In this work, we investigate the contact resistance between carbon nanotubes (CNTs) and different metal electrodes (In, Cr, Cu, Ni, W, and Bi) grown by two methods: floating catalyst chemical vapor ...deposition (FCCVD) and thin Fe metal chemical vapor deposition (CVD). The results demonstrate that CNTs grown by FCCVD have lower contact resistance with metal electrodes compared to those grown by thin Fe metal CVD. The study attributes this to the avoidance of metal-silicide formation between the silicon (Si) substrate and the metal catalyst film during the high-temperature growing process in FCCVD. Moreover, the research shows that the FCCVD method results in a higher CNT density grown in the through Si vias (TSVs) and lower contact resistance between metal electrodes and CNTs, moving toward the 3-D integrated circuits (3-DICs). Further, the use of metals with good wettability such as bismuth (Bi) as the metal electrode reduces contact resistance.
Background:
Synthetic cathinone abuse is a global health issue. Synthetic cathinones emerged in Taiwan in 2009, and their prevalence rapidly rose. They are usually made into “instant coffee packets,” ...and these so-called “toxic coffee packets” may also contain psychoactive drugs other than synthetic cathinones. Due to the diversity of the ingredients, clinical presentations can be complex.
Methods:
Retrospective analysis of emergency department (ED) patients who reported ingesting toxic coffee packets at three Chang-Gung Memorial Hospitals located in northern Taiwan between January, 2015 and December, 2019.
Results:
Sixty patients were included. Their mean age was 28.85 ± 9.24 years and 47(78.33%) were male. The most common presentations were palpitation, agitation, hallucination, and altered consciousness. Tachycardia and hypertension were common, while hyperthermia was observed in only three patients. Three patients (5%) developed rhabdomyolysis, and one underwent transient hemodialysis. Most patients were discharged from the ED, but 15(25%) were admitted, of whom nine (15%) were admitted to the intensive care unit (ICU), and one eventually died. Confirmation tests (mass-spectrometry-based analysis) were available in 10 patients; all reported positive for at least one type of synthetic cathinone. Polysubstance exposure was common. In multivariate logistic regression analyses, Glasgow coma scale ≤13 and the presence of seizure were associated with ICU admission.
Conclusion:
Patients who report ingesting toxic coffee packets are very likely to have been exposed to synthetic cathinones. Polysubstance exposure is common following ingestion. Cardiovascular and neurological symptoms are the main presentations, and severe complications such as rhabdomyolysis and life-threatening dysrhythmia can occur.
When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a ...follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities.
This study hypothesized that the “Delta CHA2DS2-VASc score,” which reflects the change in score between baseline and follow-up, would be more predictive of ischemic stroke compared with the baseline CHA2DS2-VASc score.
A total of 31,039 patients with AF who did not receive antiplatelet agents or oral anticoagulants, and who did not have comorbidities of the CHA2DS2-VASc score except for age and sex, were studied. The Delta CHA2DS2-VASc scores were defined as the differences between the baseline and follow-up CHA2DS2-VASc scores. During 171,956 person-years, 4,103 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were analyzed and compared.
The mean baseline CHA2DS2-VASc score was 1.29, which increased to 2.31 during the follow-up, with a mean Delta CHA2DS2-VASc score of 1.02. The CHA2DS2-VASc score remained unchanged in only 40.8% of patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta CHA2DS2-VASc score ≥1 compared with only 54.6% in patients without ischemic stroke, and 2,643 (64.4%) patients had ≥1 new-onset comorbidity, the most common being hypertension. The Delta CHA2DS2-VASc score was a significant predictor of ischemic stroke that performed better than baseline or follow-up CHA2DS2-VASc scores, as assessed by the C-index and the net reclassification index.
In this AF cohort, the authors demonstrated that the CHA2DS2-VASc score was not static, and that most patients with AF developed ≥1 new stroke risk factor before presentation with ischemic stroke. The Delta CHA2DS2-VASc score, reflecting the change in score between baseline and follow-up, was strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities.
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BackgroundDurable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains ...unclear.MethodsWe developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms.ResultsThe predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial (NCT02589496, N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features.ConclusionsCurrent study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy.
Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important in the era of personalized medicine. Liver-directed gene ...therapies present a unique challenge due to the complexity of the human liver. In this work, we describe the application of whole human liver explants in an ex situ normothermic perfusion system to evaluate a set of fourteen natural and bioengineered adeno-associated viral (AAV) vectors directly in human liver, in the presence and absence of neutralizing human sera. Under non-neutralizing conditions, the recently developed AAV variants, AAV-SYD12 and AAV-LK03, emerged as the most functional variants in terms of cellular uptake and transgene expression. However, when assessed in the presence of human plasma containing anti-AAV neutralizing antibodies (NAbs), vectors of human origin, specifically those derived from AAV2/AAV3b, were extensively neutralized, whereas AAV8- derived variants performed efficiently. This study demonstrates the potential of using normothermic liver perfusion as a model for early-stage testing of liver-focused gene therapies. The results offer preliminary insights that could help inform the development of more effective translational strategies.
Background and purpose: To investigate the relationships of diabetic neuropathy to all‐cause and diabetes‐related mortality in patients with type 2 diabetes after controlling for significant ...correlates.
Methods: We examined 326 patients diagnosed as diabetic polyneuropathy by nerve conduction study in Keelung city, Taiwan, in 2002 and followed them up to ascertain the cause and date of death until the end of 2006. The cause and date of death were recorded for the deceased patients. Information on significant correlates in association with diabetic polyneuropathy and all‐cause and diabetes‐related mortality was also collected.
Results: With median follow‐up time of 62.28 months, 44 patients with type 2 diabetes died. The cause of death related to diabetes accounted for 59% (n = 26) of the deceased. Univariate analysis shows that the presence of diabetic neuropathy confers higher risk for all‐cause mortality (hazard ratio HR = 4.88) and mortality from diabetes (HR = 6.58). The significant finding still persisted after adjustment for age, gender, blood pressure, smoking, history of cardiovascular/cerebrovascular disease, duration of diabetes, waist circumference, fasting plasma glucose, total cholesterol, hemoglobin, and creatinine (adjusted HR = 4.44 for all‐cause death and adjusted HR = 11.82 for diabetes‐related mortality, respectively).
Conclusions: Diabetic polyneuropathy was an independent predictor for all‐cause and diabetes‐related mortality. The presence of neuropathy together with other significant prognostic factors is informative to predict all‐cause death and death from diabetes‐related disease for patients diagnosed as type 2 diabetes.
Summary
Background
Both psoriasis and asthma are chronic immune‐mediated inflammatory diseases.
Objectives
To evaluate the risk of developing asthma in patients with psoriasis compared with controls.
...Methods
This cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Patients with psoriasis (n = 10 288) and matched comparison patients without psoriasis (n = 41 152) were evaluated. A Cox proportional hazard regression analysis was used to determine the risk of asthma in patients with and without psoriasis.
Results
The risk of asthma was 1·38‐fold higher 95% confidence interval (CI) 1·23–1·54 in the cohort with psoriasis than in the reference cohort, after adjusting for age, sex and comorbidities. The incidence of asthma in men and women with psoriasis exhibited nonsignificant differences. Among all patients aged > 50 years, psoriasis was associated with a higher risk of asthma compared with not having psoriasis adjusted hazard ratio (HR) 1·49; 95% CI 1·18–1·88 (in patients aged 50–64 years); adjusted HR 1·63; 95% CI 1·34–1·99 (in patients aged > 65 years).
Conclusions
Our results indicate that patients with psoriasis are associated with a increased risk of developing asthma.
What's already known about this topic?
Both psoriasis and asthma are chronic immune‐mediated inflammatory diseases.
Studies have shown that psoriasis is associated with systemic comorbidities.
Recent studies have defined psoriasis as a systemic chronic inflammatory disease.
What does this study add?
After adjusting for age, sex and comorbidities, the risk of asthma was 1·38‐fold higher in the cohort with psoriasis than in the reference cohort.
The incidence of asthma in male and female patients with psoriasis exhibited nonsignificant differences.
Among all patients aged > 50 years, patients with psoriasis were more likely to have higher risk of asthma compared with those without psoriasis.
Abstract This study aimed to investigate the particle size effect on bioactivity, cellular internalization and bioavailability of curcumin (CUR) nanosuspension (CUR-NS). CUR-NSs of different particle ...sizes were prepared by two different anti-solvent precipitation methods. CUR-NS with the smallest size showed similar in vitro anticancer activity and bioavailability to the CUR solution, whereas nanosuspensions of larger particle sizes displayed higher in vitro cellular internalization and cytotoxicity, as well as higher in vivo AUC and slower clearance rate after i.v. administration in rats. CUR solution and different sized CUR-NSs reached the highest concentrations in the lung, followed by liver and spleen while the lowest concentration was observed in the brain after i.v. administration in mice. Specifically, CUR-NS of 70 nm accumulated more in the brain, whereas CUR-NS of 200 nm accrued more in liver and spleen. CUR-NS of 20 nm displayed no significant biodistribution difference compared with CUR solution in all tissues.
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