283 results match your criteria Annual review of pathology[Journal]


Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories.

Annu Rev Pathol 2020 Apr 14. Epub 2020 Apr 14.

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 USA; email:

It was first demonstrated in the late 19th century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the 20th century, when it became apparent that only a small proportion of infected individuals die from primary infections with almost any given microbe. Read More

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http://dx.doi.org/10.1146/annurev-pathol-031920-101429DOI Listing

Contributions of Eosinophils to Human Health and Disease.

Annu Rev Pathol 2020 01;15:179-209

Department of Medicine, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA; email:

The human eosinophil has long been thought to favorably influence innate mucosal immunity but at times has also been incriminated in disease pathophysiology. Research into eosinophil biology has uncovered a number of interesting contributions by eosinophils to health and disease. However, it appears that not all eosinophils from all species are created equal. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032756DOI Listing
January 2020

Enabling Precision Oncology Through Precision Diagnostics.

Annu Rev Pathol 2020 01;15:97-121

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Genomic testing enables clinical management to be tailored to individual cancer patients based on the molecular alterations present within cancer cells. Genomic sequencing results can be applied to detect and classify cancer, predict prognosis, and target therapies. Next-generation sequencing has revolutionized the field of cancer genomics by enabling rapid and cost-effective sequencing of large portions of the genome. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012735DOI Listing
January 2020

Genomic and Epigenomic Alterations in Chronic Lymphocytic Leukemia.

Annu Rev Pathol 2020 01;15:149-177

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; email:

Chronic lymphocytic leukemia is a common disease in Western countries and has heterogeneous clinical behavior. The relevance of the genetic basis of the disease has come to the forefront recently, with genome-wide studies that have provided a comprehensive view of structural variants, somatic mutations, and different layers of epigenetic changes. The mutational landscape is characterized by relatively common copy number alterations, a few mutated genes occurring in 10-15% of cases, and a large number of genes mutated in a small number of cases. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032810DOI Listing
January 2020

Unraveling Disease Pathophysiology with Mathematical Modeling.

Annu Rev Pathol 2020 01;15:371-394

Center for Systems Biology and Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; email:

Modeling has enabled fundamental advances in our understanding of the mechanisms of health and disease for centuries, since at least the time of William Harvey almost 500 years ago. Recent technological advances in molecular methods, computation, and imaging generate optimism that mathematical modeling will enable the biomedical research community to accelerate its efforts in unraveling the molecular, cellular, tissue-, and organ-level processes that maintain health, predispose to disease, and determine response to treatment. In this review, we discuss some of the roles of mathematical modeling in the study of human physiology and pathophysiology and some challenges and opportunities in general and in two specific areas: in vivo modeling of pulmonary function and in vitro modeling of blood cell populations. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032557DOI Listing
January 2020

Our Conflict with Transposable Elements and Its Implications for Human Disease.

Authors:
Kathleen H Burns

Annu Rev Pathol 2020 01;15:51-70

Department of Pathology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Our genome is a historic record of successive invasions of mobile genetic elements. Like other eukaryotes, we have evolved mechanisms to limit their propagation and minimize the functional impact of new insertions. Although these mechanisms are vitally important, they are imperfect, and a handful of retroelement families remain active in modern humans. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032633DOI Listing
January 2020

The Pathogenesis of Nodding Syndrome.

Annu Rev Pathol 2020 01;15:395-417

Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA; email:

Nodding syndrome is a rare, enigmatic form of pediatric epilepsy that has occurred in an epidemic fashion beginning in the early 2000s in geographically distinct regions of Africa. Despite extensive investigation, the etiology of nodding syndrome remains unclear, although much progress has been made in understanding the pathogenesis of the disease, as well as in treatment and prevention. Nodding syndrome is recognized as a defined disease entity, but it is likely one manifestation along a continuum of -associated neurological complications. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032748DOI Listing
January 2020

SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models.

