Publications by authors named "Michael Ke"

Article Synopsis
  • Innate immune activation is essential for the onset of liver inflammation in nonalcoholic steatohepatitis (NASH), with unclear mechanisms of how certain immune molecules detect signals related to fat and inflammation.
  • High-fat diets trigger oxidative stress, activating specific signaling pathways (Foxo1, YAP, Notch1) in liver macrophages, while removing Foxo1 reduced inflammation and fibrosis in the liver.
  • The study reveals that the interplay between Foxo1, YAP, and Notch1 is crucial for managing lipid metabolism and immune responses during NASH, highlighting their roles as regulatory factors in disease progression.
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Background And Aims: The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive.

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Background & Aims: The stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) pathway is vital in mediating innate immune and inflammatory responses during oxidative/endoplasmic reticulum (ER) stress. However, it remains unknown whether macrophage thioredoxin-interacting protein (TXNIP) may regulate TBK1 function and cell death pathways during oxidative/ER stress.

Methods: A mouse model of hepatic ischaemia/reperfusion injury (IRI), the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific TXNIP knockout (TXNIP) and TXNIP-proficient (TXNIP) mice.

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Coccidioidomycosis (CM) is a fungal infection endemic to the southwestern United States with a wide range of clinical presentations depending on the infected organ systems. Most infections are asymptomatic. Coccidioidomycosis causes a primary pulmonary infection and when symptoms occur, they most often resemble community-acquired pneumonia.

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North Carolina's transformation to Medicaid managed care is projected to improve health outcomes for the state's Medicaid population and elevate patient experience by integrating the social determinants of health into the state's care model and aligning state, provider, and health plan goals. This will increase access to timely, localized care services for members.

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Background And Objective: Current standard practice guidelines recommend ICU admission for ischemic stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). More recently, the trend in stroke care is to broaden eligibility for IV thrombolysis. Two examples are a more liberal inclusion criteria known as SMART criteria (sIV-tPA), and the transfer of patients to comprehensive stroke centers (CSC).

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Objectives: To investigate the effect of managed care organization (MCO)-implemented postdischarge engagement, supported by other broadly focused interventions, on 30-day hospital readmissions in 6 at-risk Medicaid populations.

Study Design: Prospective cohort study.

Methods: One-year follow-up analysis of member claims data was performed following an intervention period from January 1, 2014, to December 31, 2014.

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Objective: To measure the effectiveness of managed care-led interventions in Medicaid subjects with asthma on medication adherence and acute hospitalization in Pennsylvania.

Methods: A total of 3589 members (age range, 5-64 years) served by two Pennsylvania-based Medicaid managed care plans (southeastern Pennsylvania [SEPA] and Lehigh-Capital/New West Pennsylvania [LCNWPA]) with low adherence rates (proportion of days covered [PDC]; 20%-67%) for asthma controller prescription fills in 2012 were guided through a care continuum by a comprehensive asthma strategy, consisting of adherence-improvement interventions (grouped as general intervention [GI] or personalized intervention [PI] for higher-risk subjects). Medication adherence and acute hospitalization rates (emergency department [ED] and inpatient [IP]) were compared at baseline versus one-year post-intervention using paired t-test or signed-rank tests.

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Little is known about exposure to pathogenic bacteria among industrial laundry workers who work with soiled clinical linen. To study worker exposures, an assessment of surface contamination was performed at an industrial laundry facility serving hospitals in Seattle, WA, USA. Surface swab samples (n = 240) from the environment were collected during four site visits at 3-month intervals.

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Article Synopsis
  • Notch signaling is important for regulating immune cell development and response during inflammation, particularly in liver ischemia and reperfusion (IR) injury.
  • Removing the Notch1 gene in myeloid cells leads to worse liver damage and higher inflammation markers compared to normal mice, indicating its protective role.
  • Disruption of specific signaling pathways (like JSAP1 and ROCK1) linked to Notch1 deficiency suggests that this signaling network plays a crucial role in liver immune responses during injury.
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Objective: To investigate the relationship between acute perfusion-weighted imaging (PWI) lesions occurring within the first hours after a TIA or a minor brain infarction (BI) and the incidence of new BI detected on a systematic MRI at 1 week.

Methods: Consecutive patients who experienced a TIA or BI with a neurologic deficit that lasted <24 hours, did not receive any revascularization therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid-attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were enrolled. Investigators blinded to clinical information independently assessed the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and FLAIR.

