Abstract
Background
Prolonged fever is associated with adverse outcomes in dengue viral infection. Similar fever patterns are observed in COVID-19 with unclear significance.
Methods
We conducted a ...hospital-based case–control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). Fever was defined as a temperature of ≥38.0°C. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality.
Results
A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. Those with prolonged fever had a median duration of fever (interquartile range IQR) of 10 (9–11) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (8–12) days for those with saddleback fever. Both prolonged (27.8% vs 0.9%; P < .01) and saddleback fever (14.3% vs 0.9%; P = .03) were associated with hypoxia compared with controls. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). Patients with prolonged fever had higher induced protein–10 and lower interleukin-1α levels compared with those with saddleback fever at the early acute phase of disease.
Conclusions
Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Patients with saddleback fever appeared to have good outcomes regardless of the fever.
The evolution of stress during damage initiation and accumulation in a two-phase alloy consisting of a ductile copper (Cu) matrix with a randomly dispersed brittle tungsten (W) phase was studied ...using multiple non-destructive experimental probes. Neutron diffraction measurements were performed to examine the macroscopic strain partitioning between the two phases during a uniaxial tension test. The same material was then examined with high-energy x-ray diffraction microscopy (HEDM) and micro-computed tomography (μ-CT) measurements to monitor micromechanical field evolution. The neutron diffraction data indicated a redistribution of load between the Cu and W phases as deformation proceeds. Therefore, using HEDM to monitor individual grain micromechanical behavior, an increase followed by decrease in hydrostatic stress and a similar stress triaxiality behavior were found to occur in a subset of W grains. These same W grains were found to be in close proximity to voids observed via tomography at later stages of deformation. From these observations, we conclude that high stress triaxiality development in the W particles leads to decohesion of the interface between the Cu and W phases. The debonded regions eventually grew and coalesced with neighboring voids leading to material failure.
Dendritic cells (DC) are required for priming antigen‐specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, ...inappropriate priming of auto‐reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti‐inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen‐specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases.
IKKα kinase has anti‐inflammatory activity. Here, IKKα is shown to be required in dendritic cells for T‐cell priming and acquired immunity to Listeria monocytogenes. IKKα thus inhibits the innate and activates the adaptive immune systems.
This paper presents an overview on optimizing interoperability between different applications for enhanced return-on-investment through utilization of business intelligence in conjunction with ...prognostics and health management methodology. Such implementation is particularly suitable for deployment in mass-produced vehicle onboard diagnostics system.
Background
This study utilized the imaging data of primary liver cancer (PLC) treated with floxuridine (FUDR) and bevacizumab to test the hypothesis that dynamic contrast-enhanced magnetic resonance ...imaging (DCE-MRI) parameters correlate with tissue hypoxia markers and treatment outcome.
Methods
Seventeen patients with PLC were treated with hepatic artery infusional (HAI) FUDR for 14 days followed by systemic bevacizumab therapy. DCE-MRI images were obtained at baseline and after HAI FUDR and bevacizumab therapy. The parameters (K
trans
, AUC) pertaining to perfusion and vascular permeability of the tumor and adjacent liver parenchyma were measured with DCE-MRI. Tissue obtained at baseline was stained for hypoxia markers (anti-hypoxia inducible factor-1α, anti-carbonic anhydrase IX, and vascular endothelial growth factor). Changes in DCE-MRI parameters were correlated with tissue hypoxia and time to progression (TTP).
Results
The median TTP was 8.8 months. Significant decreases in AUC90 (
P
= 0.004), AUC180 (
P
= 0.004), and K
trans
(
P
= 0.05) were noted in tumors after bevacizumab but not in nontumor areas. TTP correlated inversely with changes in AUC90 and AUC180 after bevacizumab (
P
= 0.002 and
P
= 0.0001). Reductions in tumor perfusion (AUC90 and AUC180) were greater in tumors expressing anti-hypoxia inducible factor-1α (
P
= 0.02 and 0.03), vascular endothelial growth factor (
P
= 0.01 and
P
= 0.01), and anti-carbonic anhydrase IX (
P
= 0.009 and
P
= 0.009).
Conclusions
In patients with PLC, bevacizumab induces a reduction in tumor perfusion measured by DCE-MRI. These changes correlate with TTP and tissue markers of tumor hypoxia.
There is strong interest in the valorization of lignin to produce valuable products; however, its structural complexity has been a conversion bottleneck. Chemical pretreatment liberates ...lignin-derived soluble fractions that may be upgraded by bioconversion. Here, cholinium ionic liquid pretreatment of sorghum produced soluble, aromatic-rich fractions that were converted by Pseudomonas putida (P. putida), a promising host for aromatic bioconversion. Growth studies and mutational analysis demonstrated that P. putida growth on these fractions was dependent on aromatic monomers but unknown factors also contributed. Proteomic and metabolomic analyses indicated that these unknown factors were amino acids and residual ionic liquid; the oligomeric aromatic fraction derived from lignin was not converted. A cholinium catabolic pathway was identified, and the deletion of the pathway stopped the ability of P. putida to grow on cholinium ionic liquid. This work demonstrates that aromatic-rich fractions obtained through pretreatment contain multiple substrates; conversion strategies should account for this complexity.
We recently reported that Semaphorin 4D (Sema4D) and its receptors are expressed on the platelet surface and showed that Sema4D(−/−) mice have a selective defect in collagen-induced platelet ...aggregation and an impaired vascular injury response. Here we investigated the mechanisms involved, tested the role of platelet-platelet contacts in Sema4D-mediated events, and examined the relationship between Sema4D-dependent signaling and integrin αIIbβ3 outside-in signaling. The results show that spleen tyrosine kinase (Syk) activation, an early step in collagen signaling via the glycoprotein VI (GPVI)/FcRγ complex, is greatly reduced in Sema4D(−/−) platelets and can be restored by adding soluble Sema4D. Earlier events, including FcRγ phosphorylation, occur normally; later events are impaired. In contrast, when engagement of αIIbβ3 was blocked, Sema4D(−/−) and control platelets were indistinguishable in assays of Syk activation, adhesion, spreading on collagen, and activation of αIIbβ3. Finally, we found that, unlike the Sema4D knockout, αIIbβ3 blockade inhibited FcRγ phosphorylation and that stimulating aggregation with Mn2+ failed to normalize Syk activation in the absence of Sema4D. Collectively, these results show that αIIbβ3 and Sema4D jointly promote collagen responses by amplifying Syk activation, partly by forming integrin-mediated contacts that enable the binding of Sema4D to its receptors and partly through integrin outside-in signaling. These 2 processes are interdependent, but distinguishable.
A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation ...it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.
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