Phenotyping of Macrophages in Human Immune System Mice.

Human immune system mice, also referred to as humanized mice, are a major research tool for the in vivo study of human immune system function. Upon reconstitution with human hematopoietic stem cells, all major human leukocyte populations develop in immunodeficient mice and can be detected in peripheral blood as well as in lymphatic and nonlymphatic tissue. This includes human macrophages that are intrinsically difficult to study from humans due to their organ-resident nature. In the following chapter, we provide a detailed protocol for generation of human immune system mice. We suggest that these mice are a suitable model to study human macrophage function in vivo.

Experts' assessments of migration scenarios between the Middle East & North Africa and Europe.

We describe data collected among 138 migration experts about the repercussions of scenarios of social change on migration between the Middle East & North Africa and Europe, during the period 2021-2030. Scenarios include changes in the cultural, demographic, economic, and political determinants of migration in sending and receiving countries. Assessments focus on the change in the number of family, work, and return migrants, the number of refugees, and the likelihood of achieving safe, orderly, and regular migration. Experts were at the moment of the survey active in European research centers or European (supra-) national governmental or civil society organizations. The survey features a factorial design, which allows for identifying a causal relationship between the experts' assessments and the scenarios of social change. Our data may be used to estimate projection models of future migration flows, map out what experts consider as critical migration issues for the region, and identify areas of agreement or disagreement between them. As such, our dataset may illuminate decision-making regarding migration policies in Europe and beyond.

Effects of a home-based palliative heart failure program on quality of life among the elderly: a clinical trial study.

INTRODUCTION: One of the frequent issues that lowers elderly people's quality of life is chronic heart failure, a progressive and life-limiting disease. The purpose of this study was to evaluate the effects of home-based palliative care (HBPC) on the quality of life of elderly patients with heart failure who received discharge orders from hospitals affiliated with Kerman University of Medical Sciences in 2022. METHODS: One hundred heart failure patients were divided into two intervention and control groups for this randomized clinical trial study. The patients were then given the pre-test questionnaires, such as the demographic questionnaire and the Quality of Life Index (QLI) by Ferrans and Powers. The intervention group was given the home care plan. To measure the quality of life one month after the intervention, the quality of life questionnaire was lastly filled out by both groups following the last care session. Software called SPSS 22 was used to enter and analyze the patient data. RESULTS: The mean age for the elderly in the intervention and in the control groups were 69.46 ± 11.61 and 66.14 ± 12.09 years, respectively. The palliative care program at home made a statistically significant difference in the quality of life and all of its components in the elderly with heart failure in the intervention group immediately after the intervention and one month after the intervention compared to before (P < 0.001). As a result, its scores improved compared to the stage before the intervention. Additionally, a significant difference between the quality of life score and all of its components between the intervention's immediate aftermath and one month later was noted (P < 0.05). CONCLUSION: Home-based palliative care has a positive effect on the quality of life for elderly people who have heart failure, making it a worthwhile intervention to enhance their quality of life. TRIAL REGISTRATIONS: (IRCT20211213053389N1). Date of registration: (19/02/2022).

The Automated Systematic Search Deduplicator (ASySD): a rapid, open-source, interoperable tool to remove duplicate citations in biomedical systematic reviews.

BACKGROUND: Researchers performing high-quality systematic reviews search across multiple databases to identify relevant evidence. However, the same publication is often retrieved from several databases. Identifying and removing such duplicates ("deduplication") can be extremely time-consuming, but failure to remove these citations can lead to the wrongful inclusion of duplicate data. Many existing tools are not sensitive enough, lack interoperability with other tools, are not freely accessible, or are difficult to use without programming knowledge. Here, we report the performance of our Automated Systematic Search Deduplicator (ASySD), a novel tool to perform automated deduplication of systematic searches for biomedical reviews. METHODS: We evaluated ASySD's performance on 5 unseen biomedical systematic search datasets of various sizes (1845-79,880 citations). We compared the performance of ASySD with EndNote's automated deduplication option and with the Systematic Review Assistant Deduplication Module (SRA-DM). RESULTS: ASySD identified more duplicates than either SRA-DM or EndNote, with a sensitivity in different datasets of 0.95 to 0.99. The false-positive rate was comparable to human performance, with a specificity of > 0.99. The tool took less than 1 h to identify and remove duplicates within each dataset. CONCLUSIONS: For duplicate removal in biomedical systematic reviews, ASySD is a highly sensitive, reliable, and time-saving tool. It is open source and freely available online as both an R package and a user-friendly web application.

