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Cell lines are essential tools to standardize and compare experimental findings in basic and translational cancer research. The current dogma states that cancer stem cells feature an increased tumor initiation capacity and are also chemoresistant. Here, we identified and comprehensively characterized three morphologically distinct cellular subtypes in the non–small cell lung cancer cell line A549 and challenge the current cancer stem cell dogma. Subtype-specific cellular morphology is maintained during short-term culturing, resulting in the formation of holoclonal, meroclonal, and paraclonal colonies. A549 holoclone cells were characterized by an epithelial and stem-like phenotype, paraclone cells featured a mesenchymal phenotype, whereas meroclone cells were phenotypically intermediate. Cell-surface marker expression of subpopulations changed over time, indicating an active epithelial-to-mesenchymal transition (EMT), in vitro and in vivo. EMT has been associated with the overexpression of the immunomodulators PD-L1 and PD-L2, which were 37- and 235-fold overexpressed in para- versus holoclone cells, respectively. We found that DNA methylation is involved in epigenetic regulation of marker expression. Holoclone cells were extremely sensitive to cisplatin and radiotherapy in vitro, whereas paraclone cells were highly resistant. However, inhibition of the receptor tyrosine kinase AXL, whose expression is associated with an EMT, specifically targeted the otherwise highly resistant paraclone cells. Xenograft tumor formation capacity was 24- and 269-fold higher in holo- than mero- and paraclone cells, respectively. Our results show that A549 subpopulations might serve as a unique system to explore the network of stemness, cellular plasticity, tumor initiation capacity, invasive and metastatic potential, and chemo/radiotherapy resistance.

This project aimed to share stories of six Indigenous mentees and their successes, struggles, and experiences in health science and in the Indigenous Mentorship Network Program. All participants were mentees within a mentorship network specific to their province. Mentees participated in semi-structured interviews about their experiences, which were transcribed and qualitatively coded using narrative analysis and Indigenous Storywork method. Stories were organized into motifs, or recurring narrative themes. Story vignettes based on each motif were created to express prominent experiences mentees faced. Our analysis derived motifs of struggle, overcoming, and traditional ways of learning. This project is intended to give Indigenous mentees a voice, expose areas where health education can support them, and share experiences of strength through adversity. Overall, this information can be used to educate, assist Indigenous mentorship programs, and support Indigenous mentees in health science.

Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

This project aimed to share stories of six Indigenous mentees and their successes, struggles, and experiences in health science and in the Indigenous Mentorship Network Program. All participants were mentees within a mentorship network specific to their province. Mentees participated in semi-structured interviews about their experiences, which were transcribed and qualitatively coded using narrative analysis and Indigenous Storywork method. Stories were organized into motifs, or recurring narrative themes. Story vignettes based on each motif were created to express prominent experiences mentees faced. Our analysis derived motifs of struggle, overcoming, and traditional ways of learning. This project is intended to give Indigenous mentees a voice, expose areas where health education can support them, and share experiences of strength through adversity. Overall, this information can be used to educate, assist Indigenous mentorship programs, and support Indigenous mentees in health science. [ABSTRACT FROM AUTHOR]

Adequate and efficient availability of medicines is necessary to ensure patients receive optimal care. However, inefficient drug stock management can result in various problems, such as waste of resources, lack of necessary drugs, or even excessive stock. This study aims to improve the efficiency of the drug stock management process by using KMeans Clustering and Hierarchical Clustering methods on drug stock data. The data used includes information on initial stock, purchase, incoming distribution, service, outgoing distribution, outgoing adjustment, and final stock. Clustering analysis was performed to identify patterns in the drug stock data, which was then validated using Silhouette Score. The results showed that Hierarchical Clustering was able to achieve a Silhouette Score of 0.976, while KMeans achieved a Silhouette Score of 0.954

In this study, we address the evolving threat of Maleficent Neural Networks, also known as “Evil” Neural Networks, malicious neural networks embedded with malware. Due to the absence of effective detection mechanisms, these malicious models remain undetected, posing significant challenges to the security of users and systems in the rapidly expanding field of Artificial Intelligence and Machine Learning. This research provides a comprehensive examination of Maleficent Neural Networks, and their detection, mitigation, and security issues, based on recent foundational studies. A discussion of ethical and legal concerns surrounding the deliberate infusion of malware into neural networks is also included, emphasising the need for collaborative efforts among experts in the fields of AI, machine learning, and cyber security. The study shows that this new threat possesses several risks, and the number of works on the topic we identified confirms that more research is needed in this direction. Moreover, we propose promising future directions, including the creation of advanced adversarial defence mechanisms and the development of new methods to detect malware within neural networks.

Abstract Given the importance of coastal upwelling systems to ocean productivity, fisheries, and biogeochemical cycles, their response to climate change is of great interest. However, there is no consensus on future productivity changes in these systems, which may be controlled by multiple drivers including wind‐driven and geostrophic transport, stratification, and source water properties. Here we use an ensemble of regional ocean projections and recently developed upwelling indices for the California Current System to disentangle these sometimes‐competing influences. Some changes are consistent among models (e.g., decreased mixed layer depth), while for others there is a lack of agreement even on the direction of future change (e.g., nitrate concentration in upwelled waters). Despite models' diverging projections of productivity changes, they agree that those changes are predominantly driven by subsurface nitrate concentrations, not by upwelling strength. Our results highlight the need for more attention to processes governing subsurface nutrient changes, not just upwelling strength.

BackgroundThe COVID-19 pandemic has forced many health care providers to make changes in their treatment, with telemedicine being expanded on a large scale. An earlier study investigated the acceptance of telephone calls but did not record satisfaction with treatment or patients’ preferences. This warranted a follow-up study to investigate acceptance, satisfaction, and preferences regarding telemedicine, comprising of phone consultations, among health care recipients. ObjectiveThe primary aim was to assess the acceptance and satisfaction of telemedicine during the subsequent months of 2021-2022, after the initial wave of the COVID-19 pandemic in Switzerland. Furthermore, we aimed to assess patients’ preferences and whether these differed in patients who had already experienced telemedicine in the past, as well as correlations between acceptance and satisfaction, pain intensity, general condition, perception of telemedicine, and catastrophizing. Finally, we aimed to investigate whether more governmental restrictions were correlated with higher acceptance. MethodsAn anonymous cross-sectional web-based survey was conducted between January 27, 2021, and February 4, 2022, enrolling patients undergoing outpatient pain therapy in a tertiary university clinic. We conducted a descriptive analysis of acceptance and satisfaction with telemedicine and investigated patients’ preferences. Further, we conducted a descriptive and correlational analysis of the COVID-19 stringency index. Spearman correlation analysis and a chi-square test for categorical data were used with Cramer V statistic to assess effect sizes. ResultsOur survey was completed by 60 patients. Telemedicine acceptance and satisfaction were high, with an average score of 7.6 (SD 3.3; on an 11-point Numeric Rating Scale from 0=not at all to 10=completely), and 8.8 (SD 1.8), respectively. Respondents generally preferred on-site consultations to telemedicine (n=35, 58% vs n=24, 40%). A subgroup analysis revealed that respondents who already had received phone consultation, showed a higher preference for telemedicine (n/N=21/42, 50% vs n/N=3/18, 17%; χ22 [N=60]=7.5, P=.02, Cramer V=0.354), as well as those who had been treated for more than 3 months (n/N=17/31, 55% vs n/N=7/29, 24%; χ22 [N=60]=6.5, P=.04, Cramer V=0.329). Acceptance of telemedicine showed a moderate positive correlation with satisfaction (rs{58}=0.41, P