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Vaccitech, an Oxford University spinout company developing a universal flu vaccine has secured £20 million in Series A financing.
Endometriosis: A Review.
ImportanceEndometriosis is a chronic, estrogen-dependent, inflammatory disease defined by endometrial-like tissue (lesions) outside the uterine lining. It affects up to 10% of women worldwide, and 9 million women in the US, during reproductive years.ObservationsEndometriosis has varying clinical presentations; however, 90% of people with endometriosis report pelvic pain, including dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia, and 26% report infertility. Risk factors for endometriosis include younger age at menarche, shorter menstrual cycle length, lower body mass index, nulliparity, and congenital obstructive müllerian anomalies such as obstructed hemivagina. Although definitive diagnosis requires surgical visualization of lesions, a suspected clinical diagnosis can be made based on symptoms, supported by physical examination findings and imaging with transvaginal ultrasound and/or pelvic magnetic resonance imaging; normal physical examination and imaging do not exclude the diagnosis. The diagnosis is often delayed, averaging 5 to 12 years after onset of symptoms, with most women consulting 3 or more clinicians prior to diagnosis. Hormonal medications, such as combined oral contraceptives and progestin-only options, are first-line treatment and should be offered to symptomatic premenopausal women who do not currently desire pregnancy. In a network meta-analysis (n = 1680, 15 clinical trials), hormonal treatments including combined oral contraceptives, progestins, and gonadotropin-releasing hormone (GnRH) agonists led to clinically significant pain reduction compared with placebo, with mean differences ranging between 13.15 and 17.6 points (0-100 visual analog scale) with little difference in effectiveness among options. However, 11% to 19% of individuals with endometriosis have no pain reduction with hormonal medications and 25% to 34% experience recurrent pelvic pain within 12 months of discontinuing hormonal treatment. Surgical removal of lesions, usually with laparoscopy, should be considered if first-line hormonal therapies are ineffective or contraindicated. Second-line hormone therapies include GnRH agonists and antagonists, and third-line treatments include aromatase inhibitors. Hysterectomy with surgical removal of lesions may be considered when initial treatments are ineffective. However, approximately 25% of patients who undergo hysterectomy for endometriosis experience recurrent pelvic pain and 10% undergo additional surgery, such as lysis of adhesions, to treat pain.Conclusions and relevanceEndometriosis is a common cause of pelvic pain affecting approximately 10% of reproductive-age women. Hormonal suppression with combined estrogen-progestin contraceptives or progestins is first-line treatment for women who are not seeking immediate pregnancy. Surgical removal of endometriosis lesions may be performed if hormonal therapies are ineffective or contraindicated, and hysterectomy may be considered if medical treatments and surgical removal of lesions do not relieve symptoms.
Environmental impacts and emission profiles of volatile organic compounds from petroleum refineries.
This study evaluates the emissions of volatile organic compounds (VOCs) from petroleum refinery operations, focusing on quantifying the VOCs emission inventory, analyzing their spatial distribution, and assessing their environmental impacts. Emission measurements identified storage tanks as the primary source of VOCs, with pentane, cyclopentane, and cyclohexane being the dominant species. The total VOCs emissions were estimated at 1132.1 tons per year. Spatial dispersion modeling revealed that storage tanks contributed significantly to VOCs concentrations at receptor sites, accounting for 64.5-88.1% of the total VOCs emissions, followed by contributions from the wastewater treatment unit and marketing terminal. Ambient VOCs concentrations were then used to calculate secondary organic aerosol (SOA) levels, with toluene identified as the primary contributor to SOA formation in the surrounding environment. This study underscores the critical importance of targeting VOCs emissions, particularly from storage tanks, as a strategy to mitigate both VOCs and SOA concentrations. The findings highlight the potential for improved management and control strategies to reduce the environmental and public health risks associated with these emissions.
ESMO Precision Oncology Working Group recommendations on the structure and quality indicators for molecular tumour boards in clinical practice.
