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Prokaryotic Argonaute (pAgo) nucleases with precise DNA cleavage activity show great potential for gene manipulation. Extensive biochemical studies have revealed that recognition of guides with different 5′ groups by Ago is important for biocatalysis. Here, we identified an Ago from the thermophilic Thermus parvatiensis (TpsAgo) and analyzed the regulatory effect of 5′-modified guides on TpsAgo cleavage activity. Recombinant TpsAgo cleaves single-stranded DNA and RNA targets at 65–90°C, which is mediated by a 5′ hydroxyl or phosphate DNA guide. Notably, TpsAgo can utilize various 5′-modified DNA guides for catalysis, including 5′-NH2C6, 5′-Biotin, 5′-FAM and 5′-SHC6 guides. Moreover, TpsAgo performs programmable cleavage of double-stranded DNA at temperatures over 80°C and strongly tolerates NaCl concentrations up to 3.2 M. These results provide insight into the catalytic performance of Agos by guide regulation, which may facilitate their biotechnological applications.

Combinational creativity, a form of creativity involving the blending of familiar ideas, is pivotal in design innovation. While most research focuses on how combinational creativity in design is achieved through blending elements, this study focuses on the computational interpretation, specifically identifying the ‘base’ and ‘additive’ components that constitute a creative design. To achieve this goal, the authors propose a heuristic algorithm integrating computer vision and natural language processing technologies, and implement multiple approaches based on both discriminative and generative artificial intelligence architectures. A comprehensive evaluation was conducted on a dataset created for studying combinational creativity. Among the implementations of the proposed algorithm, the most effective approach demonstrated a high accuracy in interpretation, achieving 87.5% for identifying ‘base’ and 80% for ‘additive’. We conduct a modular analysis and an ablation experiment to assess the performance of each part in our implementations. Additionally, the study includes an analysis of error cases and bottleneck issues, providing critical insights into the limitations and challenges inherent in the computational interpretation of creative designs. [ABSTRACT FROM AUTHOR]

Background: Both Wood's lamp and reflective confidential laser scanning microcopy are helpful for the diagnosis and treatment of vitiligo. However, there is few research that contains large samples and consistent observations. Aims: To analyze the characteristics of Wood's lamp images and reflectance confocal microscopy (RCM) images of vitiligo lesions and to evaluate their significance in vitiligo staging. Methods: We analyzed the characteristics of RCM images, Wood's lamp images, the vitiligo disease activity (VIDA) score, and clinical features to guide vitiligo staging and treatment. Results: The expert consensus based on the clinical features, VIDA score, Wood's lamp findings, and isomorphic response was consistent with the Wood's lamp findings (χ2 = 3.63, p > 0.05) and RCM findings (χ2 = 3.60, p > 0.05) in diagnosing vitiligo and assessing the disease stage. There was a correlation between the three lesion grades based on the Wood's lamp findings and the stage of vitiligo (p < 0.01). Lesions that appeared porcelain white under the Wood's lamp were in the slowly progressive stage; lesions that appeared gray‐white or trichromatic under the Wood's lamp were in the rapidly progressive stage; lesions with clear borders under the Wood's lamp needed further analysis by RCM for the stage to be determined; lesions with blurred borders under the Wood's lamp were in the rapidly progressive stage; lesions that were visible under the naked eye and under the Wood's lamp were in the rapidly progressive stage. Conclusion: The study demonstrates a reliable correlation between the findings of RCM (a sophisticated expensive tool) and Wood's lamp examination (a simple, readily available, inexpensive tool) in the assessment of the disease activity of vitiligo lesions. [ABSTRACT FROM AUTHOR]

Bio-inspired Design (BID) is a method that draws principles from biological systems to solve complex real-world problems. While diverse knowledge-based tools have served BID, the retrieval and reasoning capabilities of knowledge graphs have not been explored in BID. This study introduces a novel knowledge graph-based BID approach, exploiting the power of knowledge graphs to support BID. In the approach, a comprehensive ontology is defined and then applied to construct a BID-specific knowledge graph, enabling efficient representation of the diverse and rich biological knowledge. The knowledge graph supports BID by facilitating knowledge retrieval and reasoning. Retrieval in BID is accomplished by finding potential links between biological systems and relevant design applications. Reasoning in BID is supported by a link prediction model that follows the design process of mapping from biological systems to design applications. Two case studies are conducted to demonstrate the effectiveness of the approach. The first case shows that our approach outperforms other benchmarks in retrieving related biological knowledge, and the second case presents how the link prediction model aids in generating relevant and inspirational design ideas. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) level has been associated with various age‐related diseases and its pharmacological modulation emerges as a potential approach for aging intervention. But human NAD+ landscape exhibits large heterogeneity. The lack of rapid, low‐cost assays limits the establishment of whole‐blood NAD+ baseline and the development of personalized therapies, especially for those with poor responses towards conventional NAD+ supplementations. Here, we developed an automated NAD+ analyzer for the rapid measurement of NAD+ with 5 μL of capillary blood using recombinant bioluminescent sensor protein and automated optical reader. The minimal invasiveness of the assay allowed a frequent and decentralized mapping of real‐world NAD+ dynamics. We showed that aerobic sport and NMN supplementation increased whole‐blood NAD+ and that male on average has higher NAD+ than female before the age of 50. We further revealed the long‐term stability of human NAD+ baseline over 100 days and identified major real‐world NAD+‐modulating behaviors. [ABSTRACT FROM AUTHOR]

