190 research outputs found
Triangular Pyramid
Triangular pyramid demonstrated a new concept of Clothing + (Clothing plus). Inspiration for this piece came from the triangular pyramid in geometric space. The triangular pyramid is one of the basic elements in geometry. This project combined various structures of clothing and triangular pyramid shapes to explore the relationship between clothing and geometry. In addition, the project was intended to enrich diverse forms of the clothing silhouette
Sugemalimab plus chemotherapy vs. chemotherapy for treatment of Chinese patients with esophageal squamous cell carcinoma: a cost effectiveness analysis to inform decision making
BackgroundThe GEMSTONE-304 trial established the clinical benefits of sugemalimab plus chemotherapy in advanced esophageal squamous-cell carcinoma (ESCC). This study evaluates the cost-effectiveness of this regimen versus chemotherapy alone as the first-line treatment for advanced ESCC patients from the perspective of China’s health system.MethodsWe established a partitioned survival model based on GEMSTONE-304 trial data, we simulated lifetime outcomes through three health states: progression-free survival, progressive disease, and death. Key parameters included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), analyzed with 5% discounting. Sensitivity analyses encompassed probabilistic, one-way, and scenario evaluations.ResultsThe sugemalimab combination yielded 0.336 incremental QALYs at 131,544.70/QALY). PD-L1 subgroup ICERs exhibited dose-dependent efficacy: 187,421.63/QALY (Combined Positive Score (CPS) < 1), 175,689.56 (1 ≤ CPS < 10), and 51,454.12/QALY under consideration of patient assistance program. None of the results demonstrated cost-effectiveness for this therapeutic regimen. Sensitivity analyses identified sugemalimab pricing as the dominant driver of ICER, while simultaneously validating the model’s internal and external validity. Price cap simulations determined that a minimum 91.20% price reduction is required to achieve cost-effectiveness.ConclusionCurrent pricing renders sugemalimab combination therapy economically unfavorable as first-line ESCC treatment in China. Strategic price adjustments could enhance cost-effectiveness potential
Development and Research on Incontinence Underwear for the Elderly
This study investigates the living conditions of elderly individuals with urinary incontinence and their usage of related products to assess their actual needs, including comfort, convenience, and affordability. Based on these findings, innovative design work was conducted, involving structural design, fabric preparation, and process selection. Ultimately, through product performance evaluation and refinement, the design requirements for comfort, convenience, and affordability were achieved. This research holds significant importance in addressing urinary incontinence issues among the elderly and can be applicable to individuals with restricted access to toilets or those engaged in prolonged activities. Furthermore, the study provides a valuable reference for designing and developing functional garments that cater to practical needs. With further production and market promotion, this research outcome is expected to yield greater value and impact on a larger scale.This paper was financially supported by the scientific research achievements of the National Experimental Teaching Demonstration Center for Fashion Design and Engineering (Dalian Polytechnic University) and the Fund Project of Science and Technology Project of Jiangxi Provincial Department of Education (GJJ202417)
Predicting In Vivo Anti-Hepatofibrotic Drug Efficacy Based on In Vitro High-Content Analysis
Background/Aims
Many anti-fibrotic drugs with high in vitro efficacies fail to produce significant effects in vivo. The aim of this work is to use a statistical approach to design a numerical predictor that correlates better with in vivo outcomes.
Methods
High-content analysis (HCA) was performed with 49 drugs on hepatic stellate cells (HSCs) LX-2 stained with 10 fibrotic markers. ~0.3 billion feature values from all cells in >150,000 images were quantified to reflect the drug effects. A systematic literature search on the in vivo effects of all 49 drugs on hepatofibrotic rats yields 28 papers with histological scores. The in vivo and in vitro datasets were used to compute a single efficacy predictor (Epredict).
Results
We used in vivo data from one context (CCl4 rats with drug treatments) to optimize the computation of Epredict. This optimized relationship was independently validated using in vivo data from two different contexts (treatment of DMN rats and prevention of CCl4 induction). A linear in vitro-in vivo correlation was consistently observed in all the three contexts. We used Epredict values to cluster drugs according to efficacy; and found that high-efficacy drugs tended to target proliferation, apoptosis and contractility of HSCs.
Conclusions
The Epredict statistic, based on a prioritized combination of in vitro features, provides a better correlation between in vitro and in vivo drug response than any of the traditional in vitro markers considered.Institute of Bioengineering and Nanotechnology (Singapore)Singapore. Biomedical Research CouncilSingapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technology Center (C-185-000-033-531)Janssen Cilag (R-185-000-182-592)Singapore-MIT Alliance Computational and Systems Biology Flagship Project (C-382-641-001-091)Mechanobiology Institute, Singapore (R-714-001-003-271
Free sulfurous acid (FSA) inhibition of biological thiosulfate reduction (BTR) in the sulfur cycle-driven wastewater treatment process
A sulfur cycle-based bioprocess for co-treatment of wet flue gas desulfurization (WFGD) wastes with freshwater sewage has been developed. In this process the removal of organic carbon is mainly associated with biological sulfate or sulfite reduction. Thiosulfate is a major intermediate during biological sulfate/sulfite reduction, and its reduction to sulfide is the rate-limiting step. In this study, the impacts of saline sulfite (the ionized form: HSO + SO ) and free sulfurous acid (FSA, the unionized form: HSO) sourced from WGFD wastes on the biological thiosulfate reduction (BTR) activities were thoroughly investigated. The BTR activity and sulfate/sulfite-reducing bacteria (SRB) populations in the thiosulfate-reducing up-flow anaerobic sludge bed (UASB) reactor decreased when the FSA was added to the UASB influent. Batch experiment results confirmed that FSA, instead of saline sulfite, was the true inhibitor of BTR. And BTR activities dropped by 50% as the FSA concentrations were increased from 8.0 × 10to 2.0 × 10mg HSO-S/L. From an engineering perspective, the findings of this study provide some hints on how to ensure effective thiosulfate accumulation in biological sulfate/sulfite reduction for the subsequent denitrification/denitritation. Such manipulation would result in higher nitrogen removal rates in this co-treatment process of WFGD wastes with municipal sewage
Comparison of proteomic landscape of extracellular vesicles in pleural effusions isolated by three strategies
Extracellular vesicles (EVs) derived from pleural effusion (PE) is emerging as disease biomarkers. However, the methods for isolation of EVs from PE (pEVs) were rarely studied. In our study, three methods for isolating pEVs of lung cancer patients were compared, including ultracentrifugation (UC), a combination of UC and size exclusion chromatography (UC-SEC) and a combination of UC and density gradient ultracentrifugation (UC-DGU). The subpopulation of pEVs was identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western blotting (WB) and nano-flow cytometry (nFCM). Additionally, the proteomic landscape of pEVs was analyzed by Label-free proteomics. The results showed that, compared with UC and UC-DGU, the UC-SEC method separated pEVs with the highest purity. In the proteomic analysis, on average, 1595 proteins were identified in the pEVs isolated by UC-SEC, much more than pEVs isolated by UC (1222) or UC-DGU (807). Furthermore, approximately 90% of identified proteins in each method were found in the EVs public database ExoCarta. Consistent with this, GO annotation indicated that the core proteins identified in each method were mainly enriched in “extracellular exosome.” Many of the top 100 proteins with high expression in each method were suggested as protein markers to validate the presence of EVs in the MISEV2018 guidelines. In addition, combined with lung tissue-specific proteins and vesicular membrane proteins, we screened out and validated several novel protein markers (CD11C, HLA DPA1 and HLA DRB1), which were enriched in pEVs rather than in plasma EVs. In conclusion, our study shows that the method of UC-SEC could significantly improve the purity of EVs and the performance of mass spectrometry-based proteomic profiling in analyzing pEVs. The exosomal proteins CD11C, HLA DPA1 and HLA DRB1 may act as potential markers of pEVs. The proteomic analysis of pEVs provides important information and new ideas for studying diseases complicated with PE
The impact of intraarterial, intravenous, and combined tirofiban on endovascular treatment for acute intracranial atherosclerotic occlusion
Background and purposeAdjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the effect of different administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD).MethodsPatients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0–1, 0–2, and 0–3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population.ResultsA total of 502 patients were included, 80 of which were in the IA-tirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0–5) vs. 1(0–4) vs. 1(0–4) vs. 3(0–5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45–1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78–2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64–1.64, P = 0.912). The adjusted OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27–0.98, P = 0.042) and 0.50 (95% CI, 0.26–0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18–0.94, P = 0.036), and the OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11–0.74, P = 0.011) and 0.25 (95% CI, 0.09–0.67, P = 0.006).ConclusionsIntra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful effect on patients undergoing EVT for ICAD-LVO.Clinical trial registrationhttp://www.clinicaltrials.gov, Unique identifier: NCT03370939
Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry
Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy
Triangular Pyramid
Triangular pyramid demonstrated a new concept of Clothing + (Clothing plus). Inspiration for this piece came from the triangular pyramid in geometric space. The triangular pyramid is one of the basic elements in geometry. This project combined various structures of clothing and triangular pyramid shapes to explore the relationship between clothing and geometry. In addition, the project was intended to enrich diverse forms of the clothing silhouette.</p
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