BackgroundWith an increased uptake of genomic profiling in clinical practice and the evolving complexity of diagnostic modalities, vast amounts of complex data need to be properly interpreted and integrated into an individualised care plan. To address these challenges, molecular tumour boards (MTBs) have been widely established. As of today, no international recommendations regulating the composition and workflows of MTBs have been defined.MethodsESMO's Precision Oncology Working Group (POWG) established an international expert panel in precision oncology and defined core areas of interest. After several consultations and through an expert consensus process, the group reached a consensus level for each recommendation.ResultsThe group defined five components in the MTB process that are critical to its function and clinical use: (i) the primary task of MTBs consists in providing genomic-informed clinical recommendations, particularly for cases exhibiting complex genomic alterations; (ii) to achieve this, MTBs should encompass interdisciplinary expertise, with key roles for oncologists with genomic expertise, pathologists with molecular training and clinical geneticists; (iii) MTBs' recommendations should be documented in a structured report that includes genomic-informed treatment strategies, management plans for potential tumour-detected germline alterations and guidance for additional genomic testing; (iv) structured follow-up processes should be implemented for monitoring the clinical effectiveness of MTBs recommendations and (v) finally, the panel proposed quality indicators for operating MTBs, including turnaround times for cases discussion and the proportion of cases for which actionable recommendations and clinical trial enrolments were successfully implemented.ConclusionsThese ESMO's POWG recommendations can serve as a guidance and help to define quality standards for MTBs to allow for harmonisation and to further expedite the integration of precision oncology into clinical practice.
Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study.
Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis tested 19,805 gene-disease links, revealing 165 TGCT-associated genes with a false discovery rate of less than 0.01. We prioritized 46 candidate genes by considering GWAS-inflated signals, correlations between neighboring genes, and evidence of colocalization. Among these, 23 genes overlap with 22 GWAS loci, with 7 being associations not previously implicated in TGCT risk. Additionally, 23 genes located within 21 loci are at least 1 Mb away from published GWAS index variants. The 46 prioritized genes display expression levels consistent with expected expression levels in human gonadal cell types and precursor tumor cells and significant enrichment in TGCTs. Additionally, immunohistochemistry revealed protein-level accumulation of two candidate genes, ARID3B and GINM1, in both precursor and tumor cells. These findings enhance our understanding of the genetic predisposition to TGCTs and underscore the importance of further functional investigations into these candidate genes.
Submicroscopic malaria in pregnancy and associated adverse pregnancy events: A case-cohort study of 4,352 women on the Thailand–Myanmar border
Background Malaria in pregnancy detected by microscopy is associated with maternal anaemia, reduced fetal growth, and preterm birth, but the effects of lower density (i.e., submicroscopic) malaria infections are poorly characterised. This analysis was undertaken to investigate associations between submicroscopic malaria at the first antenatal care (ANC) visit and these adverse pregnancy events on the Thailand–Myanmar border. Methods Blood samples taken from refugee and migrant pregnant women presenting for their first ANC visit were analysed retrospectively for malaria using ultrasensitive PCR (uPCR, limit of detection 22 parasites/mL). The relationships between submicroscopic malaria and subsequent microscopically detectable malaria, anaemia, birth weight, and preterm birth were evaluated using inverse probability weighting for stratified random sampling. Results First ANC visit samples from 4,352 asymptomatic women (median gestational age 16.5 weeks) attending between October 1st 2012 and December 31st 2015 were analysed. The weighted proportion of women with submicroscopic malaria infection was 4.6% (95% CI 3.9–5.6), comprising 59.8% (49.5–69.4) Plasmodium vivax, 6.5% (4.0–10.5) Plasmodium falciparum, 1.8% (0.9–3.6) mixed, and 31.9% (22.2–43.5) infections which could not be speciated. Submicroscopic parasitaemia at first ANC visit was associated with subsequent microscopically detected malaria (adjusted hazard ratio [HR] 12.9, 95% CI 8.8–18.8, p < 0.001) and lower birth weight (adjusted predicted mean difference −275 g, 95% CI −510 to −40, p = 0.022). There was no association with preterm birth. Submicroscopic P. falciparum mono-infection (adjusted HR 2.8, 95% CI 1.2–6.6, p = 0.023) and coinfection with P. falciparum and P. vivax (adjusted HR 10.3, 95% CI 2.6–40.4, p = 0.001) was associated with increased risk of maternal anaemia, but submicroscopic P. vivax mono-infection was not. That uPCR was conducted for only a part of the cohort due to cost constraints is a limitation. Conclusions In low transmission settings, uPCR identifies substantially more malaria infections at antenatal screening than conventional diagnostic methods. On the Thailand–Myanmar border, submicroscopic malaria at first antenatal consultation was associated with higher risks of microscopically diagnosed malaria later in pregnancy, anaemia, and reduced birth weight.
