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Without the ability to effectively recognise pain and assess its severity in animals, there is no way of assessing the efficacy of analgesia administered. Therefore, we have no way of ensuring that pain is adequately managed. Despite the extensive use of rodents in medical research that often involves the assessment of pain and distress, translation of this knowledge to veterinary medicine has been relatively neglected, and original veterinary research in pain assessment in rodents is lacking. This article aims to provide a broad overview of common behaviours that could be used to assess pain in rodents. [ABSTRACT FROM AUTHOR]

Competing Interests: CJAD reports grant funding and a Clinician Scientist Fellowship from the UK Medical Research Council (MR/X001598/1); acting on behalf of Newcastle upon Tyne Hospitals National Health Service Foundation Trust as an investigator on clinical trials funded or sponsored by manufacturers of vaccines and antimicrobials, including Moderna, AstraZeneca, Synairgen, Janssen, and Valneva, with no renumeration; remuneration for provision of consultative advice to Synairgen on behalf of Newcastle University; and serving on data safety and monitoring boards for non-commercial clinical trials sponsored by academic institutions, with no renumeration.

Agricultural activities are essential for sustaining the global population, yet they exert considerable pressure on the environment. A major challenge we face today is agricultural pollution, much of which is diffuse in nature, lacking a clear point of origin for chemical discharge. Modern agricultural practices, which often depend on substantial applications of fertilizers, pesticides, and irrigation water, are key contributors to this form of pollution. These activities lead to downstream contamination through mechanisms such as surface runoff, leaching, soil erosion, wind dispersal, and sedimentation. The environmental and human health consequences of diffuse pollution are profound and cannot be ignored. Accurate assessment of the risks posed by agricultural pollutants is crucial for ensuring the production of safe, high-quality food while safeguarding the environment. This requires systematic monitoring and evaluation of agricultural practices, including soil testing and nutrient management. Furthermore, the development and implementation of best management practices (BMPs) are critical in reducing the levels of agricultural pollution. Such measures are essential for mitigating the negative impacts on ecosystems and public health. Therefore, the adoption of preventive strategies aimed at minimizing pollution and its associated risks is highly recommended to ensure long-term environmental sustainability and human well-being., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice., Methods: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression., Results: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS., Conclusions: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke., Competing Interests: Competing interests: DSL reports having received grant funding from NINDS and consulting fees as an imaging core laboratory from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. RJ reports consulting with Phenox Medical, Microvention Terumo, and RapidPulse Inc. CBLMM reports having received grant funding from the CVON/Dutch Heart Foundation, Healthcare Evaluation Netherlands, European Commission, TWIN Foundation, and unrestricted grants from Stryker and Boehringer Ingelheim (all paid to institution) and is shareholder of Nicolab (minority interest). AvdL reports consulting fees from Stryker and grant funding from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Top Medical/Concentric, and Stryker, received by the Erasmus University Medical Center. LSR serves on a Data and Safety Monitoring Board (DSMB) for somatosensory evoked potentials (SEP) monitoring in patients with acute ischemic stroke and large anterior vessel occlusion undergoing endovascular thrombectomy. A clinical validation of the Brain20® medical device, Promise20. AD reports grants from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health and unrestricted grants from Penumbra Inc., Stryker, Medtronic, and Thrombolytic Science, all for research. JLS reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson & Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical. PJM reports unrestricted institutional scientific grants from Stryker and Medtronic. KWM reports consultancies with Boehringer Ingelheim, Biogen, Hyperfine, and lecture fees from Boehringer Ingelheim, IschemaView, and Brainomix. PW discloses institutional research grant support within the last 2 years from Microvention Terumo. He declares the following relevant professional relationships: Chair of the European Society of Minimally Invasive Neurotherapeutics Guidelines Committee, sits on the Policy Working Group for Thrombectomy of NHS England, and represents the Royal College of Radiologists on the UK Intercollegiate Stroke Working party - none of these are associated with financial reimbursement. He reports the following modest consultancy work: member of Stryker’s Global Hemorrhagic Stroke Advisory Board and educational consultancy work for Microvention Terumo. He has no other interests to declare. MG reports being the principal investigator of an unrestricted research grant to the University of Calgary for the HERMES collaboration by Medtronic. He also reports consulting services with Medtronic, Stryker, Microvention, and Cerenovus, and a licensing agreement with GE Healthcare regarding systems of acute stroke diagnosis., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Faecal Immunochemical Testing (FIT) is now core to the management of patients presenting in primary care with symptoms of possible colorectal cancer. Patients with a positive FIT (≥10μg Hb/g faeces) qualify for an urgent suspected cancer referral. FIT negative patients are typically managed in primary care or referred through routine pathways., Aim: To examine practitioners' experiences of delivering symptomatic FIT, identifying perceived benefits, disbenefits and implementation issues, to inform potential future service improvements., Design and Setting: Qualitative interview study with primary and secondary care health professionals, from across the UK, involved in delivering symptomatic FIT pathways., Method: 30 semi-structured interviews with professionals from a range of specialties. An iterative topic guide informed interviews while allowing freedom to explore novel lines of inquiry. Pseudo-anonymised transcripts were coded and themes identified and developed., Results: Symptomatic FIT was seen to be beneficial for increasing confidence in clinical decision-making and enriching the pool of patients being definitively investigated for colorectal neoplasia. There were varying views on the impact of symptomatic FIT on workload with the burden of additional workload generally seen to be located in primary care. Concerns about current practice included over-use of FIT, burden of investigations in patients with false-positive results and diagnostic delays, for both cancer and benign disease. Uncertainties existed around management of patients with rectal bleeding, appropriate strategies for safety-netting, and the value of repeat FIT., Conclusion: Symptomatic FIT is largely seen as beneficial; however, health professionals would welcome further evidence and guidance around optimal application., (Copyright © 2025, The Authors.)

Introduction: Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification., Methods: We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRS no APOE ), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls., Results: Together AD-PRS no APOE and APOE-RS performed similarly to p-tau181 in discriminating MCI+/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, Aβ positivity was significantly associated with APOE-RS, but not with AD-PRS no APOE , or p-tau181. Combining AD-PRS no APOE , APOE-RS, and p-tau181 improved the discrimination of MCI+/AD from controls (81%) and LBD (75%), and the detection of Aβ in LBD (82%)., Discussion: Aβ deposition in LBD was associated with APOE, while MCI+/AD was also associated with AD-PRS beyond APOE. AD-PRS explains phenotypic variance not captured by APOE or p-tau181., Highlights: We investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (APOE), and plasma phosphorylated tau 181 (p-tau181) to classify AD and Lewy body dementia (LBD). AD-PRS with APOE achieved similar classification accuracy to p-tau181. AD-PRS without APOE significantly contributed to discriminating AD from LBD. Amyloid beta positivity in LBD was associated with APOE but not AD-PRS without APOE or p-tau181. Combining AD-PRS, APOE, and p-tau181 improved diagnostic classification accuracy., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: This study aimed to assess the presence of spin in abstracts of systematic reviews and meta-analyses comparing biceps tenodesis and tenotomy outcomes and to explore associations between spin and specific study characteristics., Methods: Using Web of Science and PubMed databases, systematic reviews and meta-analyses comparing outcomes of biceps tenodesis and tenotomy were identified. Abstracts were evaluated for the nine most severe types of spin as described by Yavchitz et al. and appraised using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). Study characteristics were extracted, including adherence to PRISMA guidelines,funding status, and impact metrics such as journal impact factor, total number of citations, and average annual citations., Results: A total of 16 studies were included, with spin detected in 81.3% of the abstracts. Type three spin was the most frequent (56.3%), followed by types six (43.8%), five (37.5%), nine (25.0%), two (12.5%), and four (6.3%). Spin types one, seven, and eight were not observed. AMSTAR 2 appraised 75% of the studies as 'low' quality, and 25% as 'critically low' quality. All studies had at least one critical flaw, with item 15 (investigation of publication bias) being the most frequent (93.8%). A strong positive correlation was found between AMSTAR 2 scores and citation counts (r = 0.821, p < 0.001). Studies with a higher number of spin incidents were significantly more likely to have an associated letter to the editor (p = 0.0043)., Conclusion: Severe types of spin were prevalent in the abstracts of systematic reviews and meta-analyses comparing biceps tenodesis and tenotomy. Data analysis suggests that abstracts with a higher incidence of spin tend to attract more scrutiny from the academic community. These findings highlight the need to enhance reporting standards., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s) under exclusive licence to SICOT aisbl.)

