Background and Aim
The anti‐interleukin‐23 antibody risankizumab is being investigated as a treatment for moderate‐to‐severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and ...safety of risankizumab therapy in Asian patients.
Methods
ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double‐blind, placebo‐controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double‐blind, placebo‐controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks.
Results
Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non‐Asian patients.
Conclusion
Consistent with non‐Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.
Significant advances have been made in the development of plasmonic devices in the past decade. Plasmonic nanolasers, which display interesting properties, have come to play an important role in ...biomedicine, chemical sensors, information technology, and optical integrated circuits. However, nanoscale plasmonic devices, particularly those operating in the ultraviolet regime, are extremely sensitive to the metal and interface quality. Thus, these factors have a significant bearing on the development of ultraviolet plasmonic devices. Here, by addressing these material-related issues, we demonstrate a low-threshold, high-characteristic-temperature metal-oxide-semiconductor ZnO nanolaser that operates at room temperature. The template for the ZnO nanowires consists of a flat single-crystalline Al film grown by molecular beam epitaxy and an ultrasmooth Al2O3 spacer layer synthesized by atomic layer deposition. By effectively reducing the surface plasmon scattering and metal intrinsic absorption losses, the high-quality metal film and the sharp interfaces formed between the layers boost the device performance. This work should pave the way for the use of ultraviolet plasmonic nanolasers and related devices in a wider range of applications.
Background & Aims The relationship between pyogenic liver abscess (PLA) and gastrointestinal (GI) cancer was first reported more than 20 years ago, yet little is known about this connection. We ...evaluated this association in a population-based, retrospective, cohort study. Methods Using Taiwan National Health Insurance claims data, we collected data on a cohort of 14,690 patients with PLA diagnosed from 2000 to 2007. A reference cohort of 58,760 persons without PLA (controls) was selected from the same database, frequency matched by age, sex, and index year. Both cohorts were followed up until the end of 2009, and incidences of GI cancer were calculated. Results The incidence of GI cancer was 4.30-fold higher among patients with PLA compared with controls (10.8 vs 2.51/1000 person-years). Site-specific analysis showed that the highest incidence of colorectal cancer was among patients with PLA and diabetes mellitus, followed by patients with PLA without diabetes and controls with diabetes (9.58, 5.76, and 1.49/10,000 person-years, respectively). The PLA cohort also had a high risk of small intestine cancer (adjusted hazard ratio aHR, 12.7; 95% confidence interval CI, 5.79–27.7) and biliary tract cancer (aHR, 9.56; 95% CI, 6.68–13.7). Their risk of pancreatic cancer (aHR, 2.51; 95% CI, 1.68–3.76) was also significant. However, patients with PLA did not have an increased risk of gastric cancer compared with controls. Conclusions In a population-based study, we found that the incidence of GI cancer is increased more than 4-fold among patients with PLA compared with controls. PLA might therefore be an indicator of GI cancer. Patients with PLA had the highest incidence of colorectal cancer, followed by cancers of the biliary tract, pancreas, and small intestine.
Abstract
The aims of the current study were to identify factors associated with sleep disturbance and Coronavirus disease-19 related psychological distress (CPD), and to develop a conceptual model to ...verify the mediating effect of CPD on the association between social impact and sleep disturbance. This study recruited patients with schizophrenia. Factors associated with the level of sleep disturbance and CPD were identified using univariate linear regression, and further selected into a stepwise multivariate linear regression model. Using structural equation modeling, a mediation model was developed to test the mediating effect of CPD on the association between social impact and sleep disturbance. After estimating with the stepwise and bootstrap regression, higher levels of CPD were associated with higher levels of social anxiety and subjects without a regular diet. Sleep disturbance was associated with a higher level of social anxiety, a history of psychological trauma, chronic disease, and those who did not smoke. The final model confirmed the mediating effects of CPD; whereas, the direct effect from social impact to sleep disturbance did not reach statistical significance. The current study manifests the crucial role of CPD on the association between social impact and sleep disturbance, and timely intervention for CPD is warranted.