Shear-Dependent Platelet Aggregation by ChAdOx1 nCoV-19 Vaccine: A Novel Biophysical Mechanism for Arterial Thrombosis.
Rare thrombotic events associated with ChAdOx1 nCoV-19 (ChAdOx1) vaccination have raised concerns; however, the underlying mechanisms remain elusive. Here we report a novel biophysical mechanism by which ChAdOx1 directly interacts with platelets under arterial shear conditions, potentially contributing to post-vaccination arterial thrombosis. Using microfluidic post assays, we demonstrate that ChAdOx1 induces shear-dependent platelet aggregation, distinct from conventional von Willebrand factor-mediated adhesion. This interaction is mediated by platelet integrin αIIbβ3 and requires biomechanical activation, explaining the absence of significant binding under static conditions. Molecular dynamics simulations and docking studies reveal preferential binding of ChAdOx1's penton RGD motif to the activated conformation of αIIbβ3. Inhibiting integrin αIIbβ3 completely abolishes ChAdOx1-induced platelet aggregation, whereas blocking GPIb has minimal effect, confirming a mechanism that bypasses the conventional GPIb-dependent platelet adhesion pathway. Mutagenesis of the RGD motif to AAA eliminates platelet binding, verifying the specificity of this interaction. These findings provide a potential explanation for the association between ChAdOx1 vaccination and arterial thrombotic events, distinct from vaccine-induced immune thrombotic thrombocytopenia (VITT). Our results highlight the importance of considering biomechanical factors in vaccine-related thrombotic complications and suggest that shear-dependent integrin activation may be another determinant in the pathogenesis of these rare adverse events.
Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.
BackgroundPeople with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.MethodsThe PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions.FindingsPeople with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions.InterpretationPeople with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes.FundingUK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).
Pleural fluid proteomics from patients with pleural infection shows signatures of diverse neutrophilic responses: The Oxford Pleural Infection Endotyping Study (TORPIDS-2).
BackgroundPleural infection is a complex disease with poor clinical outcomes and increasing incidence worldwide, yet its biological endotypes remain unknown.MethodsWe analysed 80 pleural fluid samples from the PILOT study, a prospective study on pleural infection, using unlabelled mass spectrometry. A total of 449 proteins were retained after filtering. Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples and pathway analysis was performed to identify the biological processes. Protein signatures as identified by the pathway analysis were compared to microbiology as defined by 16S rRNA next generation sequencing. Spearman and exact Fischer's methods were used for correlation assessment.ResultsHigher neutrophil degranulation was correlated with increased glycolysis (OR=281, p<2.2E-16) and pentose phosphate activation (OR=371.45, p<2.2E-16). Samples dominated by Streptococcus pneumoniae exhibited higher neutrophil degranulation (OR=12.08, p=0.005), glycolysis (OR=11.4, p=0.006), and pentose phosphate activity (OR=12.82, p=0.004). On the other hand, samples dominated by anaerobes and Gram-negative bacteria exhibited lower neutrophil degranulation (OR=0.15, p=0.01, glycolysis (OR=0.14, p=0.01), and pentose phosphate activity (OR=0.07, p=0.001). Increased activity of the liver and retinoid X receptors (LXR-RXR) pathway was associated with lower risk of one-year mortality (OR=0.24, p=0.04).ConclusionsThese findings suggest that pleural infection patients exhibit diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation which are associated with microbiology. Therapeutic targeting of the LXR-RXR pathway with agonists is a possible treatment approach.