Background and Rationale: In-stent restenosis (ISR) remains the leading cause of treatment failure following percutaneous coronary intervention (PCI) with contemporary drug-eluting stents. Especially in small caliber coronary arteries, restenosis is common following PCI and represents a treatment challenge. Drug-coated balloons (DCB) are an attractive alternative to stents for treatment of both ISR and small vessel disease. The safety and efficacy of the Prevail DCB will be assessed for (1) the treatment of ISR and (2) de novo lesions in small vessels., Trial Design: Prevail Global is a prospective, international, dual cohort clinical study enrolling (1) patients undergoing PCI for ISR in a randomized controlled trial (1:1) design comparing the Prevail DCB versus an FDA-approved DCB (Agent TM , Boston Scientific Corporation, Natick MA), and (2) patients with de novo small vessel disease undergoing PCI with the Prevail DCB as part of a single-arm study compared with a historical control. The primary endpoint is target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, or clinically-driven target lesion revascularization at 12 months post procedure. Patient follow-up is planned for 1 month, 6 months, and yearly through 5 years. Enrollment is expected to start in early 2025., Conclusions: The Prevail Global study will directly assess the safety and efficacy of the Prevail DCB for the treatment of ISR and de novo small vessel lesions., Trial Registration: Prevail Global, NCT06535854, is registered at https://clinicaltrials.gov/study/NCT06535854., Competing Interests: Declaration of competing interest Dr. Kandzari reports institutional research and grant support from Ablative Solutions, Biotronik, Orbus Neich, Medtronic and Teleflex; and personal consulting honoraria from Ablative Solutions, Medtronic, Amplitude Vascular Systems and Orchestra Biomedical. Dr Latib has served as a consultant and/or advisory board member for Edwards Lifesciences, Abbott, Medtronic, Boston Scientific, Shifamed, NeoChord, VDyne, and Philips. Dr. Mylotte is a consultant for Medtronic, Boston Scientific, and Microport and has received institutional research grants from Medtronic and Boston Scientific. Dr. Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, Cathworks, Canon, Conavi, Chiesi, Heartflow, Inari, Medtronic, the National Institute of Health, Nipro, Opsens Medical, Medis, Philips, Schockwave, Siemens, Spectrwave, and Teleflex. Dr. Ali receives consultant fees from Abiomed, Astra Zeneca, Boston Scientific, Cathworks, Heartflow, Opsens, Philips, and Shockwave. Dr. Ali has equity in Elucid, Lifelink, Spectrawave, Shockwave, and VitalConnect. Dr. Zaman does not have conflicts of interest to declare. Dr. Brar and Mrs. Parke are employees of Medtronic. Dr. Scheller report is a shareholder of InnoRa GmbH (Berlin, Germany) and has received lecture fees from B. Braun and Medtronic., (Copyright © 2025. Published by Elsevier Inc.)

