The adoption of chronic implantable peripheral nerve-based prosthetic devices is currently hampered by the lack of a highly integrated neural signal acquisition system-on-chip (SoC). We report a ...ten-channel peripheral nervous system (PNS) electroneurogram (ENG) signal acquisition SoC within an implantable package. Requiring only four off-chip capacitors, this SoC can be co-encapsulated with flexible nerve electrodes and a resonant coil antenna to form a 3.4 cm 3 and 3.9 g implantable device for chronic ENG acquisition. This SoC is inductively powered and controlled through a resonant coil at 22 MHz and transmits the digitized neural signal through a near-infrared LED (NIR-LED). Fabricated in 0.18-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> CMOS, each amplifier channel exhibits an input referred noise of 1.9 <inline-formula> <tex-math notation="LaTeX">\mu \text{V}_{\mathbf {rms}} </tex-math></inline-formula> and a noise efficiency factor (NEF) of 4.0 within the signal bandwidth of 5.5 kHz. Each amplifier channel within the SoC is digitized with 10-bit resolution at 17.5 ksps, and the total power consumption (SoC and NIR-LED) is 4.4 mW when the NIR-LED is driven at 3 Mb/s. An electrode impedance measurement circuit with <10% magnitude and <8° angle error for measuring impedances up to 1 <inline-formula> <tex-math notation="LaTeX">\text{M}\Omega </tex-math></inline-formula> is also incorporated in this SoC. This wireless, low noise ENG acquisition SoC package has been validated in vivo while implanted on a rodent to acquire ENG from its sciatic nerve.
Background: Although chronic infection with hepatitis B virus (HBV) has been established as a cause of hepatocellular carcinoma (HCC), the roles of viral load and HBV genotype remain unclear. ...Methods: From 1988 through 1992, baseline blood samples were collected from 4841 Taiwanese men who were HBV carriers but had not been diagnosed with HCC. We used real-time polymerase chain reaction assays of plasma DNA samples to quantify HBV DNA levels (a measure of viral load) and determine HBV genotypes for 154 case patients who were diagnosed with HCC during 14 years of follow-up and 316 control subjects. Unconditional logistic regression was used to assess odds ratios (ORs) of HCC for HBV-related factors. All statistical tests were two-sided. Results: The risk of HCC increased with increasing HBV viral load (adjusted OR for the highest versus the lowest quintile of HBV DNA copies/mL = 7.26, 95% confidence interval CI = 3.54 to 14.89; Ptrend<.001). Genotype C HBV was associated with an increased risk of HCC compared with other HBV genotypes (adjusted OR = 5.11, 95% CI = 3.20 to 8.18). Both viral load and genotype were positively associated with HCC within 10-year age categories among subjects aged 30 years old to older than 60 years. Genotype C HBV was associated with increased viral load, and associations of HBV genotype and viral load with HCC risk were additive. The adjusted OR of HCC for those carrying genotype C HBV and with viral load in the highest quintile was 26.49 (95% CI = 10.41 to 67.42) compared with HBV carriers with other HBV genotypes and viral load in the lowest two quintiles. Conclusions: Measurements of HBV viral load and genotype may help to define which male HBV carriers aged 30 years or older are at high risk for HCC.
Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a ...source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with ...better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.
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•Both D3 and M3-UM divide into molecularly distinct subsets with different outcomes•Poor-prognosis M3-UM are characterized by a global DNA methylation pattern•Poor-prognosis M3-UM subsets have distinct genomic, signaling, and immune profiles•EIF1AX and SRSF2/SF3B1 mutant D3-UM have different genomic/DNA methylation profiles
Robertson et al. analyze 80 uveal melanomas (UM) and divide poor-prognosis monosomy 3 UM into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. Somatic copy number changes and DNA methylation profiles separate better-prognosis disomy 3 UM into low or intermediate risk.
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