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Multiorgan locked-state model of chronic diseases and systems pharmacology opportunities

DRUG DISCOVERY TODAY (2024)

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Article Multidisciplinary Sciences

Predicting cascading extinctions and efficient restoration strategies in plant-pollinator networks via generalized positive feedback loops

Fatemeh Sadat Fatemi Nasrollahi et al.

Summary: The extinction of a species in a plant-pollinator mutualistic community can lead to major biodiversity loss. It is challenging to predict the severity of the cascading effects due to the complex network of interactions. In this study, models of plant and pollinator communities are analyzed, and positive feedback loops are identified as crucial for predicting catastrophic damage to the community. Mitigation measures for preventing and restoring community damage are suggested, with the analysis indicating that positive feedback loops are effective strategies.

SCIENTIFIC REPORTS (2023)

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Review Biochemistry & Molecular Biology

Accelerating the understanding of cancer biology through the lens of genomics

Dongfang Wang et al.

Summary: The core mission of cancer genomics is to comprehensively understand the molecular basis of cancer-driving events and provide personalized therapeutic strategies. Initially focused on cancer cells, this field has identified many drivers for major cancer types. With the recognition of cancer immune evasion as a crucial hallmark, the paradigm has shifted towards studying the holistic tumor ecosystem and elucidating the functional states of its cellular components. This review highlights the milestones of cancer genomics, describes the evolving path of the field, and discusses future directions in advancing our understanding of the tumor ecosystem and developing improved therapeutic strategies.

CELL (2023)

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Article Chemistry, Medicinal

TransOrGAN: An Artificial Intelligence Mapping of Rat Transcriptomic Profiles between Organs, Ages, and Sexes

Ting Li et al.

Summary: Animal studies are crucial for drug evaluation to ensure safety. We have proposed a novel framework called TransOrGAN that uses a generative adversarial network to map gene expression profiles across different organ systems, sexes, and ages in rodents. Our proof-of-concept study demonstrates that TransOrGAN can accurately infer transcriptomic profiles between organs, sexes, and ages, providing an opportunity to reduce animal usage and assess overall toxicity.

CHEMICAL RESEARCH IN TOXICOLOGY (2023)

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Editorial Material Multidisciplinary Sciences

Network-based cancer precision prevention with artificial intelligence and multi-omics

Peng Zhang et al.

SCIENCE BULLETIN (2023)

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Article Pharmacology & Pharmacy

A decision support system based on artificial intelligence and systems biology for the simulation of pancreatic cancer patient status

Valentin Junet et al.

Summary: This study aimed to predict the next visit of patients with pancreatic cancer using clinical data, providing decision support for clinicians. Models based on regression trees were generated to predict the evolution of hematological variables at the next visit. The inclusion of molecular variables from in silico simulations provided a molecular background for the observed variations in the selected outcome variables.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2023)

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Article Biochemical Research Methods

GAN-based data augmentation for transcriptomics: survey and comparative assessment

Alice Lacan et al.

Summary: This article analyzes the application of GAN-based data augmentation strategies in cancer phenotype classification. The results show a significant improvement in binary and multiclass classification performance through data augmentation. Without augmentation, the accuracy of classifiers trained on only 50 RNA-seq samples is 94% and 70% for binary and tissue classification respectively, while adding 1000 augmented samples increases the accuracy to 98% and 94%. The strength and training cost of the generative models positively correlate with the augmentation performance and generated data quality. Multiple performance indicators are required to assess the quality of the generated data correctly.

BIOINFORMATICS (2023)

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Review Pharmacology & Pharmacy

Manifold medicine: A schema that expands treatment dimensionality

Choong Yong Ung et al.

Summary: The concept of "Manifold Medicine" introduces a new approach to drug discovery by describing disease states as multidimensional vectors on body-wide axes, offering a strategy for designing manifold drug cocktails and translating knowledge gained from nextgeneration technologies into individualized clinical practice.

DRUG DISCOVERY TODAY (2022)

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Article Biochemistry & Molecular Biology

De novo individualized disease modules reveal the synthetic penetrance of genes and inform personalized treatment regimens

Taylor M. Weiskittel et al.

