Skin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to ...increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.
Static light scattering (SLS) combined with structure-based Monte Carlo (MC) simulations provide new insights into mechanisms behind anisotropic, attractive protein interactions. A nonmonotonic ...behavior of the osmotic second virial coefficient as a function of ionic strength is here shown to originate from a few charged amino acids forming an electrostatic attractive patch, highly directional and complementary. Together with Coulombic repulsion, this attractive patch results in two counteracting electrostatic contributions to the interaction free energy which, by operating over different length scales, is manifested in a subtle, salt-induced minimum in the second virial coefficient as observed in both experiment and simulations.
Many skin disorders, including cancer, have inflammatory components. The non-invasive detection of related biomarkers could therefore be highly valuable for both diagnosis and follow up on the effect ...of treatment. This study targets the extraction of tryptophan (Trp) and its metabolite kynurenine (Kyn), two compounds associated with several inflammatory skin disorders. We furthermore hypothesize that lipid-based bicontinuous cubic liquid crystals could be efficient extraction matrices. They comprise a large interfacial area separating interconnected polar and apolar domains, allowing them to accommodate solutes with various properties. We concluded, using the extensively studied GMO-water system as test-platform, that the hydrophilic Kyn and Trp favored the cubic phase over water and revealed a preference for locating at the lipid–water interface. The interfacial area per unit volume of the matrix, as well as the incorporation of ionic molecules at the lipid–water interface, can be used to optimize the extraction of solutes with specific physicochemical characteristics. We also observed that the cubic phases formed at rather extreme water activities (>0.9) and that wearing them resulted in efficient hydration and increased permeability of the skin. Evidently, bicontinuous cubic liquid crystals constitute a promising and versatile platform for non-invasive extraction of biomarkers through skin, as well as for transdermal drug delivery.
The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to ...identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.
Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. ...The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.
Cet article décrit la conception et la mise à l’essai d’un programme informatique de production semi-automatisée de cartes conceptuelles. Cette technique dérivée de l’extraction d’information a pour ...but de produire une représentation simple et signifiante du contenu d’un ou de plusieurs textes sous forme d’un schéma de connaissances. Le programme a été mis à l’essai à partir de deux corpus de textes choisis pour couvrir deux thèmes du Programme de formation de l’école québécoise de quatrième secondaire en science et technologie. Les résultats de l’étude sont très encourageants et montrent le potentiel d’une telle approche pour faciliter la construction d’une carte conceptuelle, une tâche qui est généralement réalisée par des humains. Les résultats suscitent également quelques réflexions quant aux modalités courantes d’élaboration et d’évaluation de cartes conceptuelles.
The COVID‐19 pandemic has accelerated the digitalization of assessment, creating new challenges for measurement professionals, including big data management, test security, and analyzing new validity ...evidence. In response to these challenges, Machine Learning (ML) emerges as an increasingly important skill in the toolbox of measurement professionals in this new era. However, most ML tutorials are technical and conceptual‐focused. Therefore, this tutorial aims to provide a practical introduction to ML in the context of educational measurement. We also supplement our tutorial with several examples of supervised and unsupervised ML techniques applied to marking a short‐answer question. Python codes are available on GitHub. In the end, common misconceptions about ML are discussed.
With the increased restrictions on physical distancing due to the COVID‐19 pandemic, remote proctoring has emerged as an alternative to traditional onsite proctoring to ensure the continuity of ...essential assessments, such as computer‐based medical licensing exams. Recent literature has highlighted the significant impact of different proctoring modalities on examinees’ test experience, including factors like response‐time data. However, the potential influence of these differences on test performance has remained unclear. One limitation in the current literature is the lack of a rigorous learning analytics framework to evaluate the comparability of computer‐based exams delivered using various proctoring settings. To address this gap, the current study aims to introduce a machine‐learning‐based framework that analyzes computer‐generated response‐time data to investigate the association between proctoring modalities in high‐stakes assessments. We demonstrated the effectiveness of this framework using empirical data collected from a large‐scale high‐stakes medical licensing exam conducted in Canada. By applying the machine‐learning‐based framework, we were able to extract examinee‐specific response‐time data for each proctoring modality and identify distinct time‐use patterns among examinees based on their proctoring modality.