Acid mine drainage (AMD) is a worldwide problem that degrades river systems and is difficult and expensive to remediate. To protect affected catchments, it is vital to understand the behaviour of AMD-related metal(loid) contaminants as a function of space and time. To address this, the sources, loads and transport mechanisms of arsenic (As), copper (Cu), zinc (Zn), iron (Fe) and sulfur (S) in a representative AMD-affected catchment (the Carnon River in Cornwall, UK) were determined over a 12-month sampling period and with 22 years of monitoring data collected by the Environment Agency (England) (EA). The main source of metal(loid)s to the Carnon River was the County Adit which drains AMD from approximately 60 km of underground historical mine workings. Maximum aqueous concentrations of Fe, Cu and Zn occurred immediately downstream of the County Adit confluence with the Carnon River, whereas maximum As and S concentrations occurred further downstream, suggesting the presence of diffuse sources. Discharge and concentration relationships suggested that discharge drove Cu and Zn release, whereas pH and Eh influenced Fe, S, and As mobility. Total loads (represented by unfiltered sample contaminant concentrations) to the coastal zone were high, ranging from 183 to 354 kg/month As, 307-742 kg/month Cu, 189-1960 kg/month Fe, 53,400-125,000 kg/month S and 1280-3320 kg/month Zn. The longevity and increasing amounts of contaminant discharge were confirmed with 22 years of EA monitoring data. This study highlights the complex and multifaceted behaviour of contaminant metal(loid)s within AMD-affected riverine systems and the fact that point and diffuse sources can constitute significant long-term liabilities for such environments., Competing Interests: Declaration of competing interest The authors affirm that no apparent financial conflicts of interest or personal associations could have conceivably influenced the findings presented in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Significant progress has been made in elucidating the genetic underpinnings of Autism Spectrum Disorder (ASD). However, there are still significant gaps in our understanding of the link between genomics, neurobiology and clinical phenotype in scientific discovery. New models are therefore needed to address these gaps. Rhesus macaques (Macaca mulatta) have been extensively used for preclinical neurobiological research because of remarkable similarities to humans across biology and behaviour that cannot be captured by other experimental animals., Methods: We used the macaque Genotype and Phenotype (mGAP) resource consisting of 2,054 macaque genomes to examine patterns of evolutionary constraint in known human neurodevelopmental genes. Residual variation intolerance scores (RVIS) were calculated for all annotated autosomal genes (N = 18,168) and Gene Set Enrichment Analysis (GSEA) was used to examine patterns of constraint across ASD genes and related neurodevelopmental genes., Results: We demonstrated that patterns of constraint across autosomal genes are correlated in humans and macaques, and that ASD-associated genes exhibit significant constraint in macaques (p = 9.4 × 10 - 27 ). Among macaques, many key ASD-implicated genes were observed to harbour predicted damaging mutations. A small number of key ASD-implicated genes that are highly intolerant to mutation in humans, however, showed no evidence of similar intolerance in macaques (CACNA1D, MBD5, AUTS2 and NRXN1). Constraint was also observed across genes associated with intellectual disability (p = 1.1 × 10 - 46 ), epilepsy (p = 2.1 × 10 - 33 ) and schizophrenia (p = 4.2 × 10 - 45 ), and for an overlapping neurodevelopmental gene set (p = 4.0 × 10 - 10 )., Limitations: The lack of behavioural phenotypes among the macaques whose genotypes were studied means that we are unable to further investigate whether genetic variants have similar phenotypic consequences among nonhuman primates., Conclusion: The presence of pathological mutations in ASD genes among macaques, along with evidence of similar genetic constraints to those in humans, provides a strong rationale for further investigation of genotype-phenotype relationships in macaques. This highlights the importance of developing primate models of ASD to elucidate the neurobiological underpinnings and advance approaches for precision medicine and therapeutic interventions., Competing Interests: Declarations. Ethics approval and consent to participate: All data collection for mGAP database protocols adhered to the NIH and the Guide for Use and Care of Laboratory Animals and were approved by the Oregon Health & Sciences University Animal Utilization and Care Committee [22]. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: One in five sebaceous tumour (ST) patients may have Lynch syndrome (LS), a hereditary cancer predisposition. LS patients benefit from cancer surveillance and prevention programmes and immunotherapy. Whilst universal tumour mismatch repair (MMR) deficiency testing is recommended in colorectal and endometrial cancers to screen for LS, there is no consensus screening strategy for ST, leading to low testing rates and inequity of care., Objectives: To assess a low cost and scalable, sequencing-based, microsatellite instability (MSI) assay, previously shown to enhance LS screening of colorectal cancers, for MMR deficiency detection in ST against the current clinical standard of immunohistochemistry (IHC)., Methods: One-hundred-and-seven consecutive ST cases were identified from a single pathology department. MMR protein IHC staining was interpreted by a consultant histopathologist. MSI analysis used amplicon-sequencing of 14 microsatellites and a naïve Bayesian classifier to calculate sample MSI score., Results: Loss of MMR protein expression was observed in 49/104 ST with interpretable IHC (47.1%; 95% CI: 37.3-57.2%). MMR deficiency was less frequent in carcinoma than adenoma and sebaceoma (P = 4.74x10-3). The majority of MMR deficient ST had concurrent loss of MSH2 and MSH6 expression. The MSI score achieved a receiver operator characteristic area under curve of 0.944 relative to IHC. Lower MSI scores were associated with MSH6 deficiency., Conclusions: These data support MSI testing as an adjunct or alternative to MMR IHC in ST. Integration of ST into established LS screening pathways using this high throughput methodology could increase testing and reduce costs., (© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.)