Ethical Imperatives for Working With Diverse Populations in Digital Research.

Digital research methodologies are driving a revolution in health technology but do not yet fully engage diverse and historically underrepresented populations. In this paper, we explore the ethical imperative for such engagement alongside accompanying challenges related to recruitment, appreciation of risk, and confidentiality, among others. We critically analyze existing research ethics frameworks and find that their reliance on individualistic and autonomy-focused models of research ethics does not offer adequate protection in the context of the diversity imperative. To meet the requirements of justice and inclusivity in digital research, methods will benefit from a reorientation toward more participatory practices.

The effect of the Er,Cr:YSGG laser combined casein phosphopeptide amorphous calcium phosphate for enamel remineralisation: a systematic review and meta-analysis of in vitro studies.

The purpose of this systematic review and meta-analysis of in vitro studies was to evaluate the effect of the 2780 nm Er,Cr:YSGG laser combined with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for enamel remineralisation. The electronic PubMed, Cochrane Library, Web of Science, and EMBASE databases were searched, with no language or date restrictions, up to January 2023. Two reviewers independently performed research information extraction and quality assessment. Continuous variables were analysed by standard mean difference (SMD) with a 95% confidence interval (CI). The statistical analyses were conducted using Review Manager (Version 5.4; Rev Man) and Cochrane Collaboration (2020). Finally, four trials were included for meta-analysis. According to the comprehensive results, the effect of the Er,Cr:YSGG laser combined with CPP-ACP on enamel remineralisation was significantly better than that of CPP-ACP alone: surface microhardness (SMD = - 1.83, 95% CI: [- 2.98, - 0.69], P = 0.002); lesion depth (SMD = 6.63, 95% CI: [4.98, 8.28], P < 0.001). Under the limitations of this meta-analysis, the results show that the Er,Cr:YSGG laser combined with CPP-ACP has a better effect on enamel remineralisation than CPP-ACP alone. The combination of the Er,Cr:YSGG laser and CPP-ACP may be a feasible method to prevent and treat enamel demineralisation.

The global prevalence of oral leukoplakia: a systematic review and meta-analysis from 1996 to 2022.

BACKGROUND: Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence. METHODS: The search terms ("Oral leukoplakia" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0. RESULTS: We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not. CONCLUSION: Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia.

An intelligent data analysis-based medical management method for lower limb health of football athletes.

With increasingly mature commercial operations, football has become the most popular sport in the world. As the main body of football, athletes are prone to injury due to an increasing degree of competition intensity. Their health determines the length of these athletes careers, especially regarding the lower limbs that are mainly used. Therefore, the smart visualization approaches that can realize such function are in urgent demand in the area of sports healthcare. Benefitted by the strong ability of perception and analysis, a convolutional neural network (CNN) is utilized to construct an intelligent data analysis-based medical management method for the lower limb health of football athletes. First, the CNN is formulated as the main backbone, and its parameters are optimized for multiple rounds during the training stage. Then, a statistical analysis software named SPSS is introduced to assess the effect mechanism of different postures on lower limbs. Some experiments are carried out on simulative data to evaluate the proposed method, and results show a good performance of the proposed method.

A normalized differential sequence feature encoding method based on amino acid sequences.

Protein interactions are the foundation of all metabolic activities of cells, such as apoptosis, the immune response, and metabolic pathways. In order to optimize the performance of protein interaction prediction, a coding method based on normalized difference sequence characteristics (NDSF) of amino acid sequences is proposed. By using the positional relationships between amino acids in the sequences and the correlation characteristics between sequence pairs, NDSF is jointly encoded. Using principal component analysis (PCA) and local linear embedding (LLE) dimensionality reduction methods, the coded 174-dimensional human protein sequence vector is extracted using sequence features. This study compares the classification performance of four ensemble learning methods (AdaBoost, Extra trees, LightGBM, XGBoost) applied to PCA and LLE features. Cross-validation and grid search methods are used to find the best combination of parameters. The results show that the accuracy of NDSF is generally higher than that of the sequence matrix-based coding method (MOS) coding method, and the loss and coding time can be greatly reduced. The bar chart of feature extraction shows that the classification accuracy is significantly higher when using the linear dimensionality reduction method, PCA, compared to the nonlinear dimensionality reduction method, LLE. After classification with XGBoost, the model accuracy reaches 99.2%, which provides the best performance among all models. This study suggests that NDSF combined with PCA and XGBoost may be an effective strategy for classifying different human protein interactions.