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Article Synopsis
  • Experimental liver injury from acetaminophen involves direct damage from toxic metabolites and immune cell activation.*
  • The study shows that Notch signaling influences innate immune responses during liver injury, affecting inflammation and cell death.*
  • Blocking Notch signaling worsens liver damage, while TLR4 knockout mice demonstrate reduced damage, highlighting the potential for new therapeutic approaches targeting Notch in liver inflammation.*
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The phosphatase and tensin homolog (PTEN) deleted on chromosome 10 plays an important role in regulating T cell activation during inflammatory response. Activation of β-catenin is crucial for maintaining immune homeostasis. This study investigates the functional roles and molecular mechanisms by which PTEN-β-catenin signaling promotes regulatory T cell (Treg) induction in a mouse model of liver ischemia/reperfusion injury (IRI).

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Background: Enterococcus spp. are a normal part of the gastrointestinal tract of humans and animals. They are also important pathogens, being responsible for 14% of US nosocomial infections from 2007 to 2010.

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Article Synopsis
  • - The study examines the role of heat shock transcription factor 1 (HSF1) and its interaction with β-catenin in regulating the NLRP3 inflammasome during liver injury caused by ischemia/reperfusion (I/R).
  • - Mice lacking myeloid HSF1 showed increased liver damage and inflammation, linked to heightened levels of XBP1 and NLRP3, indicating that HSF1 typically acts to protect against such injuries by modulating immune responses.
  • - The findings suggest that HSF1 promotes β-catenin activation, which inhibits the XBP1 pathway; this interplay is crucial for controlling NLRP3 activation and overall inflammatory responses in the liver.
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Objectives: MDR MRSA isolates cultured from primates, their facility and primate personnel from the Washington National Primate Research Center were characterized to determine whether they were epidemiologically related to each other and if they represented common local human-associated MRSA strains.

Methods: Human and primate nasal and composite environmental samples were collected, enriched and selected on medium supplemented with oxacillin and polymyxin B. Isolates were biochemically verified as Staphylococcus aureus and screened for the mecA gene.

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Aim: Examine a clinical laundry facility for the presence of methicillin-resistant Staphylococcus aureus (MRSA) on environmental surfaces and among personnel.

Methods: Nasal and face samples along with surface samples were collected four times in 2015. MRSA isolates were confirmed using standardized biochemical assays and molecular characterization.

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For learning to occur through trial and error, the nervous system must effectively detect and encode performance errors. To examine this process, we designed a set of oculomotor learning tasks with more than one visual object providing potential error cues, as would occur in a natural visual scene. A task-relevant visual target and a task-irrelevant visual background both influenced vestibulo-ocular reflex learning in rhesus monkeys.

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Objectives: To evaluate the effects of a collaborative pharmacy benefits manager (PBM)/ health plan-administered drug therapy management (DTM) program on healthcare utilization and costs in patients with diabetes treated with polypharmacy.

Study Design: Retrospective quasi-experimental design with comparison group.

Methods: This DTM program was a collaborative effort between the PBM, PerformRx, and the care management departments of Keystone First (KF) and AmeriHealth Caritas Pennsylvania (ACP) care management departments, targeting patients with diabetes using >15 medications.

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In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve.

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Guiding of neuronal cells on surfaces is required for the investigation of fundamental aspects of neurobiology, for tissue engineering, and for numerous bioelectronic applications. A modular method to establish nanostructured chemical templates for local deposition of gold nanoparticles is presented. A process comprising nanoimprint lithography, silanization, lift-off, and gold nanoparticle immobilization is used to fabricate the particle patterns.

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Actin-myosin contractility modulates focal adhesion assembly, stress fiber formation, and cell migration. We analyzed the contributions of contractility to fibroblast adhesion strengthening using a hydrodynamic adhesion assay and micropatterned substrates to control cell shape and adhesive area. Serum addition resulted in adhesion strengthening to levels 30-40% higher than serum-free cultures.

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Background Information: FAK (focal adhesion kinase), an essential non-receptor tyrosine kinase, plays pivotal roles in migratory responses, adhesive signalling and mechanotransduction. FAK-dependent regulation of cell migration involves focal adhesion turnover dynamics as well as actin cytoskeleton polymerization and lamellipodia protrusion. Whereas roles for FAK in migratory and mechanosensing responses have been established, the contribution of FAK to the generation of adhesive forces is not well understood.

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The climbing fiber input to the cerebellum from the inferior olive is thought to act as a teacher whose activity controls the induction of motor learning. We designed training conditions that did not elicit instructive signals in the climbing fibers, but nevertheless induced robust and consistent motor learning in the vestibulo-ocular reflex of rhesus monkeys. Our results indicate that instructive signals in the climbing fibers are not necessary for cerebellum-dependent learning.

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Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate.

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