Human caspase‐4 and its mouse homolog caspase‐11 are receptors for cytoplasmic lipopolysaccharide. Activation of the caspase‐4/11‐dependent NLRP3 inflammasome is required for innate defense and ...endotoxic shock, but how caspase‐4/11 is modulated remains unclear. Here, we show that mice lacking the oxidative stress sensor glutathione peroxidase 8 (GPx8) are more susceptible to colitis and endotoxic shock, and exhibit reduced richness and diversity of the gut microbiome. C57BL/6 mice that underwent adoptive cell transfer of GPx8‐deficient macrophages displayed a similar phenotype of enhanced colitis, indicating a critical role of GPx8 in macrophages. GPx8 binds covalently to caspase‐4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase‐4 and thus restrains caspase‐4/11 activation, while GPx8 deficiency leads to caspase‐4/11‐induced inflammation during colitis and septic shock. Inhibition of caspase‐4/11 activation with small molecules reduces the severity of colitis in GPx8‐deficient mice. Notably, colonic tissues from patients with ulcerative colitis display low levels of Gpx8 and high caspase‐4 expression. In conclusion, these results suggest that GPx8 protects against colitis by negatively regulating caspase‐4/11 activity.
Synopsis
Human caspase‐4 and its mouse homolog caspase‐11 are required for innate immune responses. This study highlights how GPx8, an oxidative stress sensor, protects against colitis by negatively regulating caspase‐4/11 activity.
Mice lacking GPx8 are more susceptible to colitis and endotoxic shock, and exhibit reduced richness and diversity of the gut microbiome.
GPx8 binds covalently to caspase‐4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase‐4, thus restrains caspase‐4/11 activation.
Inhibition of caspase‐4/11 activation with a caspase‐4/11 inhibitor, VX‐765, reduces colitis severity in GPx8‐deficient mice.
Colonic tissues from patients with ulcerative colitis display low levels of Gpx8 and high caspase‐4 expression.
Using a caspase‐4/11 inhibitor alone or in combination with an antioxidant may be a promising therapeutic option for IBD patients.
Human caspase‐4 and its mouse homolog caspase‐11 are required for innate immune responses. This study highlights how GPx8, an oxidative stress sensor, protects against colitis by negatively regulating caspase‐4/11 activity.
Without demosaicing processing, this paper first proposes a new approach to extract more accurate gradient/edge information on mosaic images directly. Next, based on spectral-spatial correlation, a ...novel adaptive heterogeneity-projection with proper mask size for each pixel is presented. Combining the extracted gradient/edge information and the adaptive heterogeneity-projection values, a new edge-sensing demosaicing algorithm is presented. Based on 24 popular testing images, experimental results demonstrated that our proposed high-quality demosaicing algorithm has the best image quality performance when compared with several recently published algorithms.
In this study, the negative bias temperature instability (NBTI) under mechanical strain conditions of low-temperature polycrystalline silicon thin-film transistors (LTPS TFTs) with a stress-release ...structure was investigated. With both electrical and mechanical stresses simultaneously applied, more significant degradation behaviors will be observed in standard TFT devices because mechanical stress makes it easier to generate strain in Si-H bonds, thus benefiting the process of electrochemical reaction. By employing a stress-release shape in the poly channel, mechanical stress, which mainly accumulates at the width edge of the poly-Si/SiO 2 interface, is moved away from the main channel; thus, fewer strained Si-H bonds can participate in the electrochemical reaction compared to the standard structure. Therefore, the degradation of devices under strained NBTI is effectively mitigated, such that the reliability of the devices is enhanced. These observations were obtained using electrical characteristics and extraction of the trap state distribution.
In this work, the supercritical oxygen treatment is proposed to passivate the defects of enhancement-mode p-GaN high-electron mobility transistors. After the treatment, the treated device gets ...enhanced in ON-state current and transconductance without changing the threshold voltage. Thus, the supercritical oxygen may not affect Mg doping concentration of the p-GaN layer, degrading the p-GaN layer after the treatment. The statistical analysis indicates uniformity of devices is improved after the treatment. The gate lag and pulsed <inline-formula> <tex-math notation="LaTeX">\text{I}_{\text {D}} </tex-math></inline-formula>-<inline-formula> <tex-math notation="LaTeX">\text{V}_{\text {D}} </tex-math></inline-formula> measurements are proposed to examine the interface between the passivation layer and the AlGaN layer. The few trapped electrons in defects exhibit the suppression of the charge trapping effect. Based on these results mentioned above, the physical model is proposed to explain the phenomenon. The pristine passivation layer has a number of dangling bonds which capture the electrons and lead to the charge trapping effect. The supercritical oxygen permeates into material matrix, repairing the dangling bonds. Therefore, the technique exhibits potential for power device improvement, enabling effective practical application in the future.
Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed ...to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.
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