Annu Rev Pathol 2020 01;15:467-492

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada; email:

The SWI/SNF (mating type ch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986318PMC
January 2020

Cardiovascular Disease, Aging, and Clonal Hematopoiesis.

Annu Rev Pathol 2020 01 5;15:419-438. Epub 2019 Nov 5.

Hematovascular Biology Center and the Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA; email:

Traditional risk factors are incompletely predictive of cardiovascular disease development, a leading cause of death in the elderly. Recent epidemiological studies have shown that human aging is associated with an increased frequency of somatic mutations in the hematopoietic system, which provide a competitive advantage to a mutant cell, thus allowing for its clonal expansion, a phenomenon known as clonal hematopoiesis. Unexpectedly, these mutations have been associated with a higher incidence of cardiovascular disease, suggesting a previously unrecognized connection between somatic mutations in hematopoietic cells and cardiovascular disease. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104598PMC
January 2020

DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation.

Annu Rev Pathol 2020 01 1;15:493-518. Epub 2019 Nov 1.

Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; email:

Recognizing the importance of leukocyte trafficking in inflammation led to some therapeutic breakthroughs. However, many inflammatory pathologies remain without specific therapy. This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile (non-microbial) molecules, comprising damage-associated molecular patterns (DAMPs). Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032847DOI Listing
January 2020
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Legionnaires' Disease: State of the Art Knowledge of Pathogenesis Mechanisms of .

Annu Rev Pathol 2020 01 28;15:439-466. Epub 2019 Oct 28.

Institut Pasteur, Biologie des Bactéries Intracellulaires, CNRS UMR 3525, 75015 Paris, France; email:

species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of in 1977, four decades of research on biology and Legionnaires' disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032742DOI Listing
January 2020
2 Reads

New Insights into Malaria Pathogenesis.

Annu Rev Pathol 2020 01 24;15:315-343. Epub 2019 Oct 24.

Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, United Kingdom; email:

Malaria remains a major public health threat in tropical and subtropical regions across the world. Even though less than 1% of malaria infections are fatal, this leads to about 430,000 deaths per year, predominantly in young children in sub-Saharan Africa. Therefore, it is imperative to understand why a subset of infected individuals develop severe syndromes and some of them die and what differentiates these cases from the majority that recovers. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032640DOI Listing
January 2020
4 Reads

Molecular Pathogenesis of Membranous Nephropathy.

Annu Rev Pathol 2020 01 17;15:287-313. Epub 2019 Oct 17.

Rare and Common Kidney Diseases: From Molecular Mechanisms to Personalized Medicine Unit, INSERM UMRS 1155, Sorbonne Université, 75020 Paris, France; email:

Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLAR), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043811DOI Listing
January 2020
4 Reads

Microbial Contribution to the Human Metabolome: Implications for Health and Disease.

Annu Rev Pathol 2020 01 17;15:345-369. Epub 2019 Oct 17.

Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA; email:

The human gastrointestinal tract is home to an incredibly dense population of microbes. These microbes employ unique strategies to capture energy in this largely anaerobic environment. In the process of breaking down dietary- and host-derived substrates, the gut microbiota produce a broad range of metabolic products that accumulate to high levels in the gut. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathol-020
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http://dx.doi.org/10.1146/annurev-pathol-020117-043559DOI Listing
January 2020
25 Reads

Autophagy Defects in Skeletal Myopathies.

Authors:
Marta Margeta

Annu Rev Pathol 2020 01 8;15:261-285. Epub 2019 Oct 8.

Department of Pathology, University of California, San Francisco, California 94143, USA; email:

Autophagy is an evolutionarily conserved catabolic process that targets different types of cytoplasmic cargo (such as bulk cytoplasm, damaged cellular organelles, and misfolded protein aggregates) for lysosomal degradation. Autophagy is activated in response to biological stress and also plays a critical role in the maintenance of normal cellular homeostasis; the latter function is particularly important for the integrity of postmitotic, metabolically active tissues, such as skeletal muscle. Through impairment of muscle homeostasis, autophagy dysfunction contributes to the pathogenesis of many different skeletal myopathies; the observed autophagy defects differ from disease to disease but have been shown to involve all steps of the autophagic cascade (from induction to lysosomal cargo degradation) and to impair both bulk and selective autophagy. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032618DOI Listing
January 2020

Mitochondrial Dynamics and Its Involvement in Disease.

