclerotic
Abstract: BackgroundImaging factors, specifically baseline plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) that could be associated with in-stent restenosis (ISR), are still unknown. We aimed to investigate the presenting clinical and plaque features on HR-VWI associated with ISR.MethodsSixty-four patients with intracranial stent placement for intracranial atherosclerotic stenosis who had pre- and post-contrast T1-weighted HR-VWI on 3.0T prior to stenting were included in this analysis. Student's t-test, Mann–Whitney U test, χ2 test, or the Cochran–Mantel–Haenszel (CMH) test were used to compare clinical and baseline HR-VWI characteristics of the patients between the ISR and non-ISR groups. Univariable and multivariable logistic analysis were used to test the clinical and imaging factors associated with ISR.ResultsAmong the 64 patients, 9 patients (14.06%) developed ISR during the 2-year follow-up period. Plaque burden (median 0.89 vs 0.92, P=0.04), minimum lumen area (0.009 cm2vs 0.006 cm2, P=0.04), plaque eccentricity (55.6% vs 89.1%, P＜0.01), enhancement ratio (1.36 vs 0.84, P＜0.01), and enhancement involvement (type 2 represents ≥50% cross-sectional wall involvement; 100% vs 63.6%, P=0.03) all significantly differed between patients with and without ISR. Multivariable analysis revealed that lower frequency of plaque eccentricity (OR 0.18, 95% CI 0.04 to 0.96, P=0.04) and higher enhancement ratio (OR 3.57, 95% CI 1.02 to 12.48, P=0.04) were independently associated with ISR.ConclusionsPreliminary findings showed that ISR was independently associated with plaque concentricity and higher enhancement ratios on pre-stenting HR-VWI for patients with symptomatic intracranial atherosclerotic stenosis.
Published: 2023

30. Ultrastructure and distribution of antennal sensilla of Bombus terrestris (Hymenoptera: Apidae)

Author: Xi Huang, Xi-lian Xu, Ru-xu Li, Su Wang, and Li-xia Tian
Subjects: Animal Science and Zoology, Biodiversity, Taxonomy
Abstract: Huang, Xi, Xu, Xi-lian, Li, Ru-xu, Wang, Su, Tian, Li-xia (2023): Ultrastructure and distribution of antennal sensilla of Bombus terrestris (Hymenoptera: Apidae). Zoologischer Anzeiger 302: 239-247, DOI: 10.1016/j.jcz.2022.12.006, URL: http://dx.doi.org/10.1016/j.jcz.2022.12.006
Published: 2023

31. Impact of atrazine on the dynamic response of Daphnia pulex populations to fish predation risk

Author: Qin, Shanshan, Xia, Tian, Li, Gongzheng, Gu, Lei, Sun, Yunfei, and Yang, Zhou
Subjects: Ecology, Ecology, Evolution, Behavior and Systematics
Abstract: Herbicide pollution is persistent, which not only has a negative impact on individual organisms, but also may alter population dynamics and stability of interspecific relationships. Cladocerans, an important part of zooplankton, are often simultaneously exposed to environmental pollutants and predation risk in the aquatic environment. To evaluate the combined effects of atrazine and fish predation risk on the population traits of cladocerans, we exposed Daphnia pulex to different concentrations of atrazine (0, 0.05, 0.10, and 1.0 mg L−1) with or without fish (Rhodeus ocellatus) kairomone, recorded the key population traits, and fitted Gaussian model to population dynamics. Results showed that fish kairomone increased the population density at the end of the experiment and resting eggs production, and tended to decrease the total biomass and the average dry weight per individual of D. pulex. Atrazine reduced the total biomass, the average dry weight per individual, and resting eggs production of D. pulex populations. Atrazine also decreased the population density at the end of the experiment of D. pulex in fish kairomone treatment, and attenuated the promoting effect of fish kairomone on resting eggs production and the reduction of the total biomass. The findings highlighted the importance of considering the combined impact of environmental pollutants and predation risks on zooplankton populations.
Published: 2023
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32. In Situ‐Generated Cu I Catalytic System for Oxidative N ‐Formylation of N‐Heterocycles and Acyclic Amines with Methanol