A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD. A literature review was performed and extended to a meta-analysis when possible. For this purpose, PubMed and EMBASE were searched up to May 2024. Fifty-four publications, describing a total of 2391 procedures, were included. In addition, an exploratory questionnaire was sent to urologists, nephrologists, and transplant-surgeons. These sources were used to develop practice points about indications, complications, mortality, timing, and technique of nephrectomy. In addition, data on renal embolization as a potential alternative to nephrectomy was explored and summarized. To reach consensus, practice points were defined and improved in three Delphi survey rounds by experts of the European Renal Association Working Group Genes & Kidney and the European Association of Urology Section of Transplantation Urology. A total of 23 practice points/statements were developed, all of which reached consensus. Among others, it was deemed that nephrectomy can be performed successfully for various indications and is an intermediate risk procedure with acceptable mortality and minimal impact on kidney graft function when performed before, in the same session or after transplantation. The complication rate seems to increase when the procedure is performed as an emergency. During the work-up for transplantation, patient complaints should be assessed routinely by questionnaires to indicate symptom burden. Deciding on the need for nephrectomy and exploring potential alternatives such as kidney embolization should be a process of shared decision making, preferably after multidisciplinary consultation., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path&#95;APC) and pathogenic mismatch repair gene (path&#95;MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path&#95;APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years. In path&#95;MLH1 and path&#95;MSH2 carriers, second hits lead to the formation of microscopically detectable, microsatellite unstable (MSI) crypts, from which CRC develops in about half of carriers over their lifetime, often without progressing through a diagnosable adenoma stage. These divergent outcomes reflect the distinct functions of. the APC and MMR genes. In path&#95;MLH1 and path&#95;MSH2 carriers, a direct consequence of stochastic mutations may be the occurrence of invasive growth before tumour expansion, challenging the paradigm that an invasive cancer must always have an non-invasive precursor. In contrast to other path&#95; MMR carriers, path&#95;PMS2 carriers who receive colonoscopic surveillance exhibit minimal increase in CRC incidence. This is consistent with a hybrid model: the initial mutation may cause an adenoma, and the second hit in the wild-type PMS2 allele may drive the adenoma towards become cancerous with MSI. Since all mutational events are stochastic, interventions aimed at preventing or curing cancer should ideally target the initial mutational events. Interventions focused on downstream events are external factors that influence which tumour clones survive Darwinian selection. In Lynch Syndrome, surveillance colonoscopy to remove adenomas may select for carcinogenetic pathways that bypass the adenoma stage., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Informed consent: Not applicable. Competing interests: T.T.S. reports consultation fees from Mehiläinen, Nouscom, Orion Pharma, Amgen, and Tillots Pharma, being a co-owner and CEO of Healthfund Finland Ltd., and a position in the Clinical Advisory Board and as a minor shareholder of Lynsight Ltd. M.D.V. is advisor of Nouscom. Other authors declare that they have no conflicts of interest. All other authours declare no conflict of interest relevant to the current paper., (© 2025. The Author(s).)

