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Enabling people to reduce their consumption of unhealthy appetitive products can improve their health. Over the last decades, progress has been made by uncovering new ways to change behavior toward appetitive products without feedback incentives (e.g., reward or punishment, as in feedback-driven reinforcement learning), but instead by cueing motor responses (e.g., go vs. no go) toward these products in cognitive training tasks. However, it is unclear how this nonreinforced learning compares to reinforcement learning. Moreover, recent work on reinforcement learning has uncovered a basic learning mechanism, the action-valence asymmetry, which points to the possibility that reward and punishment learning may not always outperform learning without any external reinforcement. Here, we report two well-powered preregistered experiments (experiment 1a: N = 72; experiment 1b: N = 81) that examined when reinforcement learning outperforms nonreinforced learning in modifying people's preferences for food. Our findings show that reinforcement learning notably surpasses nonreinforced learning, but only when active responses (go) are rewarded, and inactions (no-go) are reinforced by avoiding punishments. These results shed light on interventions that combine rewards and punishments to facilitate changes in food preferences., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the author(s). All authors declare no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Spatial pain patterns are widely used as diagnostic tools, yet population-level estimates, such as the prevalence of pain in specific body regions and likelihood of their co-occurrence, are lacking. Despite this, bilateral limb pain is considered relatively uncommon. Baseline data from a population-based Danish cohort were analysed. Twenty-one pain drawing regions, coded as binary "pain"/"no-pain" variables, were entered into an Ising model. Conditional dependencies between pairs of painful regions were quantified, while accounting for the pain state of other regions. Four-week prevalence of pain was also calculated for body regions. Of 4833 analysed pain drawings, 34.7% (1676) reported bilateral (upper or lower) limb pain and 32.3% (1561) reported symmetrical (mirrored) bilateral limb pain. Strongest positive edge weights of the Ising model were between mirrored contralateral regions; the strongest being between left and right hips (mean: 3.86, 95% confidence interval: 3.84-3.87). Next strongest edge weights were between spatially adjacent ipsilateral regions; the strongest being between the right hip and right buttock (mean: 2.72, 95% confidence interval: 2.71-2.74). Negative edge weights, indicating inhibitory relationships, were consistently seen between nonmirrored contralateral regions, the strongest being between regions adjacent to their mirrored contralateral counterparts. In conclusion, bilateral limb pain, particularly in mirrored regions, is more prevalent than previously thought. Pain co-occurrence is facilitated between mirrored contralateral regions and, to a lesser degree, between adjacent ipsilateral regions. An inhibitory effect occurs between nonmirrored contralateral regions, diminishing with increasing distance from the mirrored region. Potential inhibition between mirrored contralateral regions is likely overshadowed by the more dominant facilitation., (Copyright © 2025 International Association for the Study of Pain.)

Background & Aims: Head and Neck Cancers (HNCs) pose a significant global health burden, with increasing incidence projected by 2030. Treatment typically involves radiotherapy (RT) and chemoradiotherapy (CMRT), often leading to debilitating oral mucositis (OM) causing impaired quality of life and sometimes inability to continue treatment. Currently, there are no established preventive and therapeutic measures for OM in HNC patients. This systematic review aims to consolidate available evidence on the efficacy of zinc supplementation in mitigating the onset, duration, and severity of OM during RT and CMRT in HNC patients., Methods: We searched the Medline, Embase, and Web of Science databases for all records of HNC patients who were getting RT or CMRT and different kinds of zinc supplements from January 2013 to July 2023. Search terms included various HNC, RT, chemoradiotherapy, and zinc supplementation permutations. Only interventional studies were included, with quality assessment conducted using the JBI risk of bias tools. Findings were synthesized narratively., Results: Eight studies involving 651 HNC patients, comprising six randomized controlled trials (RCTs) and two non-randomized controlled trials, were included. Various radiotherapy techniques and concurrent chemotherapy were utilized across studies, with zinc administered in multiple forms including syrup, tablets, suspension, topical application, and mouthwashes. Overall, six studies reported a beneficial effect of zinc supplementation in reducing the incidence, onset, duration, and severity of OM, while two studies reported no significant impact., Conclusion: Zinc supplementation shows promise in ameliorating OM in HNC patients undergoing RT and chemoradiotherapy, likely due to its antioxidative, anti-inflammatory, and wound healing properties. Further research is warranted to elucidate optimal dosage and regimen for zinc supplementation in this context., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with hypertrophic cardiomyopathy, the prognostic value of myocardial T1 and extracellular volume fraction for adverse cardiovascular events has not been well defined., Methods: A total of 663 consecutive participants with hypertrophic cardiomyopathy who underwent 3T cardiovascular magnetic resonance were recruited. The follow-up end points included heart failure (HF)-related death, HF hospitalization, and sudden cardiac death or aborted sudden cardiac death., Results: On Cox proportional hazards regression multivariable analyses, global native T1 excluding late gadolinium enhancement areas (hazard ratio [HR], 1.04 [95% CI, 0.99-1.09]; P =0.094) and global extracellular volume fraction excluding late gadolinium enhancement (HR, 1.02 [95% CI, 0.95-1.10]; P =0.565) were not associated with sudden cardiac death. Conversely, global native T1 (HR, 1.08 per 10 ms increase [95% CI, 1.02-1.16], P =0.014; HR, 1.05 per 10 ms increase [95% CI, 1.01-1.09]; P =0.009) and global extracellular volume fraction (HR, 1.23 per 1% increase [95% CI, 1.11-1.36], P <0.001; HR, 1.10 per 1% increase [95% CI, 1.04-1.16]; P <0.001) were independently associated with HF-related death and the composite end point of HF-related death or HF hospitalization in multivariable Cox models, respectively., Conclusions: In this study of patients with hypertrophic cardiomyopathy, we found global native T1 and global extracellular volume fraction (excluding late gadolinium enhancement) to be both independently associated with HF-related events, but not sudden cardiac death in multivariable analysis. These findings are hypothesis-generating and will require external validation in larger cohorts., Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900024094.