Author: Yujing Zhang, Xingchao Dai, Jixue Wang, Junxi Liang, Jabor Rabeah, Xia Tian, Xiaoqiang Yao, Yanbin Wang, and Shaofeng Pang
Subjects: General Energy, General Chemical Engineering, Environmental Chemistry, General Materials Science
Abstract: The development of a sustainable and simple catalytic system for N-formylation of N-heterocycles with methanol via direct coupling strategy remains a challenge, owing to the competition of many side reactions in view of the sensitive of N-heterocycles to many catalytic oxidation or dehydrogenation systems. In this work, in situ generated Cu(I) catalytic system for oxidative N-formylation of N-heterocycles with methanol that is based on the case study of a more typical 1,2,3,4-tetrahydroquinoline as substrate has been described. Not just N-heterocycles, some normal amines are also successfully transformed into the corresponding N-formamides in moderate yields. Furthermore, a probable reaction mechanism and reaction pathway have been proposed, and extension of work based on some findings leads to a demonstration that the formed •O2- and •OOH radicals in the catalytic system is related to the formation of undesired tarlike products.
Published: 2023
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33. Longitudinal Plasma Proteomics-Derived Biomarkers Predict Response to MET Inhibitors for MET-Dysregulated NSCLC

Author: Guang-Ling Jie, Lun-Xi Peng, Mei-Mei Zheng, Hao Sun, Song-Rong Wang, Si-Yang Maggie Liu, Kai Yin, Zhi-Hong Chen, Hong-Xia Tian, Jin-Ji Yang, Xu-Chao Zhang, Hai-Yan Tu, Qing Zhou, Catherine C. L. Wong, and Yi-Long Wu
Subjects: Cancer Research, Oncology, Non-small cell lung cancer, MET dysregulation, proteomics, MET inhibitor, biomarker
Abstract: MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients treated with MET inhibitors using mass spectrometry. We analyzed the plasma proteomics from patients with MET dysregulation (including MET amplification and MET overexpression) treated with MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 plasma samples were included. We classified patients into the PD group and non-PD group based on clinical response. The baseline proteomic profiles of patients in the PD group were distinct from those in the non-PD group. Through protein screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) could predict the efficacy of patients treated with MET inhibitors, with an area under the curve (AUC) of 0.93, better than conventional fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining the four-protein signature with FISH or IHC test could also reach higher predictive performance. Further, the combined signature could predict progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also validated the performance of the four-protein signature in another cohort of plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a substitutable or complementary role to conventional MET FISH or IHC tests. This exploration will help select patients who may benefit from MET inhibitors.
Published: 2023
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34. An input-output framework for stability and synchronization analysis of networks of infinite-dimensional linear systems

Author: Xia, Tian and Scardovi, Luca
Subjects: Optimization and Control (math.OC), 93A14, 93C05, 93C20, FOS: Mathematics, Mathematics - Optimization and Control
Abstract: This paper extends a synchronization criterion established for networks of finite-dimensional linear systems to the infinite-dimensional setting. Our result, established in the general framework of input-output relations, requires an additional input-output stability property, compared to the finite-dimensional counterpart. We establish conditions for this property to hold for a large class of infinite-dimensional systems including Abstract Cauchy Problems, parabolic PDEs, and time-delay ordinary differential equations.
Published: 2023
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35. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author: Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo 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Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
Published: 2023
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36. Additional file 1 of Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor

Author: Ning, Bo, Huang, Peng, Zhu, Lining, Ma, Zhijie, Chen, Xiaoli, Xu, Haojun, Ma, Ruixue, Yao, Chengyun, Zheng, Pengfei, Xia, Tian, and Xia, Hongping
Abstract: Additional file 1.
Published: 2023
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37. Combined burden and functional impact tests for cancer driver discovery using DriverPower

Author: Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, 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Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
Published: 2023
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38. High Fidelity Image Counterfactuals with Probabilistic Causal Models

