Artificial intelligence (AI) systems have increasingly achieved expert-level performance in medical imaging applications. However, there is growing concern that such AI systems may reflect and ...amplify human bias, and reduce the quality of their performance in historically under-served populations such as female patients, Black patients, or patients of low socioeconomic status. Such biases are especially troubling in the context of underdiagnosis, whereby the AI algorithm would inaccurately label an individual with a disease as healthy, potentially delaying access to care. Here, we examine algorithmic underdiagnosis in chest X-ray pathology classification across three large chest X-ray datasets, as well as one multi-source dataset. We find that classifiers produced using state-of-the-art computer vision techniques consistently and selectively underdiagnosed under-served patient populations and that the underdiagnosis rate was higher for intersectional under-served subpopulations, for example, Hispanic female patients. Deployment of AI systems using medical imaging for disease diagnosis with such biases risks exacerbation of existing care biases and can potentially lead to unequal access to medical treatment, thereby raising ethical concerns for the use of these models in the clinic.
Summary
Background
Dupilumab a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13 is approved for patients aged ≥ 12 years with inadequately controlled, ...moderate‐to‐severe atopic dermatitis (AD). Dupilumab trials of up to 52 weeks demonstrated efficacy and a favourable safety profile in patients with moderate‐to‐severe AD inadequately controlled with topical medications.
Objectives
To further characterize the safety of dupilumab by evaluating clinical laboratory findings from three randomized, double‐blinded, placebo‐controlled phase III trials (LIBERTY AD SOLO 1 & 2 and LIBERTY AD CHRONOS).
Methods
Patients were randomized 1 : 1 : 1 (SOLO 1 & 2) or 3 : 1 : 3 (CHRONOS) for 16 and 52 weeks, respectively, to dupilumab weekly, every 2 weeks or placebo. CHRONOS patients received a standardized concomitant topical corticosteroid regimen. Laboratory outcomes were summarized descriptively in 1376 patients from SOLO 1 & 2 and 740 from CHRONOS.
Results
Treatment groups had similar results in baseline laboratory parameters. Platelets and neutrophils showed mild decreases from baseline in dupilumab vs. placebo groups. Some dupilumab‐treated patients had small transient increases in eosinophils. Grade 3 eosinophilia was reported in < 1% of dupilumab‐treated and placebo‐treated patients; no adverse events were associated with eosinophilia. Lactate dehydrogenase levels decreased from baseline during dupilumab treatment in all trials. No clinically meaningful changes were observed between treatment groups in other haematology, chemistry or urinalysis parameters.
Conclusions
There were no clinically important changes in routine laboratory parameters that could be attributed to dupilumab. This study supports the use of dupilumab as a systemic treatment for moderate‐to‐severe AD that does not require laboratory monitoring.
What's already known about this topic?
Long‐term treatment of atopic dermatitis (AD) with conventional immunosuppressive agents is limited by the risk of significant side‐effects and a need for repeated tests to monitor haematological and/or organ (e.g. liver, kidney) toxicities.
Dupilumab a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13 is approved for the treatment of patients with inadequately controlled, moderate‐to‐severe AD.
In 16‐week and 52‐week studies, dupilumab demonstrated a positive risk/benefit profile in moderate‐to‐severe AD.
What does this study add?
This study is the first comprehensive analysis of dupilumab laboratory safety data of the 16‐week SOLO 1 & 2 (pooled N = 1376) and 52‐week CHRONOS (N = 740) trials, demonstrating an absence of clinically important changes in haematology, serum chemistry and urinalysis parameters in patients with moderate‐to‐severe AD treated with dupilumab.
Our data support the use of dupilumab as a systemic treatment for the long‐term management of moderate‐to‐severe AD without routine laboratory monitoring in clinical practice.
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While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future ...SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.
This study discusses the function of citrate ions in the synthesis of silver nanoplates through a synergetic reduction approach in ambient conditions. It was found that the citrate ions can play ...multiple roles in the synthesis process, including a reducing agent, a stabilizer, and a complex agent, and they show some unique features under the reported conditions. The reducing ability of these citrate ions was shown to be weaker than that of sodium borohydride and/or l-ascorbic acid used in the same system. The stability in the shape/size control of silver particles is weaker than that of other surfactants tested in the present system, such as bis(2-ethylhexyl)sulfosuccinate (AOT) and thiols. Citrate ions could form a silver complex with silver ions as Ag2 +···citrate or Ag3(C6H5O7) n+13n− , as confirmed by electrospray ionization (ESI) mass spectrometry and the kinetic analysis that the molar ratio of citric acid or sodium citrate to silver ions can greatly influence the reaction rate and, hence, the particle growth of silver nanoparticles. Such a complexing effect is further confirmed by the use of chelating ions (e.g., Fe(CN)64−) to form Ag n Fe(CN)6 n−4, which can largely influence the synthesis of silver nanoparticles. These results show some formation results of generating silver nanoplates involving citrate ions, which are useful in the shape-controlled synthesis of other metallic nanoparticles with desirable functionalities.