Understanding the primary healthcare context in rural South and Southeast Asia: a village profiling study
Abstract Background Understanding contextual factors is critical to the success of health service planning and implementation. However, few contextual data are available at the village level in rural South and Southeast Asia. This study addressed the gap by profiling representative villages across seven sites in Thailand (n=3), Cambodia, Laos, Myanmar and Bangladesh. Methods Key informant surveys supplemented by other information sources were used to collect data from 687 villages on four key indicators (literacy rate, and percentages of attended deliveries, fully immunised children and latrine coverage), as well as access to various services. Data were analysed descriptively. Results Sites varied considerably. Five were highly diverse ethno-culturally and linguistically, and all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. These were generally bypassed by severely ill patients for urban first-level referral hospitals and private sector facilities. While >75% of villages were near primary schools, educational attainment was generally low. Over 70% of villages at each site had mobile phone coverage and availability of electricity was high (≥65% at all sites bar Myanmar). Conclusion These results illustrate the similarities and differences of villages in this region that must be considered in public health research and policymaking.
History of scrub typhus in Indonesia.
Scrub typhus is a common but underrecognized cause of fever in the Asia-Pacific region. This review is the first to examine the history of scrub typhus in the context of notable historical events in Indonesia. Scrub typhus was first observed in 1902 and has since been documented through colonial and modern times. However, the available evidence is sparse. This lack of data is influenced by wider factors, including geopolitical climate and socio-economic factors. During the colonial era and World War II, research focused on economic and military interests. There were research gaps during the unstable period following independence in 1945. More research commenced only in the 1970s, mainly under the auspices of the Ministry of Health. Since 2000, there have been sporadic attempts to study scrub typhus on several major islands (Java, Sumatra, Sulawesi, Borneo, Bali). We found 51 relevant articles documenting the presence of the pathogen and its vectors, with only a single case confirmed with standard laboratory testing. This lack of data, combined with low awareness and diagnostic capacity, makes it difficult for policymakers to appreciate the impact of scrub typhus. Indonesia needs sustainable and continuous surveillance systems, infrastructure and research funding to ensure diseases of public health importance are not neglected.
Comparing HemoCue® and Quantitative Buffy Coat® and Coulter Counter-measured haemoglobin concentrations in African children with acute uncomplicated malaria: a Bland-Altman analysis.
BackgroundAnaemia is a deleterious consequence of malaria, and its accurate diagnosis is crucial for effective management. However, laboratory methods for measuring haemoglobin (Hb) concentration, like the Coulter Counter and the Quantitative Buffy Coat® (QBC®), are costly and not widely accessible in resource-limited settings. The point-of-care HemoCue® test is a cheaper alternative and suitable in rural areas. The study aimed to determine the level of agreement between Coulter Counter/QBC® vs. HemoCue®-measured Hb concentrations by Bland-Altman analysis.MethodsAs part of a randomized, placebo-controlled trial of single low-dose primaquine in Ugandan and Congolese children with acute uncomplicated Plasmodium falciparum malaria, Hb concentrations were measured on days 0, 3, 7, and 28 using Coulter Counter (Uganda, n = 1880 paired values), QBC® (DR Congo, n = 1984 paired values) and HemoCue® Hb-301™. The predefined clinically acceptable limits were set at ± 0.5 g/dL.ResultsThe Bland-Altman analysis showed that the HemoCue® minus Coulter Counter mean Hb difference was - 0.15 g/dL with lower and upper limits of agreement of - 3.68 g/dL and 3.39 g/dL, respectively. Corresponding HemoCue® minus QBC® values were - 0.23 g/dL, - 1.66 g/dL and 1.22 g/dL. Linear regression of Hb concentration differences vs. mean Hb concentrations showed negative correlations: r = - 0.43 and r = - 0.34 for HemoCue® vs. Coulter Counter and HemoCue® vs. QBC®, respectively.ConclusionsCompared to Coulter and QBC®, mean HemoCue® measured Hb concentrations were lower and, compared to the Coulter or QBC® methods, had an overall tendency to measure lower Hb concentrations with increasing Hb concentrations. Upper and lower limits of agreement were wider than the predefined clinically acceptable limits of ± 0.5 g/dL. HemoCue® should be used with caution in settings where decisions about blood transfusions are made.
