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Nicotine pouches, oral cancer and tobacco harm reduction:current evidence and research priorities
Get PDFTobacco smoking remains the most consistent and preventable risk factor for oral cancer, driven by exposure to combustion-derived toxins that promote DNA damage, inflammation and microbiota dysregulation. Global data show substantial geographic variability in disease burden, with particularly high incidence and mortality especially in South and Southeast Asia, where culturally reinforced and deeply embedded forms of high-nitrosamine smokeless tobacco and areca nut continue to drive risk. In this evolving landscape, nicotine pouches have rapidly expanded as tobacco-free oral products manufactured to deliver nicotine without combustion. Toxicological analyses reveal significantly lower levels of harmful constituents relative to cigarettes and traditional smokeless tobacco, and short-term clinical studies report reductions in oral mucosal irritation and gingival inflammation among exclusive users. However, no long-term epidemiological evidence is currently available to assess their potential impact upon oral carcinogenesis, and existing human studies remain few, small and heterogeneous. This mini review highlights critical priorities for research, including the need for long-term prospective studies, standardized product testing, independent toxicological assessments and surveillance of patterns of use, dual use and youth uptake. The integration of harm reduction approaches with established prevention strategies may offer opportunities to mitigate oral cancer risk in adults who smoke and/or consume unregulated smokeless tobacco products with high risk profiles that are very common in Asia, the Middle East and Africa. However, this approach requires cautious interpretation of the current evidence and ongoing monitoring of emerging products
Central Questions for Social Neuroscience Research
Get PDFOver the past decade, interest in social neuroscience has expanded rapidly. This growth raises a fundamental inquiry: what are the central questions that now define the field of social neuroscience? While the answer to this question depends on the appropriate neurobiological level of explanation, ranging from cellular substrates to systems and network-level dynamics, there are commonalities that transcend multiple levels. One longstanding question in the field of social neuroscience concerns whether there is social specificity in the brain. If a neural substrate exhibits social specificity, does it do so at the algorithmic level, the implementational level, or both? Another emerging question concerns how neural systems construct and update internal models of the social world composed of other agents and factors of one's social environment. These internal models of the social world must integrate social information throughout one's lifespan, adding a critical developmental component in building social world models. Relatedly, another core question concerns internal states that dynamically guide social behavior and social cognition. These internal states may have components that are innately driven or acquired by learning in the social world. With powerful neuroscientific tools and behavioral sophistications, the field is gaining a great amount of traction to begin to answer such central questions. This special collection brings together seven selected contributions that reflect cutting-edge and cross-species research in the field of social neuroscience. As editors, we encourage readers to consider the aforementioned and other big-picture questions in social neuroscience as they engage with the manuscripts in this issue.</p
Hospital preparedness exercises for paediatric mass casualty incidents:a systematic review
Get PDFIntroduction: Mass casualty incidents (MCIs) present a global threat to civilians, with children often being affected and sometimes even targeted; however, there is little research regarding the preparedness exercises of healthcare professionals for such events. Methods: A systematic search of PubMed, Web of Science and Embase from inception up to July 2025, was conducted. Risk of bias was also assessed using the risk of bias in non-randomised studies of interventions exposure (ROBINS E) tool. Results: The initial search generated 223 results, and following double screening and manual citation searching, 17 observational studies were selected for narrative synthesis, since numerical data to perform meta-analysis were unavailable. The review identified a broad range of training interventions tailored for paediatric MCIs. Both brief, frequent drills and longer, mixed methods training schemes were effective, yielding gains in specific skills and a holistic sense of preparedness, including teamwork and communication. These improvements were often sustained for up to 6 months, despite a common limitation of lost to follow-up. However, the overall risk of bias in the included studies were high to very high. Discussion: MCI educational schemes appear to improve all aspects of preparedness. However, the evidence is heterogeneous, lacked standardisation in the outcome measures and contained high to very high risk of bias, suggesting that the current evidence cannot support definitive recommendations. Future research should aim to conduct high-quality studies with standardised outcome assessment tools to optimise paediatric MCI preparedness.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251084048
Immunomodulators in Graves’ ophthalmopathy:a systematic review
Get PDFBackground: Graves’ Ophthalmopathy (GO), or thyroid eye disease, is an extrathyroidal complication of Graves’ disease, causing a significant impact on patients’ quality of life. There are consensus statements from both the American Thyroid Association (ATA) and the European Group on Graves’ Orbitopathy (EUGOGO) which provide guidance in management. However, there remain areas of ongoing debate and evolution in treatment approaches. This systematic review aims to evaluate immunomodulatory drugs in the treatment of GO. Methods: The following databases were searched: Cochrane (CENTRAL), Embase, MEDLINE, ProQuest, PubMed, SCOPUS, and Web of Science. The last date of searching for each database was 10th October 2025. All primary studies on human patients with GO, treated with newer, targeted immunomodulatory therapies, in particular biologics and/or disease-modifying antirheumatic drugs, were included. Studies in languages other than English were excluded. The primary outcome of