Publications by authors named "Kung A"

Objective: To examine the extent of segregation between hospitals for Medicare beneficiaries by race, ethnicity, and dual-eligible status over time.

Data Sources And Study Setting: We used Medicare inpatient hospital provider data for fee-for-service (FFS) beneficiaries, and the Dartmouth Atlas of Health Care from 2013 to 2021 nationwide, for hospital referral regions (HRRs), and for and hospital service areas (HSAs).

Study Design: We conducted time trend analysis with dissimilarity indices (DIs) for Black (DI-Black), Hispanic (DI-Hispanic), non-White (including Black, Hispanic, and other non-White) (DI-non-White), and dual-eligible (DI-Dual) beneficiaries.

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Large-scale combination drug screens are generally considered intractable due to the immense number of possible combinations. Existing approaches use ad hoc fixed experimental designs then train machine learning models to impute unobserved combinations. Here we propose BATCHIE, an orthogonal approach that conducts experiments dynamically in batches.

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Autophagy is a key biological process that has proven extremely difficult to detect noninvasively. To address this, an autophagy detecting nanoparticle (ADN) was recently developed, consisting of an iron oxide nanoparticle decorated with cathepsin-cleavable arginine-rich peptides bound to the near-infrared fluorochrome Cy5.5.

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Programs for preclinical testing of targeted cancer agents in murine models of childhood cancers have been supported by the National Cancer Institute (NCI) since 2004. These programs were established to work collaboratively with industry partners to address the paucity of targeted agents for pediatric cancers compared with the large number of agents developed and approved for malignancies primarily affecting adults. The distinctive biology of pediatric cancers and the relatively small numbers of pediatric cancer patients are major challenges for pediatric oncology drug development.

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Background/objectives: There has been limited evidence on the long-term impacts of coffee intake on health. We aimed to investigate the association between coffee intake and the incidence of diseases and mortality risk over 20 years among community-dwelling Chinese adults.

Methods: Participants were from the Hong Kong Osteoporosis Study who attended baseline assessments during 1995-2010.

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Early-career surgeons must be exposed to a sufficient number of surgical cases of varying complexity in a mentored environment to allow them to solidify, sustain and build on the skills gained in training. Decreased operative volumes at military treatment facilities and assignments that do not include strong mentoring environments can place military surgeons at a disadvantage relative to their civilian counterparts during this critical time following training. The challenge of lower operative volumes in the current interwar lull has been exacerbated by the decline in beneficiary care conducted within the Military Healthcare System.

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Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein.

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Objectives: Type 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM

Methods: This is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study.

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The Azotobacter vinelandii FeSII protein forms an oxygen-resistant complex with the nitrogenase MoFe and Fe proteins. FeSII is an adrenodoxin-type ferredoxin that forms a dimer in solution. Previously, the crystal structure was solved [Schlesier et al.

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Tumors frequently harbor isogenic yet epigenetically distinct subpopulations of multi-potent cells with high tumor-initiating potential-often called Cancer Stem-Like Cells (CSLCs). These can display preferential resistance to standard-of-care chemotherapy. Single-cell analyses can help elucidate Master Regulator (MR) proteins responsible for governing the transcriptional state of these cells, thus revealing complementary dependencies that may be leveraged via combination therapy.

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Despite the potential of targeted epigenetic therapies, most cancers do not respond to current epigenetic drugs. The Polycomb repressive complex EZH2 inhibitor tazemetostat was recently approved for the treatment of -deficient epithelioid sarcomas, based on the functional antagonism between PRC2 and loss of SMARCB1. Through the analysis of tazemetostat-treated patient tumors, we recently defined key principles of their response and resistance to EZH2 epigenetic therapy.

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Article Synopsis
  • The rise of autoimmune diseases calls for new therapies, but there's a lack of long-term evaluation methods for these treatments.
  • Researchers used advanced techniques to analyze the unique patterns of autoantibodies in individuals, identifying stable "autoreactomes" that serve as immunological fingerprints.
  • Their findings suggest that therapies targeting B cell maturation antigen (BCMA) can significantly change these autoreactomes, implying that BCMA-based treatments might be effective for difficult-to-treat autoimmune conditions.
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Context: Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown.

Objective: This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS).

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Article Synopsis
  • A 14-year-old girl with a type of cancer called T-ALL received a special transplant, but it took a long time for her body to start making new blood cells.
  • The doctors tested a medication she was given, called daratumumab, to see if it was affecting her recovery.
  • They found that the daratumumab stayed in her body longer than expected, which might have caused the delays, and they are planning to research how to use this medication better for kids with cancer.
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Background Aims: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell-depleted (EX-VIVO-TCD) HCT.

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Unlabelled: Epigenetic dependencies have become evident in many cancers. On the basis of antagonism between BAF/SWI-SNF and PRC2 in SMARCB1-deficient sarcomas, we recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown.

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Article Synopsis
  • The rise of autoimmune diseases and related disorders is significant globally, but the underlying causes are still unclear, and there is a lack of comprehensive methods to evaluate new immunomodulatory treatments over time.
  • Researchers used advanced PhIP-Seq technology to study how autoantibody profiles, which are unique to each individual, change in health and disease, identifying a stable immunological fingerprint known as the "autoreactome."
  • The study found that certain therapies, specifically those targeting B-Cell Maturation Antigen (BCMA), have a major impact on autoantibody profiles, while others like anti-CD19 and CD-20 have minimal influence, suggesting BCMA-targeted therapies may be more effective in treating autoantibody-mediated diseases.
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Network properties account for the complex relationship between genes, making it easier to identify complex patterns in their interactions. In this work, we leveraged these network properties for dual purposes. First, we clustered pediatric sarcoma tumors using network information flow as a similarity metric, computed by the Wasserstein distance.

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The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross-neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected early in the COVID-19 pandemic, before widespread rollout of SARS-CoV-2 vaccines.

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Autoimmunity is characterized by loss of tolerance to tissue-specific as well as systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics of a murine proteome-wide library for phage display immunoprecipitation and sequencing (PhIP-seq) in profiling mouse autoantibodies. This library was validated using 7 genetically distinct mouse lines across a spectrum of autoreactivity.

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Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS).

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Introduction And Objective: The risk of seizure in offspring following prenatal exposure to levothyroxine is not well investigated. This study aimed to evaluate the association between levothyroxine treatment among pregnant women and the risk of seizure in their offspring.

Methods: This population-based cohort study included all pregnant women who delivered a live birth between January 2001 to January 2018, with a follow-up to December 2020, using data from the Hong Kong Clinical Data Analysis and Reporting System.

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Unlabelled: Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma.

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Diffuse large B-cell lymphoma (DLBCL) remains a formidable diagnosis in need of new treatment paradigms. In this work, we elucidated an opportunity for therapeutic synergy in DLBCL by reactivating tumor protein p53 with a stapled peptide, ATSP-7041, thereby priming cells for apoptosis and enhancing their sensitivity to BCL-2 family modulation with a BH3-mimetic, ABT-263 (navitoclax). While this combination was highly effective at activating apoptosis in DLBCL , it was highly toxic , resulting in a prohibitively narrow therapeutic window.

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