Patient-derived rectal cancer organoids—applications in basic and translational cancer research

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities

Patient and public involvement workshop to shape artificial intelligence-supported connected asthma self-management research

Digital interventions with artificial intelligence (AI) can potentially support people with asthma to reduce the risk of exacerbation. Engaging patients throughout the development process is essential to ensure usability of the intervention for the end-users. Using our Connected for Asthma (C4A) intervention as an exemplar, we explore how patient involvement can shape a digital intervention. Seven Patient and Public Involvement (PPI) colleagues from the Asthma UK Centre for Applied Research participated in four advisory workshops to discuss how they would prefer to use/interact with AI to support living with their asthma, the benefit and caveats to use the AI that incorporated asthma monitoring and indoor/outdoor environmental data. Discussion focussed on the three most wanted use cases identified in our previous studies. PPI colleagues wanted AI to support data collection, remind them about self-management tasks, teach them about asthma environmental triggers, identify risk, and empower them to confidently look after their asthma whilst emphasising that AI does not replace clinicians. The discussion informed the key components in the next C4A interventions, including the approach to interacting with AI, the technology features and the research topics. Attendees highlighted the importance of considering health inequities, the presentation of data, and concerns about data accuracy, data privacy, security and ownership. We have demonstrated how patient roles can shift from that of ‘user’ (the traditional ‘tester’ of a digital intervention), to a co-design partner who shapes the next iteration of the intervention. Technology innovators should seek practical and feasible strategies to involve PPI colleagues throughout the development cycle of a digital intervention; supporting researchers to explore the barriers, concerns, enablers and advantages of implementing digital healthcare.<br/

Mapping national information and communication technology (ICT) infrastructure to the requirements of potential digital health interventions in low- and middle-income countries

Background Digital health can support health care in low- and middle-income countries (LMICs) by overcoming problems of distance, poor infrastructure and the need to provide community practitioners with specialist support. We used five RESPIRE countries as exemplars (Bangladesh, India, Indonesia, Malaysia, Pakistan) to identify the digital health solutions that are valuable in their local setting, worked together with local clinicians and researchers to explore digital health policy, electricity/ICT infrastructure, and socio-cultural factors influencing users’ ability to access, adopt and utilise digital health. Methods We adopted the Joanna Briggs Institute’s scoping review protocol and followed the Cochrane Rapid Review method to accelerate the review process, using the Implementation and Operation of Mobile Health projects framework and The Extended Technology Acceptance Model of Mobile Telephony to categorise the results. We conducted the review in four stages: (1) establishing value, (2) identifying digital health policy, (3) searching for evidence of infrastructure, design, and end-user adoption, (4) local input to interpret relevance and adoption factors. We used open-source national/international statistics such as the World Health Organization, International Telecommunication Union, Groupe Speciale Mobile, and local news/articles/government statistics to scope the current status, and systematically searched five databases for locally relevant exemplars. Results We found 118 studies (2015-2021) and 114 supplementary online news articles and national statistics. Digital health policy was available in all countries, but scarce skilled labour, lack of legislation/interoperability support, and interrupted electricity and internet services were limitations. Older patients, women and those living in rural areas were least likely to have access to ICT infrastructure. Renewable energy has potential in enabling digital health care. Low usage mobile data and voice service packages are relatively affordable options for mHealth in the five countries. Conclusions Effective implementation of digital health technologies requires a supportive policy, stable electricity infrastructures, affordable mobile internet service, and good understanding of the socio-economic context in order to tailor the intervention such that it functional, accessible, feasible, user-friendly and trusted by the target users. We suggest a checklist of contextual factors that developers of digital health initiatives in LMICs should consider at an early stage in the development process

A game prototype for understanding the safety issues of a lifeboat launch

© 2018 The Author(s) Novel, advanced game techniques provide us with new possibilities to mimic a complicated training process, with the added benefit of enhanced safety. In this paper, we design and implement a 3D game with the support of virtual reality equipment which imitates the process of a lifeboat launch, involving both tractor manoeuvres and boat operations. It is a complex but vital process which can save lives at sea but also has many potential hazards. The primary objective of the game is to allow novices to better understand the sequence of the operations and manage the potential risks which may occur during the launch process. Additionally, the game has been promoted to the general public for educational purposes and to raise awareness of the safety issues involved. The key modules of the game are designed based on physical simulations to give the players enhanced plausible cognition and enjoyable interaction. We conducted two case studies for the two purposes of the games: one for training with volunteers without launching experience and the other for public awareness of the potential hazards with young children. The game is proven to be very promising for future professional training, and it serves the educational purpose of awareness of the safety issues for general public while being entertaining

Microwave studies of the fractional Josephson effect in HgTe-based Josephson junctions

The rise of topological phases of matter is strongly connected to their potential to host Majorana bound states, a powerful ingredient in the search for a robust, topologically protected, quantum information processing. In order to produce such states, a method of choice is to induce superconductivity in topological insulators. The engineering of the interplay between superconductivity and the electronic properties of a topological insulator is a challenging task and it is consequently very important to understand the physics of simple superconducting devices such as Josephson junctions, in which new topological properties are expected to emerge. In this article, we review recent experiments investigating topological superconductivity in topological insulators, using microwave excitation and detection techniques. More precisely, we have fabricated and studied topological Josephson junctions made of HgTe weak links in contact with two Al or Nb contacts. In such devices, we have observed two signatures of the fractional Josephson effect, which is expected to emerge from topologically-protected gapless Andreev bound states. We first recall the theoretical background on topological Josephson junctions, then move to the experimental observations. Then, we assess the topological origin of the observed features and conclude with an outlook towards more advanced microwave spectroscopy experiments, currently under development.Comment: Lectures given at the San Sebastian Topological Matter School 2017, published in "Topological Matter. Springer Series in Solid-State Sciences, vol 190. Springer

How might acupuncture work? A systematic review of physiologic rationales from clinical trials

BACKGROUND: Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. METHODS: The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. RESULTS: Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. CONCLUSION: Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions