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<sup>h</sup>InGeTox: a human-based in vitro platform to evaluate lentivirus/host interactions that contribute to genotoxicity
No full textLentivirus vectors are effective for treatment of genetic disease. However, safety associated with vector related genotoxicity is of concern and currently available models are not reliably predictive of safety in humans. We have developed hInGeTox as the first human in vitro platform that uses induced pluripotent stem cells and their hepatocyte like cell derivatives to better understand vector-host interactions that relate vectors to their potential genotoxicity. Using lentiviral vectors carrying the eGFP expression cassette under SFFV promoter activity, that only differ by their LTR and SIN configuration, we characterised vector host interactions potentially implicated in genotoxicity. To do this, lentiviral infected cells were subjected to an array of assays and data from these was used for multi-omics analyses of vector effects on cells at early and late harvest time points. Data on the integration sites of lentiviral vectors in cancer genes and differential expression levels of these genes, showed that both vector configurations are capable of activating cancer genes. Through IS tracking in bulk infected cell populations, we also saw an increase in the viral sequence count in cancer genes present over time which were differentially regulated. RNASeq also showed each vector had potential to generate fusion transcripts with the human genome suggestive of gene splicing or vector mediated readthrough from the internal SFFV promoter. Initially, after infection, both vector configurations were associated with differential expression of genes associated cytokine production, however, after culturing over time there were differences in differential expression in cells infected by each LV. This was marked in particular by the expression of genes involved in the response to DNA damage in cells transduced by the SIN vector, suggesting effects likely to prevent tumour development, in contrast to the expression of genes involved in methylation, characteristic of tumour development, in cells transduced by the LTR vector. Both sets of lentiviral infected cells were also found associated with differential expression of MECOM and LMO2 genes known to be associated with clonal dominance, supporting their potential genotoxicity. Alignment of transcriptomic signatures from iPSC and HLC infected cultures with known cancer gene signatures showed the LTR vector with a higher cancer score than the SIN vector over time in iPSC and also in HLC, which further suggests higher genotoxic potential by the LTR configuration lentivirus. By application of hInGeTox to cells infected with LV at the pre-clinical stage of development, we hope that hInGeTox can act as a useful pre-clinical tool to identify lentivirus-host interactions that may be considered contributory to genotoxicity to improve safer lentiviral vector design for gene therapy.</p
Estimation of premorbid intelligence in schizophrenia: a systematic literature review
No full textIntroduction: Cognitive impairment is a commonly observed characteristic of people living with schizophrenia (PLWS). Adequate monitoring of intellectual decline and status in this population requires reliable estimates of premorbid IQ because objective IQ data predating schizophrenia onset are often unavailable. However, premorbid IQ estimation in PLWS is frequently complicated by confounding factors. The primary objective of this systematic review is to explore and compare extant approaches for estimating premorbid IQ in PLWS and, in doing so, identify factors that might inform the selection of the most reliable method for this clinical population. Method: A systematic literature search was conducted across PubMed, Web of Science Core Collection, EBSCOhost, SCOPUS, and The Cochrane Library electronic bibliographic databases. After deduplication, study selection was conducted in line with predefined inclusion and exclusion criteria. The quality assessment of studies was conducted using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. Results: 43 articles involving 8,012 participants with schizophrenia spectrum disorders were included. Premorbid IQ estimation methods such as the National Adult Reading Test (NART), Wide Range Achievement Test (WRAT), Test of Premorbid Functioning (ToPF), Wechsler Test of Adult Reading (WTAR), Oklahoma Premorbid Intelligence Estimate (OPIE), demographic regression algorithms, and “hold” test approaches based on subtests from the Wechsler Adult Intelligence Scale (WAIS) were employed. Studies comparing these methods report inconsistent levels of agreement, with differences associated with factors such as schizophrenia chronicity, age of onset, and years of education. Conclusions: A range of measures are available for estimating premorbid IQ in people living with schizophrenia. However, their precision is limited by several factors identified in this review. We urge researchers and clinicians to recognize these limitations. We have created an evidence-based guide to support the selection of the most optimal estimation method for premorbid IQ in PLWS.</p
Family history of non-communicable diseases and the risk of cardiovascular-kidney-metabolic syndrome
No full textCardiovascular-kidney-metabolic (CKM)-related diseases are known to be influenced by family history; however, few studies have analyzed associations between them. Thus, this study aims to analyze associations between family history of non-communicable diseases with CKM-related diseases and CKM stages. This study utilized data from the Korea National Health and Nutrition Examination Survey to calculate the weighted prevalence and 95% confidence intervals (CI) of CKM syndrome and CKM-related diseases based on family history of non-communicable diseases including hypertension, diabetes, hyperlipidemia, ischemic heart disease, and stroke. Adjusted odds ratios() with 95% CI were calculated using multivariable logistic regression and partial proportional odds models. CKM syndrome was classified according to the criteria established by the American Heart Association (early-advanced stage, 0–4). This study analyzed family history, prevalence rates of CKM-related diseases, and CKM syndrome stages in 57,340 participants. The results indicated higher prevalence rates for individuals with a family history of CKM-related diseases. Furthermore, individuals with such a history were at greater risk of being classified into more advanced stages of CKM syndrome compared to those without. In particular, when focusing on the most advanced stage (stage ≥ 4) of CKM syndrome, a family history of hypertension increased the risk by 43% (95% CI, 32–54), diabetes by 54% (41–67), hyperlipidemia by 97% (41–67), ischemic heart disease by 147% (123–173), and stroke by 106% (90–124). The family history of CKM-related diseases may increase the prevalence of these diseases and influence CKM syndrome progression stages. These findings suggest implementing early diagnosis and management programs that take family history into account.</p
Correction: Orofino (2024). “Groups are still a problem … but a different one!”: reflecting on the role played by non-violent extremist groups in the radicalisation pathways of individuals in the UK. Social Sciences 13: 424
No full textThe academic editor chose not to show her/his name [...]</p
Artificial Intelligence (AI) and the future of information privacy: Experts viewpoints
No full textAI's expanding role in daily life offers data-driven decision-making but risks privacy breaches.
This study, using the Communication Privacy Management Theory, explores AI adoption's future
privacy implications. Through thematic analysis of 42 AI expert interviews, we identify six key
themes: human agency, data use/abuse, AI transparency/opacity, information weaponization,
cyberbullying, and privacy enforcement. These themes contextualize the evolving AI-privacy
relationship. We argue that AI's advancement will challenge traditional privacy ownership
concepts. This research provides insights into navigating the complex interplay between AI's
growth and safeguarding information privacy.</p
Evidence That Tetris Reduces Immediate but Not Subsequent Daily Intrusions of a Trauma Film: A Multilab Replication Study
No full textReactivating a target memory and subsequently playing the computer game Tetris is thought to reduce intrusive memories and is being explored clinically. However, the current literature on the effect of Tetris on intrusions has limitations. To examine whether the previous finding from experimental research that Tetris reduces trauma film related intrusions is replicable in a large sample, we conducted a preregistered, multi-site study in healthy participants. Experiment 1 (N = 141) showed similar intrusion rates of an updated trauma film that was then used in Experiment 2. In line with previous findings, Experiment 2 (N = 433) showed that compared to a perceptual vigilance control task, Tetris reduced retrospective ratings of trauma film related intrusions during the task. In contrast to such an immediate effect, the hypothesis that Tetris reduces intrusions over the course of one week was not corroborated. Future research may examine the role of the format of delivering the experiment (i.e., in-person versus online sessions) and type of control condition (i.e., no-task versus active control). This may inform studies on whether, and in what settings, Tetris is a suitable intervention for clinical use.</p
Effect of a multi-ingredient post-workout dietary supplement on body composition and muscle strength – a randomized controlled trial