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease affecting mainly the joints, often with extra articular manifestations. This review provides an update on RA epidemiological trends and management. PubMed and EMBASE were searched from 2014 to 2024 using rheumatoid arthritis as keyword, combined with incidence, prevalence, diagnosis, classification, and management. Emphasis was on papers published in the past 5 years. Globally, the age-standardised prevalence and incidence rate (ASPR and ASIR) of RA increased with varying figures. The ASPR increased by 0.37%, 14.1%, and 6.4% from 1990 to 2019, 2020 and 2017 respectively; and 9% from 1980 to 2019. The ASIR increased by 0.3% and 8.2% from 1990 to 2019 and 2017 respectively; the disability-adjusted life years (DALY) figures increased 0.12% and decreased 0.36% in the same period from different authors. Reduction in ASIR were reported while ASPR varies. Disease modifying anti-rheumatic drugs (DMARDs) remain the cornerstone of treatment., 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. Published by Elsevier Ltd.)

Objectives: Human papillomavirus (HPV) mediated oropharyngeal cancer (OPC) incidence has increased dramatically. Accurate oral HPV prevalence data are essential for assessing population epidemiology, vaccination and screening programmes. As oral rinse is the most commonly used primary outcome measure for estimating oral HPV prevalence, we aimed to compare the efficacy of oral rinse against other detection methods., Methods: The Oromouth study enrolled 945 participants, aged 0-65 years (63% female), undergoing tonsillectomy for non-malignant indications, without OPC diagnoses. Samples from oral rinse, pharyngeal wall, tongue base, tonsil tissue and blood were collected. HPV DNA in oral samples was centrally tested via polymerase chain reaction, and serology samples for HPV antibodies. Statistical analyses assessed prevalence, detection rates and ratios., Results: Combining all four oral collection sites, high-risk (HR)-HPV and any HPV prevalence were 4·3% and 18%, respectively. HR-HPV prevalence was similar between males (4·1%) and females (4·5%). Oral rinse had the highest HR-HPV (4·0%) and any HPV detection rates (16%), but still missed 73% (11/15) identified as HR-HPV-positive by other oral sites. Compared to oral rinse alone, an additional 38% (11/29) HR-HPV infections were picked up by the other three oral collection methods. Addition of serology testing did not result in substantial improvement., Conclusions: Of the four oral sites, oral rinse demonstrates the highest detection rates by far but has important limitations. These findings should be taken into consideration when estimating oral HPV infection rates, especially for vaccination studies and screening programmes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All other authors received no personal funding and have declared that no competing interests exist., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the variation and quality of the outcomes reported using descriptive analysis and interactive network visualisation of CS outcomes of comparative studies conducted in low-and middle-income settings., Study Design: Systematic review of comparative studies to reduce caesarean section complications in low- and middle-income countries and outcome assessment using the modified Harman questionnaire, assessing for the presence of a clear primary outcome, an explanation of how the outcomes were analysed and a description of the methods used to enhance the quality of these measures., Results: 102 comparative studies were included. Studies of interventions to improve maternal and perinatal outcomes after caesarean section reported 466 outcomes with 15 % of these outcomes appearing only once across the outcomes reviewed (n = 73). The most common outcome categories reported were maternal death, disability and bleeding. Psychological and injury outcomes were less commonly reported. The overall quality of outcome reporting varied between studies but was particularly low for reporting on methods to improve outcome measures. Very few outcomes scored a maximum of three points when assessed according to the modified Harman score, with only 15 of the primary outcomes (16 %) achieving 3 points and 40 of the secondary outcomes (11 %) achieving 3 points. The median quality of reporting was 2 (range 0, 3) for all outcomes, for a maximum score of 3. Quality of outcome reporting was associated with the type of outcome (primary or secondary), the region in which the study was conducted in, and journal characteristics such as impact factor and journal type., Conclusions: There was wide variability in both the outcomes reported and the frequency in which they were reported. Overall, very few primary and secondary outcomes achieved the maximum score of three on the modified Harman score, highlighting the need for a core outcome set for caesarean section intervention trials to improve the consistency and synergy of future research outcome definition, measurement and synthesis., Trial Registration: The protocol was registered (PROSPERO CRD42022353939)., 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. Published by Elsevier B.V.)

