Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Animal Research Regulation: Improving Decision-Making and Adopting a Transparent System to Address Concerns around Approval Rate of Experiments.

The use of nonhuman animals in biomedical research is regulated under stringent conditions, not only in response to societal attitudes towards animal experimentation but also because ethical responsibility in scientific research requires researchers and veterinarians to be more invested and aim to improve the welfare of animals used for experiments. Analyses of animal research oversight reveal the frequent approval of experiments, and the approval of some experiments has raised and continues to raise public concerns. Societal compliance is required for a consensus-based approach to animal research policy, prompting the need to have transparent discussions about oversight and the frequency of approvals. We discuss how frequent approval may be perceived and why it seems problematic from a societal perspective: the regulatory process exists to approve only legitimate experiments. Although some experiments remain unacceptable irrespective of their harm-benefit ratios, almost all experiments are approved. We explain some possible legitimate reasons for frequent approval and how the review process could be leading to the approval of illegitimate studies. To ensure transparency and improve public trust and understanding of oversight, we propose the adoption of a platform to inform society about how unethical experiments are screened out.

Perceptions of 3R implementation in European animal research: A systematic review, meta-analysis, and meta-synthesis of barriers and facilitators.

OBJECTIVES: The purpose of this systematic review was to examine how the scientific community in Europe that is involved with research with animals perceives and experiences the implementation of 3R (Replace, Reduce, Refine). METHODS: A systematic search of the literature published in the past ten years was performed in PubMed, Web of Science and Scopus. Publications were screened for eligibility using a priori inclusion criteria, and only empirical evidence (quantitative, qualitative, or mixed methodologies) was retained. Quantitative survey items were investigated by conducting a meta-analysis, and the qualitative data was summarized using an inductive meta-synthetic approach. Included publications were assessed using the Quality Assessment for Diverse Studies tool. RESULTS: 17 publications were included (eight quantitative, seven qualitative, two mixed-methods). The meta-analysis revealed that scientists are skeptical about achieving replacement, even if they believe that 3R improve the quality of experimental results. They are optimistic concerning the impact of 3R on research costs and innovation, and see education as highly valuable for the implementation of 3R. The meta-synthesis revealed four barriers (systemic dynamics, reification process, practical issues, insufficient knowledge) and four facilitators (efficient use of animals, caring for animals, regulatory uptake, supportive workplace environment). CONCLUSION: These findings show actionable levers at the local and systemic levels, and may inform regulators and institutions in their 3R policies. TRIAL REGISTRATION: The protocol was registered into the PROSPERO database under the number CRD42023395769.

Indoor cooking and cleaning as a source of outdoor air pollution in urban environments.

Indoor sources of air pollution, such as from cooking and cleaning, play a key role in indoor gas-phase chemistry. The focus of the impact of these activities on air quality tends to be indoors, with less attention given to the impact on air quality outside buildings. This study uses the INdoor CHEmical Model in Python (INCHEM-Py) and the Advanced Dispersion Modelling System (ADMS) to quantify the impact cooking and cleaning have on indoor and outdoor air quality for an idealised street of houses. INCHEM-Py has been developed to determine the concentrations of 106 indoor volatile organic compounds at the point they leave a building (defined as near-field concentrations). For a simulated 140 m long street with 10 equi-distant houses undertaking cooking and cleaning activities, the maximum downwind concentration of acetaldehyde increases from a background value of 0.1 ppb to 0.9 ppb post-cooking, whilst the maximum downwind chloroform concentrations increase from 1.2 to 6.2 ppt after cleaning. Although emissions to outdoors are higher when cooking and cleaning happen indoors, the contribution of these activities to total UK emissions of volatile organic compounds is low (less than 1%), and comprise about a quarter of those emitted from traffic across the UK. It is important to quantify these emissions, particularly as continued vehicle technology improvements lead to lower direct emissions outdoors, making indoor emissions relatively more important. Understanding how indoor pollution can affect outdoor environments, will allow better mitigation measures to be designed in the future that can take into account all sources of pollution that contribute to human exposure.

