Publications by authors named "Anthony Chang"

The evaluation and management of renal masses, predominantly of the clear cell renal cell carcinoma subtype, have been evolving over the past several years and demanding greater attention from nephrologists. Oncologic survival of localized tumors approaches 100%, where survival is more closely tied to underlying comorbidities including chronic kidney disease (CKD). Early diagnosis and thus increasing prevalence related to incidental discovery of renal masses allows greater emphasis on nephron-sparing procedures and for residual kidney function preservation.

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Background: In human lupus nephritis (LuN), tubulointerstitial inflammation (TII) is prognostically more important than glomerular inflammation. However, a comprehensive understanding of both TII complexity and heterogeneity is lacking.

Methods: Herein, we used high-dimensional confocal microscopy, spatial transcriptomics and specialized computer vision techniques to quantify immune cell populations and localize these within normal and diseased renal cortex structures.

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Fibroblasts and immune cells coordinate tissue regeneration and necessary scarring after injury. In the brain, fibroblasts are border-enriched cells whose dynamic molecular states and immune interactions after injury remain unclear. Here we define the shared fibroblast-immune response to brain injury.

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Congenital heart disease is a leading cause of preventable death in children, with a disproportionate impact on low- and middle-income countries. Despite progress in treating congenital heart disease globally, significant challenges remain in accessing specialized cardiovascular care, particularly cardiac surgery, in low- and middle-income countries. This review examines current models of assistance and proposes a novel global training program to address these inequities.

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Fibroblasts coordinate the response to tissue injury, directing organ regeneration versus scarring. In the central nervous system (CNS), fibroblasts are uncommon cells enriched at tissue borders, and their molecular, cellular, and functional interactions after brain injury are poorly understood. Here we define the fibroblast response to sterile brain damage across time and space.

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Article Synopsis
  • - The study focuses on improving the analysis of high-content images from multiplexed microscopy to better understand cells within their native tissue, highlighting the need for stronger computational tools to interpret these complex images.
  • - The authors introduce a new method called pseudo-spectral angle mapping (pSAM), which effectively classifies each pixel in high-plex images, enabling better identification of different cell types.
  • - Results demonstrate that pSAM successfully classifies diverse cell types in datasets from colon and kidney biopsies, proving its effectiveness as a versatile tool for analyzing high-plex immunofluorescence data.
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Background: As pediatric hospitals continue to grow in innovation, it is important to create a standardized metric to measure this growth and create a network to encourage further innovation. We worked to classify all pediatric hospitals on a scale of innovation with the goal of encouraging collaboration that can lead to more overall innovation.

Methods: All pediatric hospitals worldwide were ranked on a scale of innovation from 1 to 3, with 1 being the most innovative, or "established," and 3 being the least innovative, or "nascent.

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Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors.

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Article Synopsis
  • E-cigarettes are thought to be safer than regular cigarettes because their liquids don't have known cancer-causing chemicals.
  • However, studies showed that two main ingredients in e-cigarettes, PG/VG and nicotine, can actually help tumors grow and spread more aggressively in test models.
  • Mice exposed to these e-cigarette ingredients developed tumors with a lot of harmful immune cells, but treatment with a specific medicine helped reduce tumor spread without harming the mice.
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Thrombotic microangiopathy (TMA) is a pathological lesion that occurs due to endothelial injury. It can be seen in a heterogenous group of disorders, typically characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. TMA can also be renal limited with no systemic manifestations.

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Commensal microbes have the capacity to affect development and severity of autoimmune diseases. Germ-free (GF) animals have proven to be a fine tool to obtain definitive answers to the queries about the microbial role in these diseases. Moreover, GF and gnotobiotic animals can be used to dissect the complex symptoms and determine which are regulated (enhanced or attenuated) by microbes.

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Artificial intelligence (AI) broadly describes a branch of computer science focused on developing machines capable of performing tasks typically associated with human intelligence. Those who connect AI with the world of science fiction may meet its growing rise with hesitancy or outright skepticism. However, AI is becoming increasingly pervasive in our society, from algorithms helping to sift through airline fares to substituting words in emails and SMS text messages based on user choices.

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Article Synopsis
  • The rise of advanced microscopy has allowed for the examination of cells in their natural environments, revealing new insights into human diseases.
  • Current computational methods for analyzing these detailed images are still developing, highlighting the need for improved tools to evaluate cellular structures accurately.
  • The authors introduced a new technique called pseudospectral angle mapping (pSAM), which effectively analyzes high-plex immunofluorescence images, providing meaningful insights into different cell types in tissue samples, as demonstrated through various patient biopsy datasets.
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  • This study tested how well a blood test called Tutivia can predict if a kidney transplant will be rejected early on.
  • 151 kidney transplant patients, mostly around 53 years old and mostly male, were watched to see how well Tutivia worked.
  • Tutivia was found to be better than just looking at one kidney function test, helping doctors predict rejection more accurately without invasive procedures.
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As life expectancy continues to rise, age-related diseases are becoming more prevalent. For example, proteinuric glomerular diseases typified by podocyte injury have worse outcomes in the elderly compared with young patients. However, the reasons are not well understood.

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Early-stage organ transplant rejection can be difficult to detect. Percutaneous biopsies occur infrequently and are risky, and measuring biomarker levels in blood can lead to false-negative and -positive outcomes. We developed an implantable bioelectronic system capable of continuous, real-time, long-term monitoring of the local temperature and thermal conductivity of a kidney for detecting inflammatory processes associated with graft rejection, as demonstrated in rat models.

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  • This study investigates the molecular characteristics of proliferative lupus nephritis (LN) through imaging mass cytometry, focusing on the spatial profiles of 50 proteins in LN and healthy kidneys.
  • Proliferative LN is characterized by podocyte loss, significant immune cell infiltration (primarily memory T-cells and macrophages), and notable changes in both glomeruli and tubulointerstitial areas.
  • The research highlights the role of macrophages in the disease and identifies features such as fibronectin presence and epithelial-to-mesenchymal transition in tubular cells, showcasing the effectiveness of IMC in understanding the complex architecture of LN at the protein level.
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The decrease in the podocyte's lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging.

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Increasing survivorship in kidney cancer patients has shifted treatment strategies to optimize renal function preservation. In 2010, the College of American Pathologists (CAP) updated their synoptic reporting guidelines for tumor nephrectomies to require evaluation of the nonneoplastic kidney parenchyma. We conducted this study to understand current practice behaviors regarding the evaluation of the nonneoplastic kidney parenchyma in tumor nephrectomy specimens.

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Group 2 innate lymphoid cells (ILC2s) cooperate with adaptive Th2 cells as key organizers of tissue type 2 immune responses, while a spectrum of innate and adaptive lymphocytes coordinate early type 3/17 immunity. Both type 2 and type 3/17 lymphocyte associated cytokines are linked to tissue fibrosis, but how their dynamic and spatial topographies may direct beneficial or pathologic organ remodelling is unclear. Here we used volumetric imaging in models of liver fibrosis, finding accumulation of periportal and fibrotic tract IL-5 lymphocytes, predominantly ILC2s, in close proximity to expanded type 3/17 lymphocytes and IL-33 niche fibroblasts.

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Context.—: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease.

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