Background: Excessive supraventricular ectopic activity (ESVEA) is regarded as a risk marker for later atrial fibrillation (AF) detection., Methods and Results: The investigator-initiated, prospective, open, multicenter MonDAFIS (Impact of Standardized Monitoring for Detection of Atrial Fibrillation in Ischemic Stroke) study randomized 3465 patients with acute ischemic stroke without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter monitoring in hospital for up to 7 days, analyzed in a core laboratory. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding, and all-cause death within 24 months in patients with ESVEA (defined as ectopic supraventricular beats ≥480/day or atrial runs of 10-29 seconds or both) versus patients with newly diagnosed AF versus patients without ESVEA or AF (non-ESVEA/AF), randomized to the intervention group. Overall, 1435 (84.8%) of 1714 patients randomized to the intervention group had analyzable study ECG monitoring of at least 48 hours' duration within the first 72 hours of monitoring. ESVEA was detected in 363 (25.3%) patients, while AF was first detected in 48 (3.3%) patients. Within 24 months, AF was newly detected in 67 (18.5%) patients with ESVEA versus 60 (5.9%) patients without ESVEA/AF- ( P <0.001). The composite outcome at 24 months was not different between patients with ESVEA and patients without ESVEA/AF (15.2% versus 12.6%; P =0.242). All-cause death was numerically higher in patients with ESVEA (6.6% versus 3.2%), but failed statistical significance ( P =0.433) in multivariate analysis (including age, heart failure, stroke severity, and creatinine at baseline)., Conclusions: ESVEA in the acute phase of ischemic stroke or transient ischemic attack is associated with AF detection during follow-up and therefore may be used to select patients for prolonged ECG monitoring., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.

Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis., Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis., Design, Setting, and Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024., Intervention: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management., Main Outcomes and Measures: The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months., Results: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70])., Conclusions and Relevance: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT03094143.

Background: Asthma is the most common chronic disease in children, resulting in considerable morbidity and healthcare utilisation, especially in geographical areas with high deprivation. Parents play a pivotal role in children's asthma management., Aim: To explore the views of parents whose children have asthma, regarding barriers and facilitators to receiving adequate asthma care., Design & Setting: A qualitative study conducted in an urban, multi-ethnic setting with high socioeconomic deprivation and paediatric asthma-related hospital admissions., Method: The study used a pragmatic approach underpinned by a perspective of critical realism. Parents of children with asthma were recruited through purposive and convenience sampling, and data were collected through semi-structured interviews. Transcripts were analysed using thematic analysis, facilitated by NVivo12 software., Results: Ten parents participated in nine interviews. Six themes were identified relating to the following: (1) the establishment of a new life dynamic following a diagnosis of asthma; (2) the turbulent and drawn-out process of asthma diagnosis; (3) the roles and expectations of the partnership established between parents and healthcare services; (4) the importance of schools in asthma management; (5) sources and access to relevant information; and (6) the importance of social support networks. Parents frequently felt unsupported and misunderstood, particularly during the diagnostic process., Conclusion: Unmet parental educational and emotional needs, particularly around the time of diagnosis, were identified as a key barrier to adequate asthma management. Deeper understanding of gaps in support can instruct asthma care delivery and inform co-produced interventions, thus improving asthma outcomes in children., (Copyright © 2024, The Authors.)