Author: Ribeiro, Fabio De Sousa, Xia, Tian, Monteiro, Miguel, Pawlowski, Nick, and Glocker, Ben
Subjects: Methodology (stat.ME), FOS: Computer and information sciences, Computer Science - Machine Learning, Statistics - Methodology, Machine Learning (cs.LG)
Abstract: We present a general causal generative modelling framework for accurate estimation of high fidelity image counterfactuals with deep structural causal models. Estimation of interventional and counterfactual queries for high-dimensional structured variables, such as images, remains a challenging task. We leverage ideas from causal mediation analysis and advances in generative modelling to design new deep causal mechanisms for structured variables in causal models. Our experiments demonstrate that our proposed mechanisms are capable of accurate abduction and estimation of direct, indirect and total effects as measured by axiomatic soundness of counterfactuals., Comment: ICML2023 publication
Published: 2023
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39. Integrative pathway enrichment analysis of multivariate omics data

Author: Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Reimand, Jüri, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De 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Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grimmond, Sean M, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Haider, Syed, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Han, Leng, Hanna, George B, Hansmann, Martin, Harismendy, Olivier, Harliwong, Ivon, Harrington, Eoghan, 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Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Junjun, Zhang, Xiuqing, Zhang, Zemin, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, and Veer, L van’t
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
Published: 2023
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40. Pathway and network analysis of more than 2500 whole cancer genomes

Author: Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kellis, Manolis, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pons, Tirso, Reyes-Salazar, Iker, Rheinbay, Esther, Rubio-Perez, Carlota, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, 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Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ossowski, Stephan, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Peter J, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pearson, John V, Pedamallu, Chandra Sekhar, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Puiggròs, Montserrat, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reis-Filho, Jorge, Reuter, Victor, Reynolds, Sheila M, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Rippe, Karsten, Roach, Jeffrey, Roberts, Lewis R, Roberts, Nicola D, Roberts, Steven A, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodriguez-Martin, Bernardo, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Saini, Natalie, Saito-Adachi, Mihoko, Salcedo, Adriana, Salgado, Roberto, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shelton, Troy, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shringarpure, Suyash S, Shriver, Craig, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warren, Anne Y, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Junjun, Zhang, Xiuqing, Zhang, Zemin, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, and Veer, L van’t
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
Published: 2023
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41. Distributionally robust chance constrained Markov decision process with Kullback-Leibler divergence

Author: Xia, Tian, Liu, Jia, and Lisser, Abdel
Subjects: Optimization and Control (math.OC), FOS: Mathematics, 90C40, Mathematics - Optimization and Control
Abstract: This paper considers the distributionally robust chance constrained Markov decision process with random reward and ambiguous reward distribution. We consider individual and joint chance constraint cases with Kullback-Leibler divergence based ambiguity sets centered at elliptical distributions or elliptical mixture distributions, respectively. We derive tractable reformulations of the distributionally robust individual chance constrained Markov decision process problems and design a new hybrid algorithm based on the sequential convex approximation and line search method for the joint case. We carry out numerical tests with a machine replacement problem.
Published: 2023
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42. Divergent mutational processes distinguish hypoxic and normoxic tumours

Author: Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campbell, Peter J, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, 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James E, Habermann, Nina, Hach, Faraz, Haider, Syed, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Jiao, Wei, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, 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Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Sidiropoulos, Nikos, Siebert, Reiner, Sieuwerts, Anieta M, Sieverling, Lina, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, 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Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
Published: 2023
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43. Additional file 3 of Exosomal circ_0026611 contributes to lymphangiogenesis by reducing PROX1 acetylation and ubiquitination in human lymphatic endothelial cells (HLECs)

Author: Yao, Wenjian, Jia, Xiangbo, Zhu, Li, Xu, Lei, Zhang, Quan, Xia, Tian, and Wei, Li
Abstract: Additional file 3. Original images of western blot and the original image of mass spectrometry in Figure 5A.
Published: 2023
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44. Penalty Gradient Normalization for Generative Adversarial Networks