Authors:
David C Chan

Annu Rev Pathol 2020 01 4;15:235-259. Epub 2019 Oct 4.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA; email:

The dynamic properties of mitochondria-including their fusion, fission, and degradation-are critical for their optimal function in energy generation. The interplay of fusion and fission confers widespread benefits on mitochondria, including efficient transport, increased homogenization of the mitochondrial population, and efficient oxidative phosphorylation. These benefits arise through control of morphology, content exchange, equitable inheritance of mitochondria, maintenance of high-quality mitochondrial DNA, and segregation of damaged mitochondria for degradation. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032711DOI Listing
January 2020

Human Organoids: Tools for Understanding Biology and Treating Diseases.

Annu Rev Pathol 2020 01 24;15:211-234. Epub 2019 Sep 24.

Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands; email:

Organoids are in vitro-cultured three-dimensional structures that recapitulate key aspects of in vivo organs. They can be established from pluripotent stem cells and from adult stem cells, the latter being the subject of this review. Organoids derived from adult stem cells exploit the tissue regeneration process that is driven by these cells, and they can be established directly from the healthy or diseased epithelium of many organs. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032611DOI Listing
January 2020

Diversity, Mechanisms, and Significance of Macrophage Plasticity.

Annu Rev Pathol 2020 01 17;15:123-147. Epub 2019 Sep 17.

Humanitas Clinical and Research Center, 20089 Milan, Italy; email:

Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow-derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176483PMC
January 2020

The Origin and Pathogenesis of Endometriosis.

Annu Rev Pathol 2020 01 3;15:71-95. Epub 2019 Sep 3.

Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA; email:

Recent molecular genetic findings on endometriosis and normal endometrium suggest a modified model in which circulating epithelial progenitor or stem cells intended to regenerate uterine endometrium after menstruation may become overreactive and trapped outside the uterus. These trapped epithelium-committed progenitor cells form nascent glands through clonal expansion and recruit polyclonal stromal cells, leading to the establishment of deep infiltrating endometriosis. Once formed, the ectopic tissue becomes subject to immune surveillance, resulting in chronic inflammation. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032654DOI Listing
January 2020
2 Reads

Liver Progenitors and Adult Cell Plasticity in Hepatic Injury and Repair: Knowns and Unknowns.

Annu Rev Pathol 2020 01 9;15:23-50. Epub 2019 Aug 9.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA; email:

The liver is a complex organ performing numerous vital physiological functions. For that reason, it possesses immense regenerative potential. The capacity for repair is largely attributable to the ability of its differentiated epithelial cells, hepatocytes and biliary epithelial cells, to proliferate after injury. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212705PMC
January 2020
3 Reads

Development of the Intrahepatic and Extrahepatic Biliary Tract: A Framework for Understanding Congenital Diseases.

Annu Rev Pathol 2020 01 12;15:1-22. Epub 2019 Jul 12.

de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium; email:

The involvement of the biliary tract in the pathophysiology of liver diseases and the increased attention paid to bile ducts in the bioconstruction of liver tissue for regenerative therapy have fueled intense research into the fundamental mechanisms of biliary development. Here, I review the molecular, cellular and tissular mechanisms driving differentiation and morphogenesis of the intrahepatic and extrahepatic bile ducts. This review focuses on the dynamics of the transcriptional and signaling modules that promote biliary development in human and mouse liver and discusses studies in which the use of zebrafish uncovered unexplored processes in mammalian biliary development. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013013DOI Listing
January 2020

Malformations of Cerebral Cortex Development: Molecules and Mechanisms.