Background: Understanding the risk of cancer after the diagnosis of another condition can present opportunities for earlier diagnosis. We examined the risk of cancer diagnosis conditional on prior diagnosis of atrial fibrillation (AF)., Methods: Linked electronic health records were used to identify patients aged ≥18 with new-onset AF and age-sex-matched controls. Cumulative incidence of and mortality from cancer (overall and cancer-site specific) within three months, three months to five years and beyond five years from diagnosis of AF were examined. Findings were further validated using Mendelian randomisation (MR)., Results: The cohort included 117,173 patients with new-onset AF and 117,173 matched controls (median age 78). In the first three months, 2.2% of AF patients were diagnosed with cancer vs. 0.47% in controls (relative risk: 4.7 [95%CI 4.2-5.4] in men and 4.4 [95%CI 3.8-5.0] in women). Nearly 80% of cancers related to thoracic or abdominal organs. Differences in cumulative incidence were only evident in women between three months and five years (subdistribution hazard ratio=1.1 [95%CI 1.01-1.12]) and absent in all patients beyond five years. MR analysis did not support the presence of a causal association between AF and major cancer subtypes., Conclusion: There is a large short-term increase in cancer incidence and mortality following new-onset AF. The findings may reflect incidental identification of AF or paraneoplastic manifestation. New-onset AF confers high short-term risk of cancer diagnosis, at levels comparable with symptomatic risk threshold mandating urgent assessment for suspected cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871., (Copyright © 2024. Published by Elsevier Inc.)

Aims: Tissue V12Gy (total brain volume receiving 12Gy including target) can predict for late toxicity in single target benign disease treated with stereotactic radiosurgery (SRS). The value of this metric remains uncertain for multiple brain metastases. This retrospective cohort study reports the outcomes and evaluates the predictors of toxicity in patients with four or more brain metastases treated with single-fraction SRS., Materials and Methods: Two hundred twenty-six patients with 2160 metastases treated from 2014-21 were retrospectively studied. Symptomatic late toxicity (new/progressive neurological symptoms ≥3 months post SRS) with magnetic resonance imaging (MRI) changes suggestive of treatment effect were analysed. Kaplan-Meier and competing risk analysis was used to assess survival and toxicity respectively., Results: median number of metastases/patient was 6 (range: 4-41) and median composite tissue V12Gy (inclusive of planning target volume (PTV)) was 11.3 cc (IQR: 6.1 cc-17.1 cc). Sixteen out of the 226 patients developed symptomatic late radiation adverse event (R-AE), and the cumulative incidence was 4.9% at 1 year and 6.9% at 2 years. The total target volume was significantly predictive of the risk of late R-AE. Volume of the largest lesion, V12Gy and V15Gy did not predict for late R-AE, but plotted graphs showed suggestions of linear relationships between dosimetric parameters and late R-AE., Conclusion: Within the limitations of this study, the cumulative incidence of symptomatic toxicity remains acceptable despite routinely accepting a composite tissue V12Gy in excess of 10 cc to treat multiple brain metastases., Advances in Knowledge: V12Gy has limitations as a plan quality metric in multiple brain metastases treated with SRS. There is insufficient evidence to have a defined target limit as <10 cc., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with Self-Reported Penicillin Allergy (SRPA) receive alternative antibiotics, which increase the length of stay and hospital costs, but the impact of SRPA on mortality in critically ill patients is not well described., Methods: This was a single-center, retrospective analysis of routinely gathered clinical data for all intensive care unit (ICU) admissions over nine years. The primary outcome was 28-day mortality, which was analyzed using a time-to-event approach with multivariable models to adjust for confounding factors, including age, comorbidities, sex, and admission SOFA score (as a measure of organ dysfunction). Antibiotic prescriptions during the ICU stay were also interrogated and compared., Results: Of 35,319 admissions, 11.7% had SRPA. Compared with non-SRPA, patients with SRPA were more likely to be female (52.2% vs. 37.4%, p < 0.001) and had more comorbidities (p < 0.001) but had similar admission SOFA scores (median: 3.5 in both groups, p = 0.839). Patients with SRPA had significantly lower 28-day mortality (9.6% vs. 10.9%, p = 0.011). After multivariable adjustment for baseline characteristics, this