Author: Xia, Tian
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, Machine Learning (cs.LG)
Abstract: In this paper, we propose a novel normalization method called penalty gradient normalization (PGN) to tackle the training instability of Generative Adversarial Networks (GANs) caused by the sharp gradient space. Unlike existing work such as gradient penalty and spectral normalization, the proposed PGN only imposes a penalty gradient norm constraint on the discriminator function, which increases the capacity of the discriminator. Moreover, the proposed penalty gradient normalization can be applied to different GAN architectures with little modification. Extensive experiments on three datasets show that GANs trained with penalty gradient normalization outperform existing methods in terms of both Frechet Inception and Distance and Inception Score., Comment: Under Review
Published: 2023
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45. A Bayesian phase I–II clinical trial design to find the biological optimal dose on drug combination

Author: Wang, Ziqing, Zhang, Jingyi, Xia, Tian, He, Ruyue, and Yan, Fangrong
Abstract: In recent years, combined therapy shows expected treatment effect as they increase dose intensity, work on multiple targets and benefit more patients for antitumor treatment. However, dose -finding designs for combined therapy face a number of challenges. Therefore, under the framework of phase I–II, we propose a two-stage dose -finding design to identify the biologically optimal dose combination (BODC), defined as the one with the maximum posterior mean utility under acceptable safety. We model the probabilities of toxicity and efficacy by using linear logistic regression models and conduct Bayesian model selection (BMS) procedure to define the most likely pattern of dose–response surface. The BMS can adaptively select the most suitable model during the trial, making the results robust. We investigated the operating characteristics of the proposed design through simulation studies under various practical scenarios and showed that the proposed design is robust and performed well.
Published: 2023
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46. Genomic footprints of activated telomere maintenance mechanisms in cancer

Author: Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio CP, Ossowski, Stephan, Pearson, John V, Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D, Roberts, Steven A, Rodriguez-Martin, Bernardo, Schumacher, Steven E, Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Stewart, Chip, Torrents, David, MC Tubio, Jose, Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A, Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, 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Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
Subjects: Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
Published: 2023
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47. Stereoselective Dehydroxyboration of Allylic Alcohols to Access (E)-Allylboronates by a Combination of C–OH Cleavage and Boron Transfer under Iron Catalysis

Author: Yu-Kun Zhang, Wei Su, Fan Shiming, Xia Tian, Jian-Rong Han, Rui-Xiao Qiao, Ting-Ting Wang, Ya-Xin You, Shouxin Liu, Xiao-Li Zhen, and Qiushi Cheng
Subjects: inorganic chemicals, Allylic rearrangement, Chemistry, organic chemicals, Organic Chemistry, food and beverages, chemistry.chemical_element, Ring (chemistry), Cleavage (embryo), Biochemistry, Medicinal chemistry, Catalysis, SN2 reaction, Stereoselectivity, Physical and Theoretical Chemistry, Boron
Abstract: Iron-catalyzed direct SN2' dehydroxyboration of allylic alcohols has been developed to access (E)-stereoselective allylboronates. Allylic alcohols with diverse structures and functional groups, especially derived from natural products, underwent smooth transformation. The six-membered ring transition state formed by allylic alcohols and iron-boron intermediate was indicated to be the key component involved in transfer of the boron group, activation of the C-OH bond, and control of the stereoselectivity.
Published: 2021
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48. Decorating hole transport material with −CF3 groups for highly efficient and stable perovskite solar cells