This study presents the role of reaction temperature in the formation and growth of silver nanoparticles through a synergetic reduction approach using two or three reducing agents simultaneously. By ...this approach, the shape-/size-controlled silver nanoparticles (plates and spheres) can be generated under mild conditions. It was found that the reaction temperature could play a key role in particle growth and shape/size control, especially for silver nanoplates. These nanoplates could exhibit an intensive surface plasmon resonance in the wavelength range of 700–1,400 nm in the UV–vis spectrum depending upon their shapes and sizes, which make them useful for optical applications, such as optical probes, ionic sensing, and biochemical sensors. A detailed analysis conducted in this study clearly shows that the reaction temperature can greatly influence reaction rate, and hence the particle characteristics. The findings would be useful for optimization of experimental parameters for shape-controlled synthesis of other metallic nanoparticles (e.g., Au, Cu, Pt, and Pd) with desirable functional properties.
Surface Fermi arcs (SFAs), the unique open Fermi-surfaces (FSs) discovered recently in topological Weyl semimetals (TWSs), are unlike closed FSs in conventional materials and can give rise to many ...exotic phenomena, such as anomalous SFA-mediated quantum oscillations, chiral magnetic effects, three-dimensional quantum Hall effect, non-local voltage generation and anomalous electromagnetic wave transmission. Here, by using in-situ surface decoration, we demonstrate successful manipulation of the shape, size and even the connections of SFAs in a model TWS, NbAs, and observe their evolution that leads to an unusual topological Lifshitz transition not caused by the change of the carrier concentration. The phase transition teleports the SFAs between different parts of the surface Brillouin zone. Despite the dramatic surface evolution, the existence of SFAs is robust and each SFA remains tied to a pair of Weyl points of opposite chirality, as dictated by the bulk topology.
The power spectrum of magnetic fluctuations in the solar wind at 1 AU displays a break between two power laws in the range of spacecraft‐frame frequencies 0.1 to 1 Hz. These frequencies correspond to ...spatial scales in the plasma frame near the proton gyroradius ρi and proton inertial length di. At 1 AU it is difficult to determine which of these is associated with the break, since di=ρi/β⊥i and the perpendicular ion plasma beta is typically β⊥i∼1. To address this, several exceptional intervals with β⊥i≪1 and β⊥i≫1 were investigated, during which these scales were well separated. It was found that for β⊥i≪1 the break occurs at di and for β⊥i≫1 at ρi, i.e., the larger of the two scales. Possible explanations for these results are discussed, including Alfvén wave dispersion, damping, and current sheets.
Key PointsIon‐scale spectral break measured in solar wind with very high and low betaBreak occurs at the larger of the ion gyroradius and ion inertial lengthResults compared to various theoretical expectations
In this work, a numerical study of the gas–solid flow in a gas cyclone is carried out by use of the combined discrete element method (DEM) and computational fluid dynamics (CFD) model where the ...motion of discrete particles phase is obtained by DEM which applies Newton’s equations of motion to every individual particle and the flow of continuum fluid by the traditional CFD which solves the Navier–Stokes equations at a computational cell scale. The model successfully captures the key flow features in a gas cyclone, such as the strands flow pattern of particles, and the decrease of pressure drop and tangential velocity after loading solids. The effect of solid loading ratio is studied and analysed in terms of gas and solid flow structures, and the particle–gas, particle–particle and particle–wall interaction forces. It is found that the gas pressure drop increases first and then decreases when solids are loaded. The reaction force of particles on gas flow is mainly in the tangential direction and directs mainly upward in the axial direction. The reaction force in the tangential direction will decelerate gas phase and the upward axial force will prevent gas phase from flowing downward in the near wall region. The intensive particle–wall collision regions mainly locate in the wall opposite to the cyclone inlet and the cone wall. Moreover, as the solid loading ratio increases, number of turns travelled by solids in a cyclone decreases especially in the apex region of the cyclone while the width of solid strands increases, the pressure drop and tangential velocity decrease, the high axial velocity region moves upwards, and the radial flow of gas phase is significantly dampened.
The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, ...therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3β independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/β-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.
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