Summary: Despite the limited understanding of individual disease etiology and therapeutics, a novel computational pipeline has been proposed to collect potent disease gene cooperative pathways for individualized disease etiology and therapies. The importance of mutated genes in specific patients and the synthetic penetrance of these genes across patients can be elucidated through individualized disease modules. This study reveals the fluctuation of importance for notorious cancer drivers in breast cancers and the high disease module importance of rarely mutated genes in specific individuals. Furthermore, customized singular and combinatorial target therapies can be devised through individualized module disruption, emphasizing the need for precision therapeutics pipelines. This analysis demonstrates the power of individualized disease modules for precision medicine, offering deep novel insights on the activity of diseased genes in individuals.

GENOME RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Ligand-receptor promiscuity enables cellular addressing

Christina J. Su et al.

Summary: The study reveals that promiscuously interacting ligand-receptor systems allow a small number of ligands to address a larger number of cell types through combinatorial interactions, which is different from the traditional one-to-one signaling architecture. This combinatorial addressing capability is robust and can be optimized by adjusting the biochemical parameter relationships.

CELL SYSTEMS (2022)

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Article Multidisciplinary Sciences

Identification of kidney injury-released circulating osteopontin as causal agent of respiratory failure

Fatima Zohra Khamissi et al.

Summary: This study identifies circulating osteopontin (OPN) released from kidney tubule cells as a novel mediator in acute kidney injury (AKI)-induced acute lung injury (ALI). OPN triggers lung endothelial leakage, inflammation, and respiratory failure. The study also demonstrates the elevated levels of OPN in AKI patients and its correlation with kidney injury.

SCIENCE ADVANCES (2022)

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Article Engineering, Biomedical

A multi-organ chip with matured tissue niches linked by vascular flow

Kacey Ronaldson-Bouchard et al.

Summary: This study reports the development and application of a tissue-chip system where matured human heart, liver, bone, and skin tissue niches are interconnected by recirculating vascular flow, allowing for the replication of interdependent organ functions and potentially enhancing clinical applicability.

NATURE BIOMEDICAL ENGINEERING (2022)

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Review Mathematical & Computational Biology

Computational systems biology in disease modeling and control, review and perspectives

Rongting Yue et al.

Summary: Omics-based approaches are increasingly influential in identifying disease mechanisms and drug responses. Integrating omics data from different layers and combining known drug reactions can predict potential molecular interactions and improve therapeutic performance. This review introduces the applications and analyses of gene, protein, and drug molecule interactions and discusses the challenges in clinical use.

NPJ SYSTEMS BIOLOGY AND APPLICATIONS (2022)

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Article Biochemistry & Molecular Biology

Gene utility recapitulates chromosomal aberrancies in advanced stage neuroblastoma

Choong Y. Ung et al.

Summary: This article introduces the Gene Utility Model (GUM) to understand the impact of differentially utilized genes on neuroblastoma karyotype evolution. Through computational modeling and comparative analysis, genes with differential utilities in neuroblastoma were identified and mapped to a utility karyotype that recapitulates chromosomal abnormalities and provides clues to predisposition sites. This study offers new insights into the etiology of neuroblastoma and facilitates the identification of novel therapeutic targets.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2022)

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Article Multidisciplinary Sciences

Biologically informed deep neural network for prostate cancer discovery

Haitham A. Elmarakeby et al.

Summary: The development of a biologically informed deep learning model P-NET enables stratification of prostate cancer patients by treatment-resistance state and evaluation of molecular drivers of treatment resistance for therapeutic targeting with complete model interpretability. This approach shows superior performance in cancer state prediction using molecular data compared to other modeling approaches.

NATURE (2021)

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Review Biotechnology & Applied Microbiology

Multiorgan-on-a-Chip: A Systemic Approach To Model and Decipher Inter-Organ Communication

Nathalie Picollet-D'hahan et al.

Summary: Multiorgan-on-a-chip platforms have the potential to redefine human health research by providing comprehensive and personalized models for understanding and treating multisystem diseases. These models offer unique information that is not accessible with single-organ-on-a-chip models, but there are still challenges to overcome in realizing and adopting these platforms worldwide.

TRENDS IN BIOTECHNOLOGY (2021)

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Review Oncology

Emerging roles of exosomal miRNAs in diabetes mellitus

Xiaoyun He et al.

Summary: Exosomes are small vesicles secreted by cells and can carry various cargo including RNA, DNA, proteins, and metabolites. Studies have shown that exosomal microRNAs play a crucial role in the progression of diseases such as diabetes mellitus, affecting processes like pancreatic beta-cell injury and insulin resistance. Understanding the mechanisms of exosomal miRNAs in diabetes mellitus can provide valuable insights for identifying diagnostic biomarkers and drug targets.