Case report: Organ donation after euthanasia for psychiatric suffering: some of the practical and ethical lessons Martijn taught us.

Euthanasia in psychiatric patients presents unique challenges, especially when combined with organ donation. In this article, the hurdles psychiatric patients might encounter after expressing their wish for organ donation after euthanasia, are discussed and illustrated by the case of Martijn, a 45-year-old psychiatric patient who altruistically donated his organs after euthanasia. Hospital and physician-related factors, including caution in determination of mental capacity, consideration of conflicting interests, and healthcare staff stress are discussed as impediments to organ donation after euthanasia (ODE) in psychiatric patients. The primary objective of this article is to raise awareness among psychiatrists regarding the fact that although the combination of euthanasia and organ donation is an uncommonly performed procedure, it is frequently requested by psychiatric patients. In conclusion, the article advocates for a nuanced approach, respecting patients' altruistic wishes while at the same time addressing challenges associated with ODE in psychiatric suffering. Where possible, and within the current medical, ethical and legal boundaries, the importance of facilitating organ donation without unnecessarily prolonging the suffering of competent psychiatric patients seeking euthanasia is emphasized. The topic calls, for example, for further qualitative research to understand the stakeholders' perspectives to determine the perceived possibilities on the one hand and boundaries on the other.

Point of care testing for hepatitis C in the priority settings of mental health, prisons and drug & alcohol facilities - the PROMPt Study.

BACKGROUND: A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care-testing (POCT) on testing rates, linkage to care, treatment and acceptability of testing in three priority settings in Australia. METHODS: Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service (MHS), and inpatient alcohol and other drug (AOD) unit-between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert® HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control. RESULTS: 1,549 participants received a HCV antibody test with 17% (264/1,549) receiving a positive result, of which 21% (55/264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by three-fold (RR:2.57 95% CI: 2.32, 2.85) for HCV antibody testing and four-fold (RR:1.62; 95% CI:1.31, 2.01) for RNA testing. Treatment uptake was higher during the POCT intervention (86%, 47/55; P=0.010) compared to the historical controls (61%, 27/44). CONCLUSIONS: This study demonstrated across three settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake linkage to care. The testing model was highly acceptable for most participants. CLINICAL TRIAL REGISTRATION: ACTRN-12621001578897.

Use of Expired Drugs: Patients Benefits versus Industry Interest.

The question of the use of expired medication is a constant debate of many years most especially in a difficult environment. In this research, a literature review and reported practice of some countries are used. Findings show that some medications, if properly stored, remain safe to use after the expiry date and this sometimes could be extended by many years. However, the pharmaceutical manufacturers have an interest in producing products with short shelf life. To dispose of expired ones is to generate a sale and therefore put the profit into the improvement and development of new products for the benefit of medicine. This paper emphasizes the benefit of use of some drugs after expiration and the interest for the pharmaceutical industry to dispose of expired drugs and to shorten their shelf life.

Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2.

Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring FGFR2 alterations, but the toxicity of these drugs frequently leads to dose reduction or interruption of treatment such that maximum efficacy cannot be achieved. The most common adverse effects are hyperphosphatemia caused by FGFR1 inhibition and diarrhea due to FGFR4 inhibition, as current therapies are not selective among the FGFRs. Designing selective inhibitors has proved difficult with conventional approaches because the orthosteric sites of FGFR family members are observed to be highly similar in X-ray structures. In this study, aided by analysis of protein dynamics, we designed a selective, covalent FGFR2 inhibitor. In a key initial step, analysis of long-timescale molecular dynamics simulations of the FGFR1 and FGFR2 kinase domains allowed us to identify differential motion in their P-loops, which are located adjacent to the orthosteric site. Using this insight, we were able to design orthosteric binders that selectively and covalently engage the P-loop of FGFR2. Our drug discovery efforts culminated in the development of lirafugratinib (RLY-4008), a covalent inhibitor of FGFR2 that shows substantial selectivity over FGFR1 (~250-fold) and FGFR4 (~5,000-fold) in vitro, causes tumor regression in multiple FGFR2-altered human xenograft models, and was recently demonstrated to be efficacious in the clinic at doses that do not induce clinically significant hyperphosphatemia or diarrhea.