Advancing artemisinin resistance monitoring using a high sensitivity ddPCR assay for Pfkelch13 mutation detection in Asia.
The spread of Pfkelch13 mutations in Southeast Asia threatens the effectiveness of artemisinin-based combination therapies (ACTs) for malaria. Previous studies revealed a high prevalence of key mutations, including C580Y, P574L, and R561H, emphasizing the need for the surveillance to combat drug resistance. This study, we developed a droplet digital PCR (ddPCR) assay for the rapid screening of common mutations including P441L, Y493H, P527H, G538V, R539T, I543T, R561H, P574L, C580Y, and A675V. The assay was designed to detect minor populations of mutant strain within multiple infection, offering high sensitivity and specificity using artificial mixtures of mutant and wild-type alleles. Field samples collected in Thailand during 2015-2020 and in 2023 (N = 130) were also analyzed to validate the assay in a real-world setting. The ddPCR assay demonstrated exceptional performance, with 100% sensitivity and 90% specificity. The R539T, R561H, and C580Y mutations were detected in clinical samples collected from several study sites in Thailand. Notably, the R561H mutation was detected in 100% of the P. falciparum isolates from Mae Hong Son, Thailand in 2023, underscoring the assay's utility in identifying critical mutations associated with drug resistance. Moreover, ddPCR can detect multiple parasite populations in clinical samples and can be used to analyze the ratios of wild-type and mutant alleles. These results validate the assay's ability to serve as a powerful tool for the early detection of minor allele frequencies, facilitating the timely implementation of interventions to curb the spread of ACT resistance. The ddPCR assays developed in this study provide a sensitive and specific method for detecting Pfkelch13 mutations, allowing the identification of minor parasite populations with artemisinin resistance. These assays enhance our ability to monitor and respond to malaria drug resistance, offering a crucial tool for early detection and contributing to global malaria elimination efforts.
Community responses to a novel house design: A qualitative study of "Star Homes" in Mtwara, southeastern Tanzania.
IntroductionTo evaluate the impact of a novel design "Star Home" on the incidence of malaria, respiratory tract infections and diarrheal diseases among children, randomly selected households in Mtwara, Tanzania were offered a free, new Star Home. Drawing on longitudinal qualitative research that accompanied the Star Homes study, this article describes the experiences of residents and the wider community of living with these buildings.MethodsA total of four rounds of face-to-face interviews were undertaken with residents of Star Homes (n = 37), control (wattle/daub) homes (n = 21), neighboring households n = 6), community members (n = 17) and community leaders (n = 6). The use of Star Homes was also observed over these four time periods between 2021 and 2023. Interviews were conducted in Swahili, transcribed, and translated into English for thematic analysis.ResultsStar Homes residents appreciated several aspects of the Star Homes, including overall comfort, access to water and electricity, and clean toilets. There were concerns about some design elements, such as poorly closing doors, stoves perceived as inefficient, and the façade, which was susceptible to rainwater ingress. The houses were not always used as intended by their developers, for example, residents were sleeping downstairs instead of upstairs because of cold floors or difficulties using the stairs. Star Homes residents described how the structures triggered praise but also envy from other community members.ConclusionsThe findings highlight the need for close attention to the use of novel design houses and careful sensitization around the potential benefits of dwellings to ensure that the intended health impacts of interventions are achieved.