Annu Rev Pathol 2019 01;14:293-318

Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA; email: ,

Malformations of cortical development encompass heterogeneous groups of structural brain anomalies associated with complex neurodevelopmental disorders and diverse genetic and nongenetic etiologies. Recent progress in understanding the genetic basis of brain malformations has been driven by extraordinary advances in DNA sequencing technologies. For example, somatic mosaic mutations that activate mammalian target of rapamycin signaling in cortical progenitor cells during development are now recognized as the cause of hemimegalencephaly and some types of focal cortical dysplasia. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938687PMC
January 2019
2 Reads

Systems-Wide Approaches in Induced Pluripotent Stem Cell Models.

Annu Rev Pathol 2019 01 31;14:395-419. Epub 2018 Oct 31.

Stanford Cardiovascular Institute, and Department of Medicine, Division of Cardiology, Stanford University, Stanford, California 94305, USA; email:

Human induced pluripotent stem cells (iPSCs) provide a renewable supply of patient-specific and tissue-specific cells for cellular and molecular studies of disease mechanisms. Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. In the past 2 years, large panels of iPSC lines have been derived from hundreds of genetically heterogeneous individuals, further enabling genome-wide mapping to identify coexpression networks and elucidate gene regulatory networks. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450651PMC
January 2019
4 Reads

Molecular Pathogenesis of the Tauopathies.

Annu Rev Pathol 2019 01 24;14:239-261. Epub 2018 Oct 24.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St. Lucia Campus, Brisbane, Queensland 4072, Australia; email:

The tauopathies constitute a group of diseases that have Tau inclusions in neurons or glia as their common denominator. In this review, we describe the biochemical and histological differences in Tau pathology that are characteristic of the spectrum of frontotemporal lobar degeneration as primary tauopathies and of Alzheimer's disease as a secondary tauopathy, as well as the commonalities and differences between the familial and sporadic forms. Furthermore, we discuss selected advances in transgenic animal models in delineating the different pathomechanisms of Tau. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012936DOI Listing
January 2019
1 Read

Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection.

Annu Rev Pathol 2019 01 24;14:319-338. Epub 2018 Oct 24.

Department of Laboratory Medicine, University of California, San Francisco, California 94107, USA; email:

Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345613PMC
January 2019
40 Reads

Modeling Disease with Human Inducible Pluripotent Stem Cells.

Annu Rev Pathol 2019 01 24;14:449-468. Epub 2018 Oct 24.

Wellcome and MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; email:

Understanding the physiopathology of disease remains an essential step in developing novel therapeutics. Although animal models have certainly contributed to advancing this enterprise, their limitation in modeling all the aspects of complex human disorders is one of the major challenges faced by the biomedical research field. Human induced pluripotent stem cells (hiPSCs) derived from patients represent a great opportunity to overcome this deficiency because these cells cover the genetic diversity needed to fully model human diseases. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043634DOI Listing
January 2019
1 Read

Pathology and Pathogenesis of Chagas Heart Disease.

Annu Rev Pathol 2019 01 24;14:421-447. Epub 2018 Oct 24.

Department of Pathology and Laboratory Medicine and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA; email: , ,

Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathol-020
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http://dx.doi.org/10.1146/annurev-pathol-020117-043711DOI Listing
January 2019
29 Reads

RNA Binding Proteins and the Pathogenesis of Frontotemporal Lobar Degeneration.

Annu Rev Pathol 2019 01 24;14:469-495. Epub 2018 Oct 24.

Department of Pathology, University of California, San Francisco, California 94143, USA; email:

Frontotemporal dementia is a group of early onset dementia syndromes linked to underlying frontotemporal lobar degeneration (FTLD) pathology that can be classified based on the formation of abnormal protein aggregates involving tau and two RNA binding proteins, TDP-43 and FUS. Although elucidation of the mechanisms leading to FTLD pathology is in progress, recent advances in genetics and neuropathology indicate that a majority of FTLD cases with proteinopathy involving RNA binding proteins show highly congruent genotype-phenotype correlations. Specifically, recent studies have uncovered the unique properties of the low-complexity domains in RNA binding proteins that can facilitate liquid-liquid phase separation in the formation of membraneless organelles. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731550PMC
January 2019
6 Reads

Cellular and Molecular Mechanisms of Prion Disease.