interest was Clinical Activity Score (CAS). A narrative synthesis was performed, including CAS and four other secondary outcomes. Cochrane risk of bias tools were used to assess quality of evidence. The study is registered on PROSPERO (CRD42023400285). Results: Of 4839 records identified, 41 were eligible for data extraction. Teprotumumab and tocilizumab showed benefit in reducing CAS and proptosis, whilst rituximab was inconclusive. Methotrexate and reduced-dose steroids were beneficial in reducing CAS, and both methotrexate and cyclosporine with steroids were good for reducing proptosis. However, effects of immunomodulation on other secondary outcomes were unclear. Adverse events were higher in the steroid treated patients compared to all other drugs. Conclusion: Biologics and steroid-sparing agents may be more effective than steroids at reducing CAS, but this is limited by the lack of head-to-head comparisons between drugs and significant heterogeneity amongst the included studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023400285
Mediation effects in blockchain technology adoption for social sustainability:Pre- and post-adoption analysis of existing and future socially sustainable supply chains
Get PDFWhile blockchain technology offers promising potential for enhancing social sustainability in supply chains, its adoption and effective utilisation remain underexplored. This study, grounded in the dynamic capabilities view, investigates the role of social orientation and the cognitive mechanism of Perceived Usefulness in driving blockchain technology adoption, and its subsequent impact on future social practices and social performance across both pre- and post-adoption phases. Using a quantitative survey of UK manufacturing organisations, this study examines the mediating effects of existing social practices in the pre-adoption phase and future social practices in the post-adoption phase. Findings reveal that while social orientation positively influences blockchain adoption, this effect is partially mediated by existing social practices. Furthermore, blockchain implementation acts as a catalyst for the adoption of future social practices, which in turn mediates its impact on social performance. This study contributes to the operations and supply chain management body of literature by: 1) providing empirical evidence for the mediating role of social practices in the relationship between social orientation, blockchain adoption, and social performance; 2) highlighting the dynamic interplay between existing and future social practices in shaping the adoption and impact of blockchain technology, adopting a multi-stage approach that considers both pre- and post-adoption phases; and 3) providing managers with the strategic tool Blockchain Technology for Social Sustainability (BTSS) for leveraging blockchain for social sustainability
A neural signature of adaptive mentalization
Get PDFMentalization, inferring others' emotions and intentions, is crucial for human social interactions and is impaired in various brain disorders. While previous neuroscience research has focused on static mentalization strategies, we know little about how the brain adaptively selects which strategies to use at any given moment. Here we investigate this core aspect of mentalization with computational modeling and functional magnetic resonance imaging (fMRI) during interactive strategic games. We find that most participants can adapt their strategies to the changing sophistication of their opponents, though there are considerable individual differences. Model-based fMRI analyses identify a distributed brain network in which activity and connectivity track this mentalization-belief adaptation. The extent to which people update their beliefs about others' sophistication can be predicted out of sample from neural activity, providing a neural signature of adaptive mentalization. Our model elucidates the neural basis of mentalization ability and provides a method for assessing these capabilities in healthy and clinical populations.</p
Everyday exposures:feasibility of community-based trace metal monitoring using non-invasive bio-sampling in children’s environments, a pilot study
Get PDFChildren are uniquely vulnerable to environmental pollution due to their developing physiology, distinct behaviours, and higher exposure per body mass, and have limited influence over how their environments are designed and managed. However, the real-world feasibility of integrating non-invasive biomonitoring with community-sourced environmental sampling in children’s everyday settings remains under-evaluated. The absence of validated, field-feasible biomonitoring methods for use in schools and homes, limits the early detection of harmful exposures and constrains the development of routine paediatric environmental surveillance. This pilot study evaluated the feasibility of non-invasive bio-sampling to assess trace-metal exposure in 13 UK schoolchildren. Paired urine and exhaled breath condensate (EBC) samples, EBC being a condensed fraction of exhaled respiratory droplets that may reflect airway-level exposure, were collected alongside drinking water and soil from participants’ school and home environments. All samples were analysed for multiple trace elements using inductively coupled plasma mass spectrometry. To relate internal and external measures, Enrichment factors (EFs), were calculated as the ratio of metal concentrations in biological matrices relative to corresponding environmental sources. Despite small sample sizes, meaningful trends emerged. Elevated zinc and copper levels in tap water corresponded to higher urinary concentrations, suggesting urine is a sensitive matrix for waterborne exposure. In contrast low EFs in EBC relative to soil highlight matrix-specific limitations in using soil as a proxy for inhaled exposure in this matrix. The study demonstrates the practical and ethical suitability of non-invasive biomonitoring in paediatric populations, reinforcing the need for improved standardisation and comprehensive metadata collection. Findings support the potential value of integrating non-invasive methods into larger environmental health surveillance efforts involving children. This work contributes a scalable model for child-focused environmental health research that bridges scientific-data with social-justice, environmental education and equity
Does preimplantation genetic testing for aneuploidy improve live birth rate in women diagnosed with recurrent implantation failure:A systematic review and meta‐analysis?