Communication in Sudden-Onset Major Incidents: Patterns and Challenges-Scoping Review.

OBJECTIVE: To identify and describe patterns and challenges in communication in sudden-onset major incidents. METHODS: Systematic scoping review according to Joanna Briggs Institute and PRISMA-ScR guidelines. Data sources included Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, SweMed+, Web of Science, and Google Scholar. Non-indexed literature was searched as well. The included literature went through data extraction and quality appraisal as per pre-registered protocol. RESULTS: The scoping review comprised 32 papers from different sources. Communication breakdown was reported in 25 (78.1%) of the included papers. Inter-authority communication challenges were reported in 18 (56.3%) of the papers. System overload and incompatibility was described in 9 papers (28.1%). Study design was clearly described in 30 papers (93.8%). CONCLUSIONS: The pattern in major incident communication is reflected by frequent breakdowns with potential and actual consequences for patient survival and outcome. The challenges in communication are predominantly inter-authority communication, system overload and incompatibility, and insufficient pre-incident planning and guidelines.

Methods to predict the timing and status of biological maturation in male adolescent soccer players: A narrative systematic review.

The aim of this review was to summarise the methods used to predict and assess maturity status and timing in adolescent, male, academy soccer players. A systematic search was conducted on PubMed, Scopus, Web of Science, CINAHL, Medline and SPORTDiscus. Only experimental studies including male, academy players aged U9-U18 years registered with a professional soccer club were included. The methodological quality of the included studies was assessed using guidelines from the Framework of Potential Biases. Fifteen studies fulfilled our inclusion criteria. Studies were mainly conducted in European countries (n = 12). In total, 4,707 players were recruited across all 15 studies, with an age range of 8-18 years. Five studies were longitudinal, two studies were mixed-method designs and eight studies were cross-sectional. Due to high heterogeneity within the studies, a meta-analysis was not performed. Our findings provided no equivalent estimations of adult height, skeletal age, or age at PHV. Discrepancies were evident between actual and predicted adult height and age at PHV. The Bayley-Pinneau [1952], Tanner-Whitehouse 2 [1983] and Khamis-Roche [1994] methods produced estimates of adult height within 1cm of actual adult height. For age at PHV, both Moore [2015] equations produced the closest estimates to actual age at PHV, and the Fransen [2018] equation correlated highly with actual age at PHV (>90%), even when the period between chronological age and age at PHV was large. Medical imaging techniques (e.g., Magnetic Resonance Imaging, X-Ray, Dual energy X-ray Absorptiometry) demonstrated high intra/inter-rater reliability (ICC = 0.83-0.98) for skeletal maturity assessments. The poor concordance between invasive and non-invasive methods, is a warning to practitioners to not use these methods interchangeably for assessing maturational status and timing in academy soccer players. Further research with improved study designs is required to validate these results and improve our understanding of these methods when applied in this target population.

Using public clinical trial reports to probe non-experimental causal inference methods.

BACKGROUND: Non-experimental studies (also known as observational studies) are valuable for estimating the effects of various medical interventions, but are notoriously difficult to evaluate because the methods used in non-experimental studies require untestable assumptions. This lack of intrinsic verifiability makes it difficult both to compare different non-experimental study methods and to trust the results of any particular non-experimental study. METHODS: We introduce TrialProbe, a data resource and statistical framework for the evaluation of non-experimental methods. We first collect a dataset of pseudo "ground truths" about the relative effects of drugs by using empirical Bayesian techniques to analyze adverse events recorded in public clinical trial reports. We then develop a framework for evaluating non-experimental methods against that ground truth by measuring concordance between the non-experimental effect estimates and the estimates derived from clinical trials. As a demonstration of our approach, we also perform an example methods evaluation between propensity score matching, inverse propensity score weighting, and an unadjusted approach on a large national insurance claims dataset. RESULTS: From the 33,701 clinical trial records in our version of the ClinicalTrials.gov dataset, we are able to extract 12,967 unique drug/drug adverse event comparisons to form a ground truth set. During our corresponding methods evaluation, we are able to use that reference set to demonstrate that both propensity score matching and inverse propensity score weighting can produce estimates that have high concordance with clinical trial results and substantially outperform an unadjusted baseline. CONCLUSIONS: We find that TrialProbe is an effective approach for probing non-experimental study methods, being able to generate large ground truth sets that are able to distinguish how well non-experimental methods perform in real world observational data.

ASSOCIATION OF ORAL MICROBIOTA AND PERIODONTAL DISEASE WITH LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Evidence of oral microbiota perturbations has been accumulated for lung cancers. This review focused on the oral microbiota alterations in population suffering from lung cancer. In addition, we also discussed conflicting data about the association between oral microbiota dysbiosis and risk of lung cancer. METHODS: A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. The studies evaluated diversity and abundance of oral microbes in healthy and lung cancer individuals as well as association of periodontal disease and pathogens with lung cancer. Of 3559 studies, 28 included studies were performed in qualitative analysis, and 25 studies were used in meta-analyses for quantitative assessment. Heterogeneity was analyzed by using I² and chi-squared Q test statistics. Statistical analyses were performed by using the RevMan 5.4 software. RESULTS: Compared with the control, lung cancer patients had lower alpha diversity (Shannon: SMD = -0.54; 95% CI, -0.90 to -0.19; P < .01, I2 = 71%). In nested case-control studies, individuals with decreased alpha diversity tended to have an increased risk of lung cancer (observed species: HR = 0.90; 95% CI, 0.85-0.96; P < .01, I2 = 0%; Shannon: HR = 0.89; 95% CI, 0.83-0.95; P < .01, I2 = 0%). Overall, no strong evidence of association of relative abundance with specific oral microbes with lung cancers was found because of inconsistent data. No associations were found between periodontal pathogens and lung cancer risk (red complex: HR = 1.12, 95% CI: 0.42-3.02, P = .82, I2 = 62%; orange complex: HR =1.77, 95% CI: 0.78-3.98, P = .17, I2 = 36%), expect for Fusobacterium nucleatum (HR = 2.27, 95% CI: 1.13-4.58, P = .02, I2 = 0%). The positive association of periodontal disease with lung cancer risk was found (HR = 1.58, 95% CI: 1.25-2.00, P < .001, I2= 0%) with increase of periodontal diseases severity (HR = 2.39, 95% CI: 1.57-3.66, P < .001, I2 = 0%). However, such association was not found in never-smoker participants (HR = 1.00, 95% CI: 0.76-1.31, P = .37, I2= 7%). CONCLUSIONS: Lower alpha diversity of oral microbiome may be associated with a greater risk of lung cancer and might serve as a predictive signal of lung cancer risk. There was no strong evidence of relative abundance of oral microbial taxa and periodontal pathogens in lung cancer patients. Fusobacterium nucleatum might be a potential microbial candidate of biomarkers in lung cancer. Periodontal disease may be positively associated with lung cancer risk by confounding of smoking, but not an independent risk factor.

Hypnotic suggestion versus sensory modulation of bodily awareness.

Bodily awareness arises from somatosensory, vestibular, and visual inputs but cannot be reduced to these incoming sensory signals. Cognitive factors are known to also impact bodily awareness, though their specific influence is poorly understood. Here we systematically compared the effects of sensory (bottom-up) and cognitive (top-down) manipulations on the estimated size of body parts. Toward this end, in a repeated-measures design, we sought to induce the illusion that the right index finger was elongating by vibrating the biceps tendon of the left arm whilst participants grasped the tip of their right index finger (Lackner illusion; bottom-up) and separately by hypnotic suggestion (top-down), with a sham version of the Lackner illusion as an active control condition. The effects of these manipulations were assessed with perceptual and motor tasks to capture different components of the representation of body size. We found that hypnotic suggestion significantly induced the illusion in both tasks relative to the sham condition. The magnitudes of these effects were stronger than those in the Lackner illusion condition, which only produced a significantly stronger illusion than the sham condition in the perceptual task. We further observed that illusion magnitude significantly correlated across tasks and conditions, suggesting partly shared mechanisms. These results are in line with theories of separate but interacting representational processes for perception and action and highlight the influence of cognitive factors on low-level body representations.

A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations.

The polyaneuploid cancer cell (PACC) state promotes cancer lethality by contributing to survival in extreme conditions and metastasis. Recent experimental evidence suggests that post-therapy PACC-derived recurrent populations display cross-resistance to classes of therapies with independent mechanisms of action. We hypothesize that this can occur through PACC memory, whereby cancer cells that have undergone a polyaneuploid transition (PAT) reenter the PACC state more quickly or have higher levels of innate resistance. In this paper, we build on our prior mathematical models of the eco-evolutionary dynamics of cells in the 2N+ and PACC states to investigate these two hypotheses. We show that although an increase in innate resistance is more effective at promoting cross-resistance, this trend can also be produced via PACC memory. We also find that resensitization of cells that acquire increased innate resistance through the PAT have a considerable impact on eco-evolutionary dynamics and extinction probabilities. This study, though theoretical in nature, can help inspire future experimentation to tease apart hypotheses surrounding how cross-resistance in structured cancer populations arises.

Effectiveness of a social-emotional learning program on developmental assets and subjective well-being.

The present study was done to evaluate the effectiveness of a Social Emotional Learning (SEL) intervention designed based on social marketing on developmental assets and the well-being of female adolescents in Yazd, Iran. This mixed-method quasi-experimental study was conducted in 2018-2019. A total of 190 female students were selected by multi-stage sampling from the female middle and high schools in Yazd, Iran. A SEL intervention designed based on social marketing principles was implemented among the parents and students of the intervention group. The control group did not receive any intervention. Quantitative data were collected in three stages: pre-test, post-test after two months, and follow-up after six months via Developmental Assets Profile and EPOCH measure of wellbeing. A qualitative evaluation was also performed after the intervention. Results of the Repeated-Measures test indicated that the intervention significantly influenced social competence (p-value = .02). However results did not show improvement in the positive identity development of the participant girls. Qualitative findings suggested the effectiveness of the intervention on social competencies and positive identity. Based on the results of the present study, the SEL program might have a significant but small positive effect on the social competencies of the participating adolescents.

Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy.

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.

Socioeconomic disparities in Rwanda's under-5 population's growth tracking and nutrition promotion: findings from the 2019-2020 demographic and health survey.

BACKGROUND: Regular growth monitoring can be used to evaluate young children's nutritional and physical health. While adequate evaluation of the scope and quality of nutrition interventions is necessary to increase their effectiveness, there is little research on growth monitoring coverage measurement. The purpose of this study was to investigate socioeconomic disparities in under-5 Rwandan children who participate in growth monitoring and nutrition promotion. METHODS: We used data from the 2019-2020 Rwanda Demographic and Health Survey (RDHS), which included 8092under-5 children. Percentage was employed in univariate analysis. To examine the socioeconomic inequalities, concentration indices and Lorenz curves were used in growth monitoring and nutrition promotion among under-5 children. RESULTS: A weighted prevalence of 33.0% (95%CI: 30.6-35.6%) under-5 children growth monitoring and nutrition promotion was estimated. Growth monitoring and nutrition promotion among under-5 children had higher uptake in the most disadvantaged cohort, as the line of equality sags below the diagonal line in Lorenz curve. Overall, there was pro-poor growth monitoring and nutrition promotion among under-5 in Rwanda (Conc. Index = 0.0994; SE = 0.0111). Across the levels of child and mother's characteristics, the results show higher coverage of under-5 growth monitoring and nutrition promotion in the most socioeconomic disadvantaged cohort. CONCLUSION: The study found a pro-poor disparity in growth monitoring and nutrition promotion among under-5 children in Rwanda. By implication, the most disadvantaged children had a higher uptake of growth monitoring and nutrition promotion. The Rwanda government should develop policies and programmes to achieve the universal health coverage for the well-off and underserved population.

Agreements and differences between psychoanalysts with regard to changes observed during a treatment. A quantitative exploration using the Three-Level Model (3-LM).

The aim of this paper is to report the partial results of an exploratory investigation into how twelve psychoanalysts of different theoretical-clinical orientations perceive and use hypotheses about the phenomena of change in connection with selected material from a psychoanalytic treatment. The Three-Level Model (3-LM) was used for the observation of patient transformations and for the collection of data. This was followed by the statistical analysis of the behaviour and relationship of a set of variables relating to the type and degree of change perceived in the patient's mental functioning during the course of her treatment. The results reported here show that there was significant agreement among the participants, irrespective of their theoretical-clinical orientation, as regards the following: 1) the positive impact of the application of psychoanalytic treatment in diverse areas of the patient's mental functioning; 2) the explanatory hypotheses of the changes observed in the patient under consideration; 3) the usefulness of the experience of group exchange using the 3-LM in observing and understanding the changes in the patient.

The unblinding of statisticians in clinical trials: commentary on Iflaifel et al., Trials 2023.

Recently, the Blinding of Trial Statisticians research team, Iflaifel and colleagues, have produced detailed guidance regarding the blinding or unblinding of statisticians in clinical trials, based on substantial mixed-methods work. I wish to comment on the research findings. In particular, I argue that open-label trials, non-drug trials, or non-inferiority trials should not be treated any differently from blinded superiority trials with regards to the risk of bias assessment. Prevention of bias should be the priority for definitive randomised controlled trials, regardless of the precise study design.