Slaying the Swiss Unicorn of Animal Dignity.

In this article, we describe and analyse the Swiss legislation relating to animal dignity. We conclude that previous criticisms of the law do not go far enough: far from protecting animal dignity, the Swiss law not only undermines such dignity but itself serves as a means to ensure that animals can be used merely as a means, and not treated with respect. As such, the Swiss Animal Welfare Act is deeply unethical and undermines the constitutional requirement to treat animals with dignity.

Integrating ethics in AI development: a qualitative study.

BACKGROUND: While the theoretical benefits and harms of Artificial Intelligence (AI) have been widely discussed in academic literature, empirical evidence remains elusive regarding the practical ethical challenges of developing AI for healthcare. Bridging the gap between theory and practice is an essential step in understanding how to ethically align AI for healthcare. Therefore, this research examines the concerns and challenges perceived by experts in developing ethical AI that addresses the healthcare context and needs. METHODS: We conducted semi-structured interviews with 41 AI experts and analyzed the data using reflective thematic analysis. RESULTS: We developed three themes that expressed the considerations perceived by experts as essential for ensuring AI aligns with ethical practices within healthcare. The first theme explores the ethical significance of introducing AI with a clear and purposeful objective. The second theme focuses on how experts are concerned about the tension that exists between economic incentives and the importance of prioritizing the interests of doctors and patients. The third theme illustrates the need to develop context-sensitive AI for healthcare that is informed by its underlying theoretical foundations. CONCLUSIONS: The three themes collectively emphasized that beyond being innovative, AI must genuinely benefit healthcare and its stakeholders, meaning AI also aligns with intricate and context-specific healthcare practices. Our findings signal that instead of narrow product-specific AI guidance, ethical AI development may need a systemic, proactive perspective that includes the ethical considerations (objectives, actors, and context) and focuses on healthcare applications. Ethically developing AI involves a complex interplay between AI, ethics, healthcare, and multiple stakeholders.

Does green mean clean? Volatile organic emissions from regular versus green cleaning products.

Cleaning products emit a range of volatile organic compounds (VOCs), including some which are hazardous or can undergo chemical transformations to generate harmful secondary pollutants. In recent years, "green" cleaners have become increasingly popular, with an implicit assumption that these are better for our health and/or the environment. However, there is no strong evidence to suggest that they are better for indoor air quality compared to regular products. In this study, the VOC composition of 10 regular and 13 green cleaners was examined by headspace analysis. Monoterpenes were the most prevalent VOCs, with average total monoterpene concentrations of 8.6 and 25.0 mg L-1 for regular and green cleaners, respectively. Speciated monoterpene emissions were applied to a detailed chemical model to investigate the indoor air chemistry following a typical cleaning event. Green cleaners generally emitted more monoterpenes than regular cleaners, resulting in larger increases in harmful secondary pollutant concentrations following use, such as formaldehyde (up to 7%) and PAN species (up to 6%). However, emissions of the most reactive monoterpenes (α-terpinene, terpinolene and α-phellandrene), were observed more frequently from regular cleaners, resulting in a disproportionately large impact on the concentrations of radical species and secondary pollutants that were formed after cleaning occurred.

Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia.

PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor-positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor of PI3Kα. RLY-2608 inhibited tumor growth in PIK3CA-mutant xenograft models with minimal impact on insulin, a marker of dysregulated glucose homeostasis. RLY-2608 elicited objective tumor responses in two patients diagnosed with advanced hormone receptor-positive breast cancer with kinase or helical domain PIK3CA mutations, with no observed WT PI3Kα-related toxicities. SIGNIFICANCE: Treatments for PIK3CA-mutant cancers are limited by toxicities associated with the inhibition of WT PI3Kα. Molecular dynamics, cryo-electron microscopy, and DNA-encoded libraries were used to develop RLY-2608, a first-in-class inhibitor that demonstrates mutant selectivity in patients. This marks the advance of clinical mutant-selective inhibition that overcomes limitations of orthosteric PI3Kα inhibitors. See related commentary by Gong and Vanhaesebroeck, p. 204 . See related article by Varkaris et al., p. 227 . This article is featured in Selected Articles from This Issue, p. 201.

Long-term prediction of the effects of climate change on indoor climate and air quality.

Limiting the negative impact of climate change on nature and humans is one of the most pressing issues of the 21st century. Meanwhile, people in modern society spend most of the day indoors. It is therefore surprising that comparatively little attention has been paid to indoor human exposure in relation to climate change. Heat action plans have now been designed in many regions to protect people from thermal stress in their private homes and in public buildings. However, in order to be able to plan effectively for the future, reliable information is required about the long-term effects of climate change on indoor air quality and climate. The Indoor Air Quality Climate Change (IAQCC) model is an expediant tool for estimating the influence of climate change on indoor air quality. The model follows a holistic approach in which building physics, emissions, chemical reactions, mold growth and exposure are combined with the fundamental parameters of temperature and humidity. The features of the model have already been presented in an earlier publication, and it is now used for the expected climatic conditions in Central Europe, taking into account various shared socioeconomic pathway (SSP) scenarios up to the year 2100. For the test house examined in this study, the concentrations of pollutants in the indoor air will continue to rise. At the same time, the risk of mold growth also increases (the mold index rose from 0 to 4 in the worst case for very sensitive material). The biggest problem, however, is protection against heat and humidity. Massive structural improvements are needed here, including insulation, ventilation, and direct sun protection. Otherwise, the occupants will be exposed to increasing thermal discomfort, which can also lead to severe heat stress indoors.

Exploring the effect of region on diversity and composition of weed seedbanks in herbicide-resistant crop systems in the United States.

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Designed for a pandemic: Mitigating the risk of SARS-CoV-2 transmission through hospital design and infrastructure.

BACKGROUND: To describe the new Royal Adelaide Hospital (RAH) design and infrastructure features that helped mitigate the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission within the hospital during the pre-vaccination and pre-antiviral period. METHOD: The RAH infrastructure, design and initial pandemic response was assessed. A retrospective review of all confirmed or suspected coronavirus disease 2019 (COVID-19) patients admitted from 1 February 2020 to 30 May 2020 was also performed to assess risk of transmission. Outbreak response reports were reviewed to identify episodes of nosocomial COVID-19. RESULTS: Key infrastructure features include single-bed overnight rooms with dedicated bathrooms, creation of pandemic areas accessible only to pandemic staff, and sophisticated air-handling units with improved ventilation. A total of 264 COVID-19 related admission occurred, with 113 confirmed cases and 1579 total cumulative bed days. Despite a limited understanding of SARS-CoV-2 transmission, no vaccination or anti-viral therapy, global shortages of particulate filter respirators and restricted testing during this period, only one probable nosocomial COVID-19 case occurred in a healthcare worker, with no nosocomial cases involving patients. CONCLUSIONS: The RAH design and pandemic features complimented existing infection control interventions and was important in limiting nosocomial spread of SARS-CoV-2.

Understanding the patterns and health impact of indoor air pollutant exposures in Bradford, UK: a study protocol.

INTRODUCTION: Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes. METHODS AND ANALYSIS: 'Real Home Assessment' is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service.

Rudolph, the kids' ward reindeer: a scoping review of the effects of support animals on the well-being of healthcare staff.

