Inhibition effect of a custom peptide on lung tumors

Cecropin B is a natural antimicrobial peptide and CB1a is a custom, engineered modification of it. In vitro, CB1a can kill lung cancer cells at concentrations that do not kill normal lung cells. Furthermore, in vitro, CB1a can disrupt cancer cells from adhering together to form tumor-like spheroids. Mice were xenografted with human lung cancer cells; CB1a could significantly inhibit the growth of tumors in this in vivo model. Docetaxel is a drug in present clinical use against lung cancers; it can have serious side effects because its toxicity is not sufficiently limited to cancer cells. In our studies in mice: CB1a is more toxic to cancer cells than docetaxel, but dramatically less toxic to healthy cells

Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Exploring and mitigating shortcomings in single-cell differential expression analysis with a new statistical paradigm

Background: Differential expression analysis is pivotal in single-cell transcriptomics for unraveling cell-type–specific responses to stimuli. While numerous methods are available to identify differentially expressed genes in single-cell data, recent evaluations of both single-cell–specific methods and methods adapted from bulk studies have revealed significant shortcomings in performance. In this paper, we dissect the four major challenges in single-cell differential expression analysis: excessive zeros, normalization, donor effects, and cumulative biases. These “curses” underscore the limitations and conceptual pitfalls in existing workflows. Results: To address the limitations of current single-cell differential expression analysis methods, we propose GLIMES, a statistical framework that leverages UMI counts and zero proportions within a generalized Poisson/Binomial mixed-effects model to account for batch effects and within-sample variation. We rigorously benchmarked GLIMES against six existing differential expression methods using three case studies and simulations across different experimental scenarios, including comparisons across cell types, tissue regions, and cell states. Our results demonstrate that GLIMES is more adaptable to diverse experimental designs in single-cell studies and effectively mitigates key shortcomings of current approaches, particularly those related to normalization procedures. By preserving biologically meaningful signals, GLIMES offers improved performance in detecting differentially expressed genes. Conclusions: By using absolute RNA expression rather than relative abundance, GLIMES improves sensitivity, reduces false discoveries, and enhances biological interpretability. This paradigm shift challenges existing workflows and highlights the need for careful consideration of normalization strategies, ultimately paving the way for more accurate and robust single-cell transcriptomic analyses.</p

Inventory Performance Related to Financial Performance? A Case Study in Manufacturing Sector

This study is to investigate the importance of inventory and the correlation to financial performance. The competitive marketplace has driven the supply chain environment complex and uncertain customer demand. The delivery speed is one of the significant factors to reach customer requirements in the manufacturing sector. The inability of delivering on time may cause the loss of business opportunities. Moreover, the inventory is a double edge sword to manufacturers, advantages and disadvantages appeared whether holding inventory or not. The purpose of this research is to investigate the inventory. First, to seek the correlation between inventory performance and the supply chain, and how the company enhances inventory performance by the supply chain activity. Second, to find the influence of financial performance if inventory performance improved. The findings shows that the internal company operation and the external supply chain collaboration assisted and improved inventory performance. Secondly, effective inventory management and a clear manufacturing strategy (such as purchasing timing, forecasting customer demand, the supply chain collaboration) are able to improve company’s financial performance, particularly on cash flow management