Herein we report on a patient with PLACK syndrome carrying compound heterozygous variants in I CAST i and provide a literature review. Dear Editor, PLACK syndrome (OMIM #616295) refers to an extremely rare autosomal-recessive genodermatosis characterized by a constellation of peeling skin, leuconychia, acral punctate keratoses, cheilitis and knuckle pads. [Extracted from the article]

Rituximab has proven effective for the treatment of steroid‐refractory bullous pemphigoid (BP), but there is controversy over the dosing protocol. We report three cases of refractory BP treated successfully with ultra‐low‐dose rituximab (100 mg weekly for 4 weeks). Our cases confirmed the efficacy and good follow‐up outcomes of this treatment strategy for refractory BP. The ultra‐low‐dose rituximab regimen (100 mg weekly for 4 weeks) may be a useful alternative therapy in patients with refractory BP. [ABSTRACT FROM AUTHOR]

In the field of content generation by machine, the state-of-the-art text-to-image model, DALL⋅E, has advanced and diverse capacities for the combinational image generation with specific textual prompts. The images generated by DALL⋅E seem to exhibit an appreciable level of combinational creativity close to that of humans in terms of visualizing a combinational idea. Although there are several common metrics which can be applied to assess the quality of the images generated by generative models, such as IS, FID, GIQA, and CLIP, it is unclear whether these metrics are equally applicable to assessing images containing combinational creativity. In this study, we collected the generated image data from machine (DALL⋅E) and human designers, respectively. The results of group ranking in the Consensual Assessment Technique (CAT) and the Turing Test (TT) were used as the benchmarks to assess the combinational creativity. Considering the metrics' mathematical principles and different starting points in evaluating image quality, we introduced coincident rate (CR) and average rank variation (ARV) which are two comparable spaces. An experiment to calculate the consistency of group ranking of each metric by comparing the benchmarks then was conducted. By comparing the consistency results of CR and ARV on group ranking, we summarized the applicability of the existing evaluation metrics in assessing generative images containing combinational creativity. In the four metrics, GIQA performed the closest consistency to the CAT and TT. It shows the potential as an automated assessment for images containing combinational creativity, which can be used to evaluate the images containing combinational creativity in the relevant task of design and engineering such as conceptual sketch, digital design image, and prototyping image. [ABSTRACT FROM AUTHOR]

Therefore, the mechanisms that promote interactions between metastatic tumour cells and activated tumour-associated lymphatic endothelium in primary tumours and draining lymph nodes should be investigated in more detail to prevent and treat EMPD. Extramammary Paget's disease (EMPD) is a rare tumour presenting with an erythematous spread in elderly patients, mainly in the genital region.[[1]] It is most common in Caucasian women, but in Asian populations, there is a male predominance.[[3]] Given the rarity of this disease, limited studies have reported the 5-year outcomes on the Chinese population; hence a comprehensive survival analysis on the Chinese mainland is still lacking. Additional prospective data are needed to clarify the characteristics of high-risk EMPD patients and to further identify better and more effective superior management approaches to recurrent and potential tumour metastasis. [Extracted from the article]

Data-driven design is a process to reuse data sources and provide valuable information to provoke creative ideas in the stages of design. However, existing semantic networks for design creativity are built on data sources restricted to technological and scientific information. Existing studies build the edges of a semantic network on statistical or semantic relationships, which are less likely to make full use of the benefits from both types of relationships and discover implicit knowledge for design creativity. Therefore, to overcome the gaps, we constructed WikiLink, a semantic network based on Wikipedia, which is an integrated source of general knowledge and specific knowledge, with broad coverage of disciplines. The weight in WikiLink fuses both the statistic and semantic weights between concepts instead of simply one type of weight, and four algorithms are developed for inspiring new ideas. Evaluation experiments are undertaken, and the results show that the network is characterised by high coverage of terms, relationships and disciplines, which demonstrates and supports the network's effectiveness and usefulness. A demonstration and case study results indicate that WikiLink can serve as an idea generation tool for creativity in conceptual design. The source code of WikiLink and the backend data are provided open-source for more users to explore and develop. [ABSTRACT FROM AUTHOR]

There are many facets to creativity, and the topic has a profound impact on society. Substantial and sustained study on creativity has been undertaken, and much is now known about the fundamentals and how creativity can be augmented. To draw these elements together, a framework was developed called the creativity diamond, formulated on the basis of reviews of prior work, as well as the consideration of 20 PhD studies on the topics of creativity, design, innovation, and product development. The framework embodies the principles that quantity of ideas breeds quality through selection, and that a range of creativity tools can provoke additional ideas to augment our innate creativity. The creativity diamond proposed is a tool consisting of a divergent phase associated with the development of many distinctive ideas and a convergent phase associated with the refinement of ideas. The creativity diamond framework can be used to prompt and help select which tool or approach to use in a creative environment for innovative tasks. The framework has now been used by many students and professionals in diverse contexts. [ABSTRACT FROM AUTHOR]

Reflectance confocal microscopy (RCM) enables good visualization of cutaneous structures, akin to an optical biopsy.[6] The examination takes a few minutes to be performed and is painless even when performed in sensitive areas such as the penis or vulva region. Vulvar lichen sclerosus (VLS) is not rare in paediatric dermatology.[1] Although histopathology is gold standard, the diagnosis of VLS is primarily based on clinical findings rather than histopathology,[2] which is may not always be practical or necessary in children.[3] There are no sufficient researches about using non-invasive tools in the diagnosis of VLS,[4] only few case report available on dermoscopy examination,[5] which might be less efficient as it studies only the surface. Notably, all VLS lesions were significantly characterized by the presence of unique highly reflective, quasi-circular large cells in the EDJ and superficial dermis at RCM. [Extracted from the article]