Background: There is limited literature in paediatric rheumatology describing holistic lived experiences of medical treatment from perspectives of children and young people (CYP) and their parents or carers (PC). This is important as it could have implications for adherence. This study aimed to explore treatment experiences of CYP and PC in a paediatric rheumatology service., Methods: Participants were recruited at a day-case unit for intravenous infusions at a tertiary paediatric rheumatology centre. Joint qualitative semi-structured interviews with CYP and PC were used to collect data. Data were transcribed, quality checked and thematically analysed using NVivo 12.4 to identify findings., Results: Thirty-two participants (15 CYP between the ages of 6 and 16 years, 17 PC) took part in interviews lasting 41 min and 43 s, on average. Participants described experiences using infliximab, followed by tocilizumab and abatacept. Participants experienced a wave, oscillating between positive and negative trajectories. Experiences of medical treatments were described as temporary, eventually changing and leading to treatment changes or cessation. Behaviours were influenced through somatic factors (pain, function), social factors (advice from health professionals, encouragement from friends, family and teachers, practicality of using treatment in relation to school, work and finance) and cognitive factors (fear of needles, fear of specific medications, beliefs about necessity)., Conclusions: Collectively, findings demonstrate experiences of medical treatment reflect the nature of many paediatric rheumatology conditions, oscillating between periods of positive and negative trajectories. Somatic, social and cognitive experiences can be positive, when treatment is considered 'successful'. Negative somatic, social or cognitive experiences led to behaviours such as treatment non-adherence. A limitation of the study is interviews were conducted jointly with CYP and PC, which may have influenced what participants were willing to say in front of one another however this does mean findings relate to both CYP and PC and so could be suitable targets for interventions to improve adherence., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the study was given the Faculty of Medical Sciences Research Ethics Committee (Reference number 33823/2023) and the project was registered on the Trust’s Clinical Effectiveness Register. Consent for publication: We confirm that all authors have approved the manuscript for submission. Also, I, Adam Pattison Rathbone, confirm that the manuscript has not been published, and have not been submitted for publication elsewhere. Competing interests: The authors declare they have no competing interests. Author information: KGP was an MRes student working under the supervision of SS and APR. SS is a Paediatric Rheumatology Consultant in at the Great North Children’s Hospital, AM is a Reader in Pharmacy Practice at Liverpool John Moore’s Hospital, CLR is a Senior Lecturer in Pharmacy Practice at Newcastle University, and APR is a Lecturer in Clinical and Social Pharmacy at Newcastle University and Advanced Clinical Pharmacist at the Children’s Hospital., (© 2025. The Author(s).)

Aim: This paper aims to explore the significance of umbrella reviews as a methodological advancement in evidence synthesis, emphasizing their role in aggregating data from multiple systematic reviews and their impact on evidence-based practice and policy-making., Methods and Results: The paper examines the evolution of systematic reviews and meta-analyses, highlighting the emergence of umbrella reviews as a comprehensive synthesis method. It details the key steps involved in conducting an umbrella review, including literature searches, study selection, quality appraisal, and data synthesis. Various types of umbrella reviews are discussed, along with the integration of advanced methodologies and interdisciplinary approaches that enhance their effectiveness., Conclusion: Umbrella reviews have become an essential tool in evidence synthesis, offering a higher-level aggregation of systematic reviews to inform decision-making in clinical and policy contexts. Their evolving methodologies, combined with interdisciplinary approaches, make them crucial in shaping the future of evidence-based practice globally., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Semitic languages such as Hebrew and Arabic are known for having a non-concatenative morphology: words are typically built of a combination of a consonantal root, typically tri-consonantal (e.g., k-t-b "related to writing" in Modern Standard Arabic (MSA)), with a prosodic template. Research on Hebrew language development suggests early sensitivity to frequently occurring templates. For the Arabic dialects, little is known about whether implicit sensitivity to non-concatenative morphology develops at a young age through exposure to speech, and how templatic the spoken language is in comparison to MSA. We focus on Lebanese Arabic. We hypothesized that prolonged contact with French and English may have "diluted" the salience of roots and patterns in the input. We used three different corpora of adult-directed-speech (ADS), child-directed-speech (CDS), and child speech. We analyzed the root and pattern structures in the 50 most frequent Lebanese Arabic word types in each corpus. We found fewer words with templatic patterns than expected among the most frequent words in ADS (35/50), even fewer in CDS (23/50) and still fewer in the children's target words (15/50). In addition, only a minority contains three root consonants in their surface forms: 22 in ADS, 15 in CDS, and only 7 in words targeted by the children. We conclude that Semitic structure is less evident in either input to children or words targeted by children aged 1-3 than has been assumed. We discuss implications for the development of sensitivity to templatic structure among Lebanese-acquiring children.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are more prevalent in males than females. Furthermore, they typically showed abnormally high delta (< 4 Hz) and low alpha (8-10 Hz) rhythms from resting-state electroencephalographic (rsEEG) activity. Here, we hypothesized that those abnormalities may depend on the patient's sex. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 49; 24 females), PDD (N = 39; 13 females), and DLB (N = 38; 15 females) participants. Each group was stratified into matched female and male subgroups. The rsEEG rhythms were investigated across the individual rsEEG delta, theta, and alpha frequency bands based on the individual alpha frequency peak. The eLORETA freeware was used to estimate cortical rsEEG sources. In the Healthy group, widespread rsEEG alpha source activities were greater in the females than in the males. In the PDD group, widespread rsEEG delta source activities were lower and widespread rsEEG alpha source activities were greater in the females than in the males. In the DLB group, central-parietal rsEEG delta source activities were lower, and posterior rsEEG alpha source activities were greater in the females than in the males. These results suggest sex-dependent hormonal modulation of neuroprotective-compensatory neurophysiological mechanisms in PDD and DLB patients underlying the generation of rsEEG delta and alpha rhythms, which should be considered in the treatment of vigilance dysregulation in those patients., Competing Interests: Declaration of competing interest, (Copyright © 2025. Published by Elsevier Inc.)