Get PDFIntroduction: The prevalence of unexplained recurrent implantation failure (RIF) is reported as 2%–15% in the literature. The variation in prevalence reflects the heterogeneity in definition. Recent work has suggested unexplained RIF is unlikely to be endometrial or cycle synchronicity related but is, in fact, an embryological phenomenon. The most likely embryological phenomenon is aneuploidy. Preimplantation genetic testing for aneuploidy (PGT‐A) has proven to reduce miscarriage rates in almost all infertility patients, including those with recurrent pregnancy loss, suggesting aneuploidy plays an important role in unsuccessful in vitro fertilization. No guidance for PGT‐A use in RIF exists. This review aimed to address this evidence gap. Material and Methods: A systematic search of Medline, Embase, Web of Science, CINAHL, and Cochrane Database from inception until November 2024 was undertaken. Selection criteria included experimental and observational studies comparing euploid blastocyst transfer using PGT‐A to standard care. The population included those with RIF or undergoing a minimum of three transfers. The primary outcome was cumulative live birth rate (CLBR). The primary aim of this review is to evaluate the impact of PGT‐A on live birth rate (LBR) following a diagnosis of RIF. The secondary aim was to estimate the true prevalence of RIF, using a definition of three failed cycles. A random effects meta‐analysis was conducted reporting pooled odds ratios between groups using IBM SPSS v29.0.2.0 (20). The review was prospectively registered on PROSPERO:CRD42024580037. Results: A total of 13 studies were included with low‐to‐moderate risk of bias. Eleven studies addressed PGT‐A after an RIF diagnosis while two studies addressed RIF prevalence after successive PGT‐A cycles. Four studies reported a statistically significant increase in CLBR with OR 4.23 [95% CI: 2.14, 8.38]. Similar results were seen in studies reporting a single embryo transfer using PGT‐A following an RIF diagnosis, OR 2.79 [95% CI: 1.90, 4.10]. Conclusions: PGT‐A results in a statistically significant increase in both LBR per embryo transfer and CLBR per cycle. This finding supports the hypothesis that RIF may be an embryological phenomenon. Further research is required before routine recommendation of PGT‐A for the management of RIF can be inferred
The use of normal saline instillation as part of endotracheal suction in mechanically ventilated patients:a scoping review
No full textBackground The use of saline instillation (SI) before endotracheal suction (ETS) in mechanically ventilated patients remains contentious, with reasons for SI use/non-use varying amongst ICU clinicians. Methodological heterogeneity in the existing literature makes drawing firm conclusions surrounding SI practice, informing evidenced based practice guidelines and clinical recommendations challenging. Objective To report the extent, scope and nature of the existing literature on the use of SI during ETS and to identify research gaps. Data sources A systematic search was conducted of the following databases: ‘EMBASE’, ‘MEDLINE’, ‘Pedro’, ‘Cochrane’, ‘EMCARE’, ‘PubMed’ and ‘CINAHL’. Study selection Inclusion criteria: primary research, reporting on SI use during ETS on critical care, published in English between January 2013 and October 2025. Synthesis methods A charting form was developed and piloted to extract: Author, study demographics and design; aim; sampling technique/sample size; population; eligibility criteria; control/intervention; outcome measures and results. Results Ten studies were included. Five were interventional, primarily focusing on the effects of SI on patient physiological outcomes; only one conducted sputum analysis. Five studies were observational and explored ICU clinicians’ beliefs and perceptions surrounding SI use, most commonly justified in the context of managing thick or viscous secretions. Limitations Non-English language, review articles and grey literature were excluded. Conclusions There is limited contemporary research investigating the effects of SI during ETS. Literature remains heterogenous with a gap in primary research objectively looking at the efficacy of SI during ETS on secretion clearance i.e., secretion yield, the primary reason ICU clinicians utilise SI, highlighting a future research opportunity
Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids:REACT trial protocol
Get PDFIntroduction: Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.Methods and analysis: REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.Ethics and dissemination: The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number: ISRCTN18217497
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