Annu Rev Pathol 2019 01 24;14:497-516. Epub 2018 Oct 24.

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Prion diseases are rapidly progressive, incurable neurodegenerative disorders caused by misfolded, aggregated proteins known as prions, which are uniquely infectious. Remarkably, these infectious proteins have been responsible for widespread disease epidemics, including kuru in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids, the latter of which has spread across North America and recently appeared in Norway and Finland. The hallmark histopathological features include widespread spongiform encephalopathy, neuronal loss, gliosis, and deposits of variably sized aggregated prion protein, ranging from small, soluble oligomers to long, thin, unbranched fibrils, depending on the disease. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013109DOI Listing
January 2019
18 Reads

Molecular Genetics of Endometrial Carcinoma.

Annu Rev Pathol 2019 01 17;14:339-367. Epub 2018 Oct 17.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York 10065, USA; email:

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3-10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043609DOI Listing
January 2019
4 Reads

Pathophysiology of Sickle Cell Disease.

Annu Rev Pathol 2019 01 17;14:263-292. Epub 2018 Oct 17.

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to end-organ ischemia-reperfusion injury and infarction. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053558PMC
January 2019
8 Reads

Opportunities for microRNAs in the Crowded Field of Cardiovascular Biomarkers.

Annu Rev Pathol 2019 01 17;14:211-238. Epub 2018 Oct 17.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Cardiovascular diseases exist across all developed countries. Biomarkers that can predict or diagnose diseases early in their pathogeneses can reduce their morbidity and mortality in afflicted individuals. microRNAs are small regulatory RNAs that modulate translation and have been identified as potential fluid-based biomarkers across numerous maladies. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442682PMC
January 2019
5 Reads
18.750 Impact Factor

Type I Interferons in Autoimmune Disease.

Annu Rev Pathol 2019 01 17;14:369-393. Epub 2018 Oct 17.

Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, New York 10021, USA; email:

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043952DOI Listing
January 2019
10 Reads

Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases.

Annu Rev Pathol 2019 01 19;14:153-184. Epub 2018 Sep 19.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; email:

The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013003DOI Listing
January 2019
16 Reads
18.750 Impact Factor

Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications.

Annu Rev Pathol 2019 01 5;14:185-210. Epub 2018 Sep 5.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

Pregnancy stimulates an elaborate assortment of dynamic changes, allowing intimate approximation of genetically discordant maternal and fetal tissues. Although the cellular and molecular details about how this works remain largely undefined, important clues arise from evaluating how a prior pregnancy influences the outcome of a future pregnancy. The risk of complications is consistently increased when complications occurred in a prior pregnancy. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566855PMC
January 2019
3 Reads

Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection.

Annu Rev Pathol 2019 01 27;14:127-152. Epub 2018 Aug 27.

The University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0609, USA; email: , , ,

Obligately intracytosolic rickettsiae that cycle between arthropod and vertebrate hosts cause human diseases with a spectrum of severity, primarily by targeting microvascular endothelial cells, resulting in endothelial dysfunction. Endothelial cells and mononuclear phagocytes have important roles in the intracellular killing of rickettsiae upon activation by the effector molecules of innate and adaptive immunity. In overwhelming infection, immunosuppressive effects contribute to the severity of illness. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505701PMC
January 2019
2 Reads

Pathological Issues in Dystrophinopathy in the Age of Genetic Therapies.

Annu Rev Pathol 2019 01 27;14:105-126. Epub 2018 Aug 27.