BACKGROUND: Many systematic reviews identify support animals or animal assisted activity as a beneficial and standard practice in several medical disciplines for patients (children, adolescents, and adults) and residents in care homes. A variety of animals are used such as dogs, cats, ponies, horses, alpacas, reindeer, penguins, rabbits, and tarantulas. Our objective was to explore the evidence regarding effects of animal assisted activity on a further population of interest; namely, healthcare staff. METHODS: We asked the question "how do support animals in healthcare settings affect the well-being of healthcare staff?" As an addendum, we were also interested in what - possibly more unique - animals have visited healthcare settings at Christmas time in particular. We conducted a scoping literature review using PubMed and Web of Science (search as of 26 April 2023).  RESULTS: Twenty studies (in the USA, Australia, Europe; dogs: n = 19; cats: n = 1) since 2002 included: studies with biological measures (n = 3), longitudinal survey studies with analyses (n = 5), cross-sectional survey studies with analyses (n = 2), and cross-sectional survey studies with descriptive statistics (n = 10). Overall, animal assisted activities appear to be well-received by staff and there do not seem to be negative impacts on staff well-being. CONCLUSIONS: Relevant positive effects and avenues of research are identified. Our review suggests that, but not exactly how, animal assisted activity benefits staff. Study evidence is limited with most studies being cross-sectional, descriptive, having low participant numbers, and mostly only involving dogs. Nonetheless, the evidence is mostly positive. The potential of animal assisted activities impacting positively on staff well-being warrants systematic research. Gaps in hard-fact-evidence should not deter us - especially at the festive season - to encourage work with, and systematic research regarding, support animals that provide warmth, empathy, comfort, and more in healthcare settings.

Chemical data evaluation: general considerations and approaches for IUPAC projects and the chemistry community (IUPAC Technical Report).

The International Union of Pure and Applied Chemistry (IUPAC) has a long tradition of supporting the compilation of chemical data and their evaluation through direct projects, nomenclature and terminology work, and partnerships with international scientific bodies, government agencies and other organizations. The IUPAC Interdivisional Subcommittee on Critical Evaluation of Data (ISCED) has been established to provide guidance on issues related to the evaluation of chemical data. In this first report we define the general principles of the evaluation of scientific data and describe best practices and approaches to data evaluation in chemistry.

Update on the ethical, legal and technical challenges of translating xenotransplantation.

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation.

Playing Brains: The Ethical Challenges Posed by Silicon Sentience and Hybrid Intelligence in DishBrain.

The convergence of human and artificial intelligence is currently receiving considerable scholarly attention. Much debate about the resulting Hybrid Minds focuses on the integration of artificial intelligence into the human brain through intelligent brain-computer interfaces as they enter clinical use. In this contribution we discuss a complementary development: the integration of a functional in vitro network of human neurons into an in silico computing environment.To do so, we draw on a recent experiment reporting the creation of silico-biological intelligence as a case study (Kagan et al., 2022b). In this experiment, multielectrode arrays were plated with stem cell-derived human neurons, creating a system which the authors call DishBrain. By embedding the system into a virtual game-world, neural clusters were able to receive electrical input signals from the game-world and to respond appropriately with output signals from pre-assigned motor regions. Using this design, the authors demonstrate how the DishBrain self-organises and successfully learns to play the computer game 'Pong', exhibiting 'sentient' and intelligent behaviour in its virtual environment.The creation of such hybrid, silico-biological intelligence raises numerous ethical challenges. Following the neuroscientific framework embraced by the authors themselves, we discuss the arising ethical challenges in the context of Karl Friston's Free Energy Principle, focusing on the risk of creating synthetic phenomenology. Following the DishBrain's creator's neuroscientific assumptions, we highlight how DishBrain's design may risk bringing about artificial suffering and argue for a congruently cautious approach to such synthetic biological intelligence.