Kinetic inductance current sensor for visible to near-infrared wavelength transition-edge sensor readout.

Single-photon detectors based on the superconducting transition-edge sensor are used in a number of visible to near-infrared applications, particularly for photon-number-resolving measurements in quantum information science. To be practical for large-scale spectroscopic imaging or photonic quantum computing applications, the size of visible to near-infrared transition-edge sensor arrays and their associated readouts must be increased from a few pixels to many thousands. In this manuscript, we introduce the kinetic inductance current sensor, a scalable readout technology that exploits the nonlinear kinetic inductance in a superconducting resonator to make sensitive current measurements.

Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities.

The lymphatic vascular system spans nearly every organ in the body and serves as an important network that maintains fluid, metabolite, and immune cell homeostasis. Recently, there has been a growing interest in the role of lymphatic biology in chronic disorders outside the realm of lymphatic abnormalities, lymphedema, or oncology, such as cardiovascular-kidney-metabolic syndrome (CKM). We propose that enhancing lymphatic function pharmacologically may be a novel and effective way to improve quality of life in patients with CKM syndrome by engaging multiple pathologies at once throughout the body.

Nanoscale Three-Dimensional Imaging of Integrated Circuits Using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer.

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools.

Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.

Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known.

Patch Testing With Nickel, Cobalt, and Chromium in Patients With Suspected Allergic Contact Dermatitis.

Allergic contact dermatitis is frequently caused by metals, including multiple metals simultaneously. To assess characteristics and associations of positive and clinically relevant patch test (PT) reactions with solitary and concurrent metal sensitization. A retrospective analysis of PT results for nickel, cobalt, and/or chromium from the North American Contact Dermatitis Group between 2001 and 2018 ( = 43,522).

Loss of cis-PTase function in the liver promotes a highly penetrant form of fatty liver disease that rapidly transitions to hepatocellular carcinoma.

Obesity-linked fatty liver is a significant risk factor for hepatocellular carcinoma (HCC); however, the molecular mechanisms underlying the transition from non-alcoholic fatty liver disease (NAFLD) to HCC remains unclear. The present study explores the role of the endoplasmic reticulum (ER)-associated protein NgBR, an essential component of the cis-prenyltransferases (cis-PTase) enzyme, in chronic liver disease. Here we show that genetic depletion of NgBR in hepatocytes of mice (N-LKO) intensifies triacylglycerol (TAG) accumulation, inflammatory responses, ER/oxidative stress, and liver fibrosis, ultimately resulting in HCC development with 100% penetrance after four months on a high-fat diet.

TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes.

The endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism; however, the function and regulation of elevated mitochondrial metabolism in EC in response to proinflammatory cytokines remain unclear. Studies using high-resolution metabolomics and C-glucose and C-glutamine labeling flux techniques showed that pyruvate dehydrogenase activity (PDH) and oxidative tricarboxylic acid cycle (TCA) flux are elevated in human umbilical vein ECs in response to overnight (16 h) treatment with TNFα (10 ng/mL).

SREBP2 regulates the endothelial response to cytokines via direct transcriptional activation of KLF6.

The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and is central to the mechanism of action of lipid-lowering drugs, such as statins, which are responsible for the largest overall reduction in cardiovascular risk and mortality in humans with atherosclerotic disease. Recently, SREBP2 has been implicated in leukocyte innate and adaptive immune responses by upregulation of cholesterol flux or direct transcriptional activation of pro-inflammatory genes. Here, we investigate the role of SREBP2 in endothelial cells (ECs), since ECs are at the interface of circulating lipids with tissues and crucial to the pathogenesis of cardiovascular disease.

Patch Testing With Cobalt in Adults: A North American Contact Dermatitis Group Experience, 2001-2018.

Cobalt is a recognized cause of allergic contact dermatitis (ACD); however, detailed information on patient characteristics, sites, and sources is lacking. The aim of the study is to assess trends in patch test reactions to cobalt and associated patient characteristics, common sources, and body sites affected. The study used a retrospective analysis of adult patients who were patch tested to cobalt by the North American Contact Dermatitis Group between 2001 and 2018 (n = 41,730).

Oral spleen tyrosine kinase/Janus Kinase inhibitor gusacitinib for the treatment of chronic hand eczema: Results of a randomized phase 2 study.

Background: Gusacitinib is an oral inhibitor of Janus and Spleen tyrosine kinases.

Methods: The efficacy and safety of gusacitinib were evaluated in a double-blind, placebo-controlled, multicenter, phase 2 study in 97 chronic hand eczema patients randomized (1:1:1) to placebo or gusacitinib (40 or 80 mg) for 12 weeks (part A). Then, in part B (through week 32), the patients received gusacitinib.

A tabletop X-ray tomography instrument for nanometer-scale imaging: reconstructions.

We show three-dimensional reconstructions of a region of an integrated circuit from a 130 nm copper process. The reconstructions employ x-ray computed tomography, measured with a new and innovative high-magnification x-ray microscope. The instrument uses a focused electron beam to generate x-rays in a 100 nm spot and energy-resolving x-ray detectors that minimize backgrounds and hold promise for the identification of materials within the sample.

Patch Testing With Benzophenone-3 and -4: The North American Contact Dermatitis Group Experience, 2013-2020.

Benzophenone (BZP)-3 and BZP-4 are ultraviolet (UV) absorbers used in sunscreens and personal care products (PCPs) and may cause allergic contact dermatitis. To characterize positive patch test reactions to BZP-3 (10% in petrolatum [pet]) and BZP-4 (2% pet) in a screening allergen series. Retrospective analysis of patients tested to BZP-3 and BZP-4 was conducted by the North American Contact Dermatitis Group from 2013 to 2020.

North American Contact Dermatitis Group Patch Test Results: 2019-2020.

Patch testing is an important diagnostic tool for assessment of allergic contact dermatitis (ACD). This study documents the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2019, to December 31, 2020. At 13 centers in North America, patients were tested in a standardized manner with a screening series of 80 allergens, and, as indicated, supplemental allergens.

Impact of Crisaborole on Sleep Outcomes in Pediatric Patients with Mild-to-Moderate Atopic Dermatitis.

Introduction: Using data from three clinical trials, the effect of crisaborole treatment on sleep outcomes for pediatric patients with atopic dermatitis (AD) and their families was examined.

Methods: This analysis comprised patients aged 2 to < 16 years from the double-blind phase 3 CrisADe CORE 1 (NCT02118766) and CORE 2 (NCT02118792) studies, families of patients aged 2 to < 18 years from CORE 1 and CORE 2, and patients aged 3 months to < 2 years from the open-label phase 4 CrisADe CARE 1 study (NCT03356977), all with mild-to-moderate AD who received crisaborole ointment 2% twice daily for 28 days. Sleep outcomes were assessed via the Children's Dermatology Life Quality Index and Dermatitis Family Impact questionnaires in CORE 1 and CORE 2 and the Patient-Oriented Eczema Measure questionnaire in CARE 1.

Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling.

Background: Cross-talk between sterol metabolism and inflammatory pathways has been demonstrated to significantly affect the development of atherosclerosis. Cholesterol biosynthetic intermediates and derivatives are increasingly recognized as key immune regulators of macrophages in response to innate immune activation and lipid overloading. 25-Hydroxycholesterol (25-HC) is produced as an oxidation product of cholesterol by the enzyme cholesterol 25-hydroxylase (CH25H) and belongs to a family of bioactive cholesterol derivatives produced by cells in response to fluctuating cholesterol levels and immune activation.

Inflammatory stress signaling via NF-B alters accessible cholesterol to upregulate SREBP2 transcriptional activity in endothelial cells.

There is a growing appreciation that a tight relationship exists between cholesterol homeostasis and immunity in leukocytes; however, this relationship has not been deeply explored in the vascular endothelium. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors to activate and recruit circulating leukocytes to the site of injury and aberrant activation of ECs leads to inflammatory based diseases, such as multiple sclerosis and atherosclerosis. Here, we studied the role of cholesterol and a key transcription regulator of cholesterol homeostasis, SREBP2, in the EC responses to inflammatory stress.

Hand and foot dermatitis in patients referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

Background: Dermatitis localized to hands (HD), feet (FD), or both hands and feet (HFD) has multiple etiologies, including atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis. Unfortunately, little is known about clinical differences between patients with HD, FD, and HFD.

Objective: To characterize differences in demographics, etiology, and patch testing results among patients presenting with HD, FD, or HFD referred for patch testing.

Patch testing with cobalt in children and adolescents: North American contact dermatitis group experience, 2001-2018.

Background: Allergic contact dermatitis (ACD) to cobalt is more common in children and adolescents than adults. However, detailed information on sites and sources of cobalt ACD is limited.

Objectives: To assess trends in positive and clinically relevant patch test reactions to cobalt in children and associated patient characteristics, common sources and body sites affected.

Lanolin Allergic Reactions: North American Contact Dermatitis Group Experience, 2001 to 2018.

Background: Lanolin is an important cause of allergic contact dermatitis.

Objectives: The aims of this study were to describe the epidemiology of lanolin allergy and to assess trends in patch test reactions to lanolin over time.

Methods: This study used a retrospective analysis of patients patch tested with lanolin alcohol 30% or Amerchol L-101 50% in petrolatum by the North American Contact Dermatitis Group between 2001 and 2018 (n = 43,691).

Occupational Contact Dermatitis in Dental Personnel: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001 to 2018.

Background: Dental personnel are at risk of developing occupational contact dermatitis.

Objectives: The aims of the study were to determine prevalence of occupational contact dermatitis in dental personnel referred for patch testing and to characterize relevant allergens and sources.

Methods: The study used a retrospective, cross-sectional analysis of the North American Contact Dermatitis Group (NACDG) data, 2001-2018.

Shoe Allergens: A Retrospective Analysis of Cross-sectional Data From the North American Contact Dermatitis Group, 2005-2018.

Background: Shoe contact allergy can be difficult to diagnose and manage.

Objective: The aim of the study was to characterize demographics, clinical characteristics, patch test results, and occupational data for the North American Contact Dermatitis Group patients with shoe contact allergy.

Methods: This is a retrospective study of 33,661 patients, patch tested from 2005 to 2018, with a shoe source, foot as 1 of 3 sites of dermatitis, and final primary diagnosis of allergic contact dermatitis.