Background and Objective: Stress urinary incontinence (SUI), defined as any involuntary leakage of urine associated with physical activity, remains underdiagnosed and undertreated. This review aims to provide an updated overview of the prevalence, diagnosis, and treatment of SUI in women, drawing upon recent evidence-based literature and clinical guidelines., Methods: A systematic search of the MEDLINE database was conducted to identify only the most up-to-date and relevant studies published up to February 26, 2024, including the reference ESTER systematic review. The search was limited to systematic reviews published in the preceding 1 yr. Any additional included publications were limited to those published or referenced as part of the existing/current guidelines., Key Findings and Limitations: Diagnosis of SUI involves a comprehensive assessment, including medical history, physical examination, and in some cases, invasive urodynamics. Pelvic floor muscle training emerges as a first-line management strategy, showing efficacy in symptom improvement when good educational instructions and supervision are provided. Surgical interventions with midurethral and single-incision slings offer a second-line option, although concerns regarding mesh-related complications persist with a decrease in its use. Moreover, the long-term efficacy of single-incision slings remains to be confirmed. Urethral bulking agents, colposuspension, and autologous fascial slings are existing alternatives supported by robust evidence, albeit with a different adverse event profile. Management of complicated and severe SUI remains challenging, with autologous fascial sling and artificial urinary sphincters being established treatments, but high-quality data remain lacking., Conclusions and Clinical Implications: Heightened awareness and accessibility to SUI treatment are imperative to address the gap between prevalence and medical care-seeking behavior. Pelvic floor muscle training and surgical interventions represent key modalities. However, a notable escalation in invasiveness and complication rates when transitioning to surgical interventions is clear and has resulted in a hesitance among patients to proceed along the treatment continuum, particularly in light of mesh-related complications. Ongoing research is necessary to optimize outcomes and ensure patient safety, particularly for complicated SUI where data on comparative effectiveness remain limited., (Copyright © 2025 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Previous literature has highlighted the complexity of supporting an acutely unwell child and the unnecessary use of services by parents/carers. The Little Orange Book (LOB) was developed as an information resource for parents/carers of young children to assist in managing symptoms of childhood illness and to encourage the appropriate use of healthcare services., Objectives: This study aimed to understand parent/carer views and experiences using the Little Orange Book. Specifically, this study focused on barriers and facilitators to use, the impact on parents' behaviour and the views on improving the LOB., Methods: An explanatory sequential mixed-methods approach, including qualitative and quantitative components, was used to collect data regarding parent's experiences using the LOB. Parents and carers in the North-East of England were invited to participate in an online survey and a subset of these respondents took part in qualitative interviews. One-hundred-and-twenty-eight parents completed the online survey and 16 took part in interviews. Qualitative data were analysed using thematic analysis and quantitative data analysed using descriptive statistical analytical methods., Results: Three themes were identified within the data: Increasing parental empowerment in managing their child's health, Equality of Access to Health-based Literature and Barriers and Facilitators to using the Little Orange Book., Conclusions: The Little Orange Book was seen as a valuable form of information to support parents and carers in healthcare decisions. Further development should ensure inclusivity, widen access and view provision of the information as an opportunity for healthcare professionals to engage with parents., Competing Interests: No authors have competing interests, (Copyright: © 2025 Johnson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)