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The aim of this study was to investigate the effect of various skin preservation protocols on in vitro drug permeation, epidermal-dermal drug distribution, and electrical impedance ...properties of skin membranes. Acyclovir (AC) and methyl salicylate (MS) were selected as model drugs due to their different physicochemical properties and skin metabolic profiles. In particular, AC is relatively hydrophilic (logP −1.8) and not expected to be affected by skin metabolism, while MS is relatively lipophilic (logP 2.5) and susceptible to metabolism, being a substrate for esterase residing in skin. Skin from pig ears was used and freshly excised into split-thickness membranes, which were divided and immediately stored at five different storage conditions: a) 4 °C overnight (fresh control), b) 4 °C for 4 days, c) and d) −20 °C for 6 weeks and one year, respectively, and e) −80 °C for 6 weeks. Based on the combined results, general trends are observed showing that fresh skin is associated with lower permeation of both model drugs and higher skin membrane electrical resistance, as compared to the other storage conditions. Interestingly, in the case of fresh skin, significantly lower amounts of MS are detected in the epidermis and dermis compartments, implying higher levels of ester hydrolysis of MS (i.e., higher esterase activity). In line with this, the concentration of salicylic acid (SA) extracted from the dermis is significantly higher for fresh skin, as compared to the other storage conditions. Nevertheless, for all storage conditions, substantial amounts of SA are detected in the receptor medium, as well as in the epidermis and dermis, implying that esterase activity is maintained to some extent in all cases. For AC, which is not expected to be affected by skin metabolism, freeze storage (protocols c-e) is observed to result in higher accumulation of AC in the epidermis, as compared to the case of fresh skin, while the AC concentration in dermis is unaffected. These observations can be rationalized primarily by the observed lower permeability of fresh skin towards this hydrophilic substance. Finally, a strong correlation between AC permeation and electrical skin resistance is shown for individual skin membranes irrespective of storage condition, while the corresponding correlation for MS is inferior. On the other hand, a strong correlation is shown for individual membranes between MS permeation and electrical skin capacitance, while a similar correlation for AC is lower. The observed correlations between drug permeability and electrical impedance open up for standardizing in vitro data for improved analysis and comparisons between permeability results obtained with skin stored at different conditions.
Newer electronic differential diagnosis supports (EDSs) are efficient and effective at improving diagnostic skill. Although these supports are encouraged in practice, they are prohibited in medical ...licensing examinations. The purpose of this study is to determine how using an EDS impacts examinees' results when answering clinical diagnosis questions.
The authors recruited 100 medical students from McMaster University (Hamilton, Ontario) to answer 40 clinical diagnosis questions in a simulated examination in 2021. Of these, 50 were first-year students and 50 were final-year students. Participants from each year of study were randomised into one of two groups. During the survey, half of the students had access to Isabel (an EDS) and half did not. Differences were explored using analysis of variance (ANOVA), and reliability estimates were compared for each group.
Test scores were higher for final-year versus first-year students (53 ± 13% versus 29 ± 10, p < 0.001) and higher with the use of EDS (44 ± 28% versus 36 ± 26%, p < 0.001). Students using the EDS took longer to complete the test (p < 0.001). Internal consistency reliability (Cronbach's alpha) increased with EDS use among final-year students but was reduced among first-year students, although the effect was not significant. A similar pattern was noted in item discrimination, which was significant.
EDS use during diagnostic licensing style questions was associated with modest improvements in performance, increased discrimination in senior students and increased testing time. Given that clinicians have access to EDS in routine clinical practice, allowing EDS use for diagnostic questions would maintain ecological validity of testing while preserving important psychometric test characteristics.
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