No full textThe aim of the current parallel randomized controlled trial was to compare the effects of ingesting a dietary supplement admixture providing carbohydrates, leucine-fortified whey protein, creatine, β-hydroxy-β-methylbutyrate, and vitamin D3 (Master Recovery 1:1, Crown Sport Nutrition, Spain), versus an isoenergetic carbohydrate-only comparator on body composition, muscle thickness, muscle strength, and performance over a 6-week resistance training program, performed three times per week, in aging, physically active individuals. Twenty participants (10 peri- and post-menopausal females and 10 males) completed the study after being randomly assigned to one of the following groups: post-workout multi-ingredient (PWS: n = 10, 52.0 ± 5 years, body mass 82.0 ± 18.0 kg) or a comparator (COM: n = 10, 51 ± 3 years, body mass 85.9 ± 17.0 kg). Treatment consisted of ingesting 60.0 g of the assigned supplement immediately after each workout. Compared to baseline, only PWS increased fat-free mass (+1.34 ± 1.2 kg, p = 0.003), reduced fat mass (–1.09 ± 0.7 kg, p < 0.001), waist circumference (–2.5 ± 1.8 cm, p < 0.001), and waist-to-hip ratio (–0.03 ± 0.03 cm, p = 0.007). At post-intervention, waist circumference reduction was different between groups (p = 0.02, d = 1.19). Both treatments similarly improved vastus lateralis and elbow flexor thickness, medicine ball throw, and endurance performance. Although countermovement jump improved for both treatments, the PWS group showed a significantly higher performance increase compared to COM (p < 0.01, d = 1.47). Compared to ingesting carbohydrates only, the use of a targeted multi-ingredient promoted noticeable body composition outcomes and better vertical jump improvements with no further effects on hypertrophy, upper body, and endurance performance. The study was registered as a clinical trial at ClinicalTrials.gov (NCT05769088).</p
Systematic review of contemporary outcomes for medical management of symptomatic patients with moderate to severe carotid stenosis
No full textIntroduction: Medical therapy for secondary prevention of stroke has evolved markedly since the landmark North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial 1 (ECST-1) carotid surgery trials. The aim of this study was to perform a systematic review of stroke outcomes in adults with recent stroke or transient ischemic attack (TIA) with 50-99% carotid stenosis, treated with modern medical therapy over the last decade.Evidence acquisition: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using a predefined search strategy on MEDLINE, EMBASE, Google Scholar, The Cochrane Database and clinicaltrials.gov. Inclusion criteria were studies of symptomatic patients with 50-99% carotid atherosclerotic stenosis published since 2015.Evidence synthesis: Six completed studies gave original data on stroke and TIA outcomes. In general, the risk of bias was moderate to high. One-month stroke outcomes were reported as 1%, at 3 months 2%, at 1 year 10% and at 2 years 13%.Conclusions: Modern medical therapy, along with improvements in hyperacute stroke care, may have reduced the early risks associated with carotid plaque rupture. This in turn has implications for the role of carotid endarterectomy.</p
Corporate governance and sustainability disclosure: challenges and opportunities for the Libyan Audit Bureau in the oil sector
No full textThis study identifies challenges faced by Libyan Audit Bureau (LAB) members in monitoring governance practices and sustainability disclosure in Libya's oil sector. Using quantitative data from 231 distributed questionnaires (88% response rate), the research reveals that LAB oversight remains in early stages due to persistent challenges including regulatory gaps, weak enforcement, insufficient professional standards, and cultural-institutional barriers. While international benchmarks such as IFRS S1 and S2 gain worldwide adoption, Libya's implementation remains limited. Enhanced LAB effectiveness requires policies addressing stakeholder rights, Islamic principles integration, transparency mechanisms, conflict management, and external factors including professional development, legal system strengthening, enforcement improvement, cultural considerations, and awareness building for governance and sustainability reporting.</p
Global, regional, national burden of headache disorders, 1990-2021, with forecasts to 2050: a Global Burden of Disease Study 2021
No full textHeadache disorders, especially migraines and tension-type headaches (TTHs), are major global public health concerns, as shown by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. We provide updated global estimates of prevalence and years lived with disability (YLDs) from 1990 to 2021 across 204 countries and territories and forecasts through 2050. In 2021, there are 2.0 billion people with TTH and 1.2 billion with migraine. Although TTH is more prevalent, migraine causes higher disability. While crude prevalence and YLDs increased, age-standardized rates remained stable and are projected to continue this trend due to population growth. There is a disproportionately higher burden in women aged 30–44 and countries with higher Socio-demographic Index and Healthcare Access and Quality Index. Despite this, migraines remain underrecognized in health policies and funding. This study emphasizes the urgent need to prioritize headache disorders in global health agendas.</p
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