Department of Pathology and Laboratory Medicine, and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA; email: , ,

Dystrophinopathy is a class of genetic skeletal muscle disease characterized by myofiber degeneration and regeneration due to insufficient levels or functioning of dystrophin. Pathological evaluation for dystrophinopathy includes the identification of dystrophic skeletal muscle pathology and the immunohistochemical evaluation of dystrophin epitopes, but biopsies have become rare in recent years. However, the evaluation of dystrophin expression in the research setting has become critically important due to recent advances in genetic therapies, including exon skipping and gene therapy. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012945DOI Listing
January 2019
6 Reads

Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology.

Annu Rev Pathol 2019 01 20;14:83-103. Epub 2018 Aug 20.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02215, USA; email: , ,

Evidence indicates that diet, nutrition, lifestyle, the environment, the microbiome, and other exogenous factors have pathogenic roles and also influence the genome, epigenome, transcriptome, proteome, and metabolome of tumor and nonneoplastic cells, including immune cells. With the need for big-data research, pathology must transform to integrate data science fields, including epidemiology, biostatistics, and bioinformatics. The research framework of molecular pathological epidemiology (MPE) demonstrates the strengths of such an interdisciplinary integration, having been used to study breast, lung, prostate, and colorectal cancers. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345592PMC
January 2019
4 Reads

Epstein-Barr Virus and Cancer.

Authors:
Paul J Farrell

Annu Rev Pathol 2019 01 20;14:29-53. Epub 2018 Aug 20.

Section of Virology, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom; email:

Epstein-Barr virus (EBV) contributes to about 1.5% of all cases of human cancer worldwide, and viral genes are expressed in the malignant cells. EBV also very efficiently causes the proliferation of infected human B lymphocytes. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013023DOI Listing
January 2019
6 Reads

Exposure to Ultraviolet Radiation in the Modulation of Human Diseases.

Annu Rev Pathol 2019 01 20;14:55-81. Epub 2018 Aug 20.

Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, and Faculty of Biology, Medicine, and Health, The University of Manchester and Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9PL, United Kingdom; email:

This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012809DOI Listing
January 2019
30 Reads

Polyglutamine Repeats in Neurodegenerative Diseases.

Annu Rev Pathol 2019 01 8;14:1-27. Epub 2018 Aug 8.

Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; email: ,

Among the age-dependent protein aggregation disorders, nine neurodegenerative diseases are caused by expansions of CAG repeats encoding polyglutamine (polyQ) tracts. We review the clinical, pathological, and biological features of these inherited disorders. We discuss insights into pathogenesis gleaned from studies of model systems and patients, highlighting work that informs efforts to develop effective therapies. Read More

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http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387631PMC
January 2019
43 Reads

Pathogenesis of Peripheral T Cell Lymphoma.

Annu Rev Pathol 2018 01;13:293-320

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA; email:

Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including (a) the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; (b) the remodeling of the peritumor microenvironment; and (c) the virus-mediated rewiring of T cell biology. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043821DOI Listing
January 2018
5 Reads

Desmosomes in Human Disease.

Authors:
Nicole A Najor

Annu Rev Pathol 2018 01;13:51-70

Department of Biology, University of Detroit Mercy, Detroit, Michigan 48221; email:

Tissue integrity is crucial for maintaining the homeostasis of living organisms. Abnormalities that affect sites of cell-cell contact can cause a variety of debilitating disorders. The desmosome is an essential cell-cell junctional protein complex in tissues that undergo stress, and it orchestrates intracellular signal transduction. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-044030DOI Listing
January 2018
3 Reads

Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease.

Annu Rev Pathol 2018 01;13:321-350

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria; email:

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on a profound understanding of its pathogenesis to halt disease progression to advanced fibrosis or cirrhosis and cancer. The pathogenesis of NAFLD involves a complex interaction among environmental factors (i. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043617DOI Listing
January 2018
6 Reads

Epithelial Mesenchymal Transition in Tumor Metastasis.