Author: Yuan Cai, Sijing Wang, Da Li, Bin Li, Zhike Liu, Kunpeng Guo, Xia Tian, Zhang Zheng, and Xiaozhong Liang
Subjects: Electron mobility, Materials science, Energy conversion efficiency, Energy Engineering and Power Technology, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Fuel Technology, Chemical engineering, Electrochemistry, Alkoxy group, Thermal stability, 0210 nano-technology, Energy (miscellaneous), Perovskite (structure)
Abstract: The hole transport material (HTM) plays an extremely important role to determine the power conversion efficiency (PCE) and the stability of perovskite solar cells (PSCs). Herein, we report an effective strategy to improve the performance of HTMs by introducing −CF3 groups via the rational decorative mode. Upon direct attachment or nonconjugated alkoxyl bridging of −CF3 groups on the terminal diphenylamines, the resulting molecular HTMs, i.e., 2,7-BCzA4CF3 and 2,7-BCzA4OCCF3, show distinct properties. Compared with 2,7-BCzA4CF3, the nonconjugated alkoxyl bridging −CF3 group-based 2,7-BCzA4OCCF3 exhibits better thermal stability, hydrophobicity, and a dramatically upgraded hole mobility by 135.7-fold of magnitude to 1.71 × 10−4 cm2 V−1 S−1. The PSCs with 2,7-BCzA4OCCF3 as HTM exhibit an PCE of up to 20.53% and excellent long-term stability, maintaining 92.57% of their performance for 30 days in air with humidity of 30% without encapsulation. This work provides beneficial guidelines for the design of new HTMs for efficient and stable PSCs.
Published: 2021
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49. Primary mucosal-associated lymphoid tissue extranodal marginal zone lymphoma of the bladder from an imaging perspective: A case report

Author: Yuan-Yuan Zheng, Zhen-Zhen Jiang, Xia-Tian Liu, and Chuan-Ling Hou
Subjects: Pathology, medicine.medical_specialty, business.industry, Bladder, Perspective (graphical), Marginal zone lymphoma, General Medicine, Lymphatic system, immune system diseases, Mucosal-associated lymphoid tissue extranodal marginal zone lymphoma, hemic and lymphatic diseases, Case report, medicine, business, Computed tomography, Ultrasonography
Abstract: BACKGROUND Mucosal-associated lymphoid tissue extranodal marginal zone (MALT) lymphoma is a low-grade tumor that rarely occurs in the urinary bladder. There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports. CASE SUMMARY A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria. Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder. The mass had an abundant blood supply. For further diagnosis, transurethral cystoscopic biopsy and bone marrow biopsy was performed, and the patient was finally diagnosed with primary MALT lymphoma of the bladder. R-CHOP chemotherapy was carried out. After three cycles of chemotherapy, the mass disappeared and the bladder wall thickness was only 4 mm, which indicated excellent therapeutic response to the chemotherapy. To date, the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles. CONCLUSION Primary MALT lymphoma of the bladder is rare, and there are certain characteristics in the ultrasonographic findings. Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.
Published: 2021

50. Tall cell carcinoma with reversed polarity: case report with gene sequencing and literature review

Author: Qingyu Guan, Yufan Wei, Xiru Li, Xin Song, Ningning Min, Xia Tian, Mei Liu, and Liming Ding
Subjects: Tall cell, business.industry, Carcinoma, medicine, Reversed polarity, Case Report, Surgery, medicine.disease, business, Molecular biology, DNA sequencing
Abstract: Tall cell carcinoma with reversed polarity (TCCRP) is an extremely rare type of invasive breast cancer with only 17 literatures and 75 cases reported. Knowledge on TCCRP is still scanty. The present study reported 2 cases of TCCRP, analyzed their clinicopathological characteristics, and used whole exome sequencing to perform genetic testing. Both two cases were proved to have typical clinicopathological manifestations (solid and papillary architectures lined by tall columnar cells with nuclei displaying “reverse polarization”) and hotspot mutations (IDH2 and PIK3CA mutations) of TCCRP. Furthermore, positive expression of TTF-1 was found in a small number of tumor cells nuclei and normal ductal epithelial cells, while the negative rate of TTF-1 in previous case reports was 100%. Attention should be paid in core needle biopsy to avoid misdiagnosis. In addition, this article also reviewed all previous cases and demonstrated that the positive expression of calretinin might have an indicative significance for TCCRP, which could be used as one of the auxiliary diagnosis tools. The diagnosis of TCCRP requires comprehensive analysis of clinical pathology and genetic testing results. There is no clear treatment standard for TCCRP currently, further research should be reported to characterize and deeply investigate the diagnosis and treatment criteria of TCCRP.
Published: 2021
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