Bringing the real world into the classroom through team-based live brief projects
Team-based project work in higher education provides opportunities to enhance collaborative learning, to strengthen students' academic skills in a work-related context, and to instil valuable transferable skills that relate to the modern workplace. This chapter explores existing literature on live briefs, their relevance to graduate employability, and how the involvement of external stakeholders can bring real-world experience into the classroom as part of a social constructivist approach to learning. Alongside an analysis of the different approaches documented in the literature, Live Brief examples are presented from a final-year undergraduate Computing and Software Engineering learning context within a higher education Institution based in England. The pedagogical underpinnings, benefits, ethical considerations, and challenges of live briefs are discussed along with other factors such as the value of student-staff-stakeholder partnerships, the importance of collaboration between academia and industry, potential applications of Generative Artificial Intelligence (GenAI), and the power of Social and Emotional Learning (SEL) through engagement with social issues.
Temporal correlations between RBD-ACE2 blocking and binding antibodies to SARS-CoV-2 variants in CoronaVac-vaccinated individuals and their persistence in COVID-19 patients.
Antibodies play a crucial role in protection against SARS-CoV-2. Understanding the correlation between binding and functional antibodies is essential to determine whether binding antibody levels can reliably predict neutralizing activity. We assessed antibody responses in 111 individuals vaccinated with the inactivated vaccine CoronaVac and 111 COVID-19 patients in Thailand. Plasma levels of ACE2-blocking antibodies targeting the receptor-binding domain (RBD) of SARS-Co-V2 variants were measured before vaccination and at 14 and 28 days after the second dose using a multiplex surrogate virus neutralization test. Anti-spike and anti-nucleocapsid antibodies were quantified by electrochemiluminescence immunoassay, and anti-RBD IgG by ELISA. After vaccination, blocking, anti-spike, and IgG antibody levels increased but declined rapidly within a month, whereas antibody levels in COVID-19 patients increased and persisted. Blocking and anti-spike antibody correlated at day 14 post-vaccination but not at day 28. In COVID-19 patients, correlations were moderate at day 14, and stronger at day 28. Correlations were weaker for Omicron subvariants than for the ancestral strain and non-Omicron variants. The weak correlation between blocking and anti-RBD IgG suggests binding antibodies might not predict neutralizing activity. These findings highlight the temporal nature of CoronaVac-induced immunity and the need for booster doses and variant-adapted vaccine.
Experiences, perceptions and ethical considerations of the malaria infection study in Thailand.
BackgroundThailand has made significant progress in malaria control efforts in the past decade, with a decline in the number of reported cases. However, due to cross-border movements over the past 5 years, reported malaria cases in Thailand have risen. The Malaria Infection Study in Thailand (MIST) involves deliberate infection of healthy volunteers with Plasmodium vivax malaria parasites, and the assessment of the efficacy of potential vaccine and drug candidates in order to understand acquired protection against malaria parasites.MethodsThis paper drew from ethics and social science qualitative study called MIST-ETHICS embedded within the MIST studies. MIST-ETHICS aimed to describe and understand the experiences, perceptions and ethical considerations of the MIST studies. Data were obtained from semi-structured interviews and a focus group discussion. A total of 46 participants participated in MIST-ETHICS .ResultsThree major themes emerged: experiences and perceptions of MIST, reasons for joining MIST, and ethical considerations. We found that although compensation was a motivation for participation, this was secondary to it being beneficial to self (health checks; link to health networks; building merit) and others (medical research contribution; altruism). Participants expressed varied opinions regarding the requirement of a university degree as one of the inclusion criteria for MIST.ConclusionsOur study revealed widespread concerns about long-term health effects and safety. Ethical considerations, including obtaining valid informed consent and ensuring participant inclusivitiy, were deem essential. Despite some debate regarding eligibility criteria, most participants agreed that the informed consent process was robust, accompanied by a strong sense of responsibility to contribute to the greater good. We emphasize the importance of continuously gathering participants' feedback for quality control, such as improving information materials to clarify the purpose of initial phases, their contributing to later phases, and the rationale behind each selection criterion.Trial registrationThis manuscript is part of the clinical trials registered under ClinicalTrials.gov IDs NCT04083508 (MIST1) registered on 5 Sep 2019 and NCT05071079 (MIST2) registered on 28 July 2021. However, the manuscript pertains to a qualitative study that does not require trial registration.