CLINICAL AND TRANSLATIONAL MEDICINE (2021)

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Article Immunology

Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis

Izabela Rumienczyk et al.

Summary: Using RNA sequencing in a sepsis murine model, significant transcriptional changes were found in multiple organs during the early phase of sepsis, with alterations in immune system and lipid metabolism. These findings may lead to new research directions and treatment strategies for sepsis-induced MODS.

JOURNAL OF INFLAMMATION RESEARCH (2021)

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Article Medicine, Research & Experimental

Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs

Francesca Solagna et al.

Summary: This study investigated the mechanism of skeletal muscle wasting in CKD and found that the soluble pro-cachectic factor activin A is expressed in specific kidney cell populations, proposing a vicious signaling cycle between kidney and muscle. Blocking activin A signaling pharmacologically prevented muscle wasting in experimental CKD mouse models.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Review Genetics & Heredity

Deciphering cell-cell interactions and communication from gene expression

Erick Armingol et al.

Summary: Intercellular interactions and communication can be inferred from RNA sequencing data, such as ligand-receptor pairs, which has led to new insights and methodologies for studying cell-cell interactions.

NATURE REVIEWS GENETICS (2021)

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Article Multidisciplinary Sciences

Realistic in silico generation and augmentation of single-cell RNA-seq data using generative adversarial networks

Mohamed Marouf et al.

NATURE COMMUNICATIONS (2020)

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Article Medicine, Research & Experimental

Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts

Subrata Chowdhury et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Endocrinology & Metabolism

The Interplay Between Bone and Glucose Metabolism

Cristiana Cipriani et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

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Article Multidisciplinary Sciences

Ageing hallmarks exhibit organ-specific temporal signatures

Nicholas Schaum et al.

NATURE (2020)

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Article Ecology

Positive feedback loop between earthworms, humus form and soil pH reinforces earthworm abundance in European forests

Ellen Desie et al.

FUNCTIONAL ECOLOGY (2020)

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Article Medicine, General & Internal

Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes

Nicholas Bowker et al.

EBIOMEDICINE (2020)

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Article Rheumatology

Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials

Mark C. Genovese et al.

ARTHRITIS RESEARCH & THERAPY (2020)

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Article Biochemical Research Methods

Network-Based Combinatorial CRISPR-Cas9 Screens Identify Synergistic Modules in Human Cells

Yucheng Guo et al.

ACS SYNTHETIC BIOLOGY (2019)

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Article Cell Biology

Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Peng Zhang et al.

CELL REPORTS (2019)

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Review Pharmacology & Pharmacy

Targeting Super-Enhancers as a Therapeutic Strategy for Cancer Treatment

Yi He et al.

FRONTIERS IN PHARMACOLOGY (2019)

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Review Oncology

Super-enhancers: critical roles and therapeutic targets in hematologic malignancies

Yunlu Jia et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2019)

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Review Biochemistry & Molecular Biology

Inter-organ communication: a gatekeeper for metabolic health

Judit Castillo-Armengol et al.

EMBO REPORTS (2019)

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Review Endocrinology & Metabolism

Circadian clocks and insulin resistance

Dirk Jan Stenvers et al.

NATURE REVIEWS ENDOCRINOLOGY (2019)

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Article Cell Biology

A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism

Marcus M. Seldin et al.

CELL METABOLISM (2018)

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Article Medicine, Research & Experimental

An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers

Melanie Mahe et al.

EMBO MOLECULAR MEDICINE (2018)

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Article Endocrinology & Metabolism

Circadian regulation of glucose, lipid, and energy metabolism in humans

Eleonora Poggiogalle et al.

METABOLISM-CLINICAL AND EXPERIMENTAL (2018)

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Review Genetics & Heredity

Integrative omics for health and disease

Konrad J. Karczewski et al.

NATURE REVIEWS GENETICS (2018)

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Review Physiology

INTERORGAN METABOLIC CROSSTALK IN HUMAN INSULIN RESISTANCE

Sofiya Gancheva et al.

PHYSIOLOGICAL REVIEWS (2018)

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Article Engineering, Biomedical

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

Carlota Oleaga et al.

BIOMATERIALS (2018)

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Article Oncology

Addressing heterogeneity in the design of phase II clinical trials in geriatric oncology

Bastien Cabarrou et al.

EUROPEAN JOURNAL OF CANCER (2018)

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Review Neurosciences

Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System

Arnaud Bessac et al.

FRONTIERS IN NEUROSCIENCE (2018)

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Article Cell Biology

Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF

Daniela F. Quail et al.

NATURE CELL BIOLOGY (2017)

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Review Genetics & Heredity

Comparative transcriptomics in human and mouse

Alessandra Breschi et al.

NATURE REVIEWS GENETICS (2017)

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Article Multidisciplinary Sciences

Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models

Yuichiro Mita et al.

NATURE COMMUNICATIONS (2017)

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Article Multidisciplinary Sciences

Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks

Mehrab Ghanat Bari et al.

SCIENTIFIC REPORTS (2017)

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Article Genetics & Heredity

Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States

Le Shu et al.

PLOS GENETICS (2017)

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Review Endocrinology & Metabolism

Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral Neuropathy

April Ann Cox et al.

FRONTIERS IN ENDOCRINOLOGY (2017)

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Article Oncology

Multiscale Modeling of Inflammation-Induced Tumorigenesis Reveals Competing Oncogenic and Oncoprotective Roles for Inflammation

Yucheng Guo et al.

CANCER RESEARCH (2017)

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Article Pharmacology & Pharmacy

Muscle as a paracrine and endocrine organ

Jimena Giudice et al.

CURRENT OPINION IN PHARMACOLOGY (2017)

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Article Immunology

Social network architecture of human immune cells unveiled by quantitative proteomics

Jan C. Rieckmann et al.

NATURE IMMUNOLOGY (2017)

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Review Oncology

Pre-metastatic niches: organ-specific homes for metastases

Hector Peinado et al.

NATURE REVIEWS CANCER (2017)

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Article Nanoscience & Nanotechnology

Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis

Zhiyun Xu et al.

ACS APPLIED MATERIALS & INTERFACES (2016)

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Review Biochemistry & Molecular Biology

Bone and Muscle Endocrine Functions: Unexpected Paradigms of Inter-organ Communication

Gerard Karsenty et al.

CELL (2016)

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Article Genetics & Heredity

Functional characterization of somatic mutations in cancer using network-based inference of protein activity

Mariano J. Alvarez et al.

NATURE GENETICS (2016)

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Article Multidisciplinary Sciences

A Comprehensive Inter-Tissue Crosstalk Analysis Underlying Progression and Control of Obesity and Diabetes

Pawan Samdani et al.

SCIENTIFIC REPORTS (2015)

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Editorial Material Biochemistry & Molecular Biology

Living too long

Guy C. Brown

EMBO REPORTS (2015)

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Article Biochemistry & Molecular Biology

CellNet: Network Biology Applied to Stem Cell Engineering

Patrick Cahan et al.

CELL (2014)

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Article Biochemistry & Molecular Biology

Embracing patient heterogeneity

NATURE MEDICINE (2014)

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Article Biotechnology & Applied Microbiology

A kinetic model of the evolution of a protein interaction network

Piotr H. Pawlowski et al.

BMC GENOMICS (2013)

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Article Endocrinology & Metabolism

Bimodal Effect on Pancreatic β-Cells of Secretory Products From Normal or Insulin-Resistant Human Skeletal Muscle

Karim Bouzakri et al.

DIABETES (2011)

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Article Biochemistry & Molecular Biology

Making Cellular Memories

Devin R. Burrill et al.

CELL (2010)

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Article Multidisciplinary Sciences

Reconstituting Organ-Level Lung Functions on a Chip

Dongeun Huh et al.

SCIENCE (2010)

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Article Biochemistry & Molecular Biology

Network-based global inference of human disease genes

Xuebing Wu et al.

MOLECULAR SYSTEMS BIOLOGY (2008)

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Article Medicine, General & Internal

Chronic diseases 1 - The burden and costs of chronic diseases in low-income and middle-income countries

Dele O. Abegunde et al.

LANCET (2007)

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Review Oncology

Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms

EE Calle et al.

NATURE REVIEWS CANCER (2004)

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Article Multidisciplinary Sciences

The burden of chronic disease

CGN Mascie-Taylor et al.

SCIENCE (2003)

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Article Multidisciplinary Sciences

A positive-feedback-based bistable 'memory module' that governs a cell fate decision

W Xiong et al.

NATURE (2003)

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Article Multidisciplinary Sciences

Large-scale analysis of the human and mouse transcriptomes

AI Su et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2002)

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