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This paper, based on the text of the Jakarta MS C. St. 125 published by Lukman Ali and M.S. Hutagalung (1996), shows by a comparative reading of selected samples of war-episodes in the hikayat, that, in spite of the countless differences between them, all ultimately tell one and the same underlying story. This story is in each war-episode retold in a process of constant variation within identity. This is done by combining “pre-fab” units that each form a slot in an already predetermined narrative structure. Each of these slots is filled with a selection of type-scenes, made from the particular string of type-scenes that is available for that particular slot. In order to shed light on the question where the hikayat’s author may have found the models and inspiration for its composition, the numerous intertextual echoes of Javanese and Malay literary genres and individual works audible in these war-episodes are also traced.

At the Worldwide Developers Conference in June 2023, Apple introduced the Vision Pro. The Apple Vision Pro (AVP) is a mixed reality headset; more specifically, it is a virtual reality device with an additional video see-through capability. The video see-through capability turns the AVP into an augmented reality (AR) device. The AR feature is enabled by streaming the real world via cameras on the (virtual reality) screens in front of the user’s eyes. This is, of course, not unique and is similar to other devices, such as the Varjo XR-3 (Varjo Technologies Oy). Nevertheless, the AVP has some interesting features, such as an inside-out screen that can show the headset wearer’s eyes to “outsiders,” and a button on the top, called the “digital crown,” that allows a seamless blend of digital content with the user’s physical space by turning it. In addition, it is untethered, except for the cable to the battery, which makes the headset more agile, compared to the Varjo XR-3. This could actually come closer to “The Ultimate Display,” which Ivan Sutherland had already sketched in 1965. After a great response from the media and social networks to the release, we were able to test and review the new AVP ourselves in March 2024. Including an expert survey with 13 of our colleagues after testing the AVP in our institute, this Viewpoint explores whether the AVP can overcome clinical challenges that AR especially still faces in the medical domain; we also go beyond this and discuss whether the AVP could support clinicians in essential tasks to allow them to spend more time with their patients.

Abstract The availability of computational hardware and developments in (medical) machine learning (MML) increases medical mixed realities’ (MMR) clinical usability. Medical instruments have played a vital role in surgery for ages. To further accelerate the implementation of MML and MMR, three-dimensional (3D) datasets of instruments should be publicly available. The proposed data collection consists of 103, 3D-scanned medical instruments from the clinical routine, scanned with structured light scanners. The collection consists, for example, of instruments, like retractors, forceps, and clamps. The collection can be augmented by generating likewise models using 3D software, resulting in an inflated dataset for analysis. The collection can be used for general instrument detection and tracking in operating room settings, or a freeform marker-less instrument registration for tool tracking in augmented reality. Furthermore, for medical simulation or training scenarios in virtual reality and medical diminishing reality in mixed reality. We hope to ease research in the field of MMR and MML, but also to motivate the release of a wider variety of needed surgical instrument datasets.

Abstract Background Triple-negative breast cancer (TNBC) is a subtype of breast cancer with limited treatment options and poor clinical prognosis. Inhibitors of transcriptional CDKs are currently under thorough investigation for application in the treatment of multiple cancer types, including breast cancer. These studies have raised interest in combining these inhibitors, including CDK12/13 inhibitor THZ531, with a variety of other anti-cancer agents. However, the full scope of these potential synergistic interactions of transcriptional CDK inhibitors with kinase inhibitors has not been systematically investigated. Moreover, the mechanisms behind these previously described synergistic interactions remain largely elusive. Methods Kinase inhibitor combination screenings were performed to identify kinase inhibitors that synergize with CDK7 inhibitor THZ1 and CDK12/13 inhibitor THZ531 in TNBC cell lines. CRISPR-Cas9 knockout screening and transcriptomic evaluation of resistant versus sensitive cell lines were performed to identify genes critical for THZ531 resistance. RNA sequencing analysis after treatment with individual and combined synergistic treatments was performed to gain further insights into the mechanism of this synergy. Kinase inhibitor screening in combination with visualization of ABCG2-substrate pheophorbide A was used to identify kinase inhibitors that inhibit ABCG2. Multiple transcriptional CDK inhibitors were evaluated to extend the significance of the found mechanism to other transcriptional CDK inhibitors. Results We show that a very high number of tyrosine kinase inhibitors synergize with the CDK12/13 inhibitor THZ531. Yet, we identified the multidrug transporter ABCG2 as key determinant of THZ531 resistance in TNBC cells. Mechanistically, we demonstrate that most synergistic kinase inhibitors block ABCG2 function, thereby sensitizing cells to transcriptional CDK inhibitors, including THZ531. Accordingly, these kinase inhibitors potentiate the effects of THZ531, disrupting gene expression and increasing intronic polyadenylation. Conclusion Overall, this study demonstrates the critical role of ABCG2 in limiting the efficacy of transcriptional CDK inhibitors and identifies multiple kinase inhibitors that disrupt ABCG2 transporter function and thereby synergize with these CDK inhibitors. These findings therefore further facilitate the development of new (combination) therapies targeting transcriptional CDKs and highlight the importance of evaluating the role of ABC transporters in synergistic drug–drug interactions in general.

Abstract Nature experiences, especially the visual aspects of nature, have been widely used to facilitate relaxation. Fueled by digital technology, simulated visual nature experiences have gained popularity in creating healing environments that induce relaxation. However, while easily applicable, not all nature-imitating visuals lead to relaxation. How to effectively design relaxing visual nature experiences remains largely unexplored. This paper investigates how different nature qualities facilitate relaxing visual experiences and the roles of two personal characteristics (mood and nature-relatedness) play. Through an online survey and interviews, we assessed 16 nature video clips, representing eight distinctive nature qualities, and compared perceived experiences while considering the influence of personal characteristics. The results indicate four types of visual qualities (engaging, instinctive, ambient, and derivative) underlying nature-induced relaxation, and show that nature relatedness influences the degree to which nature video clips elicit relaxation. We discuss design implications for creating personalized digital nature. [ABSTRACT FROM AUTHOR]

Defining immune correlates of disease severity is important to better understand the immunopathogenesis in COVID-19. Here we made use of a protein microarray platform to detect IgG- and IgA-reactive antibodies in sera and saliva respectively, and assess cross-reactivity between SARS-CoV-2 and endemic coronaviruses (eCoVs). IgG responses against the full protein of spike, but not the S1 subunit, were significantly higher in convalescent sera of patients with severe disease compared to mild disease and healthy controls. In addition, we detected reactivity of secretory IgA to eCoVs in saliva of patients with severe disease, not present in patients with moderate disease or seropositive healthy controls. These heterologous immune responses are in line with non-protective cross-reactivity, and support a potential role for immune imprinting in the pathogenesis of severe COVID-19.