Authors:
Vivek Mittal

Annu Rev Pathol 2018 01;13:395-412

Department of Cardiothoracic Surgery, Department of Cell and Developmental Biology, and Neuberger Berman Foundation Lung Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; email:

Metastasis is the major cause of cancer-related deaths; therefore, the prevention and treatment of metastasis are fundamental to improving clinical outcomes. Epithelial mesenchymal transition (EMT), an evolutionarily conserved developmental program, has been implicated in carcinogenesis and confers metastatic properties upon cancer cells by enhancing mobility, invasion, and resistance to apoptotic stimuli. Furthermore, EMT-derived tumor cells acquire stem cell properties and exhibit marked therapeutic resistance. Read More

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http://www.annualreviews.org/doi/10.1146/annurev-pathol-0201
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http://dx.doi.org/10.1146/annurev-pathol-020117-043854DOI Listing
January 2018
5 Reads

Intrinsic Neuronal Stress Response Pathways in Injury and Disease.

Annu Rev Pathol 2018 01;13:93-116

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030; email:

From injury to disease to aging, neurons, like all cells, may face various insults that can impact their function and survival. Although the consequences are substantially dictated by the type, context, and severity of insult, distressed neurons are far from passive. Activation of cellular stress responses aids in the preservation or restoration of nervous system function. Read More

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http://dx.doi.org/10.1146/annurev-pathol-012414-040354DOI Listing
January 2018
2 Reads

Perspectives from a Pathologist: My Journey on the Path to Women's Health Research, Sex and Gender Policy, and Practice Implications.

Authors:
Vivian W Pinn

Annu Rev Pathol 2018 01;13:1-25

Former Director (Retired), Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland 20892; email:

These words reflect my recollections of major transition points in my life and career: as I first became dedicated to becoming a physician, being introduced to the field of pathology and research, and then transitioning to a somewhat different career focus by becoming the first director of the National Institutes of Health Office of Research on Women's Health. Many of the experiences that I gained during my years in pathology served me well as I made efforts to establish women's health research and sex and gender based studies as scientific endeavors. Participating in research and teaching as an academic pathologist, setting funding priorities, and supporting and encouraging research careers through governmental office programs have been the essence of my more than 50 years as a pathologist and physician. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-044020DOI Listing
January 2018
1 Read

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

Annu Rev Pathol 2018 01;13:379-394

Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA; email: ,

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Read More

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http://www.annualreviews.org/doi/10.1146/annurev-pathol-0512
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http://dx.doi.org/10.1146/annurev-pathol-051217-111018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803388PMC
January 2018
15 Reads

New Insights into Lymphoma Pathogenesis.

Annu Rev Pathol 2018 01 15;13:193-217. Epub 2017 Nov 15.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: ,

Lymphomas represent clonal proliferations of lymphocytes that are broadly classified based upon their maturity (peripheral or mature versus precursor) and lineage (B cell, T cell, and natural killer cell). Insights into the pathogenetic mechanisms involved in lymphoma impact the classification of lymphoma and have significant implications for the diagnosis and clinical management of patients. Serial scientific and technologic advances over the last 30 years in immunology, cytogenetics, molecular biology, gene expression profiling, mass spectrometry-based proteomics, and, more recently, next-generation sequencing have contributed to greatly enhance our understanding of the pathogenetic mechanisms in lymphoma. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043803DOI Listing
January 2018
21 Reads

Cellular and Molecular Mechanisms of Autoimmune Hepatitis.

Annu Rev Pathol 2018 01;13:247-292

Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California 95817, USA; email:

Autoimmune hepatitis is an uncommon idiopathic syndrome of immune-mediated destruction of hepatocytes, typically associated with autoantibodies. The disease etiology is incompletely understood but includes a clear association with human leukocyte antigen (HLA) variants and other non-HLA gene variants, female sex, and the environment. Pathologically, there is a CD4+ T cell-rich lymphocytic inflammatory infiltrate with variable hepatocyte necrosis and subsequent hepatic fibrosis. Read More

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http://dx.doi.org/10.1146/annurev-pathol-020117-043534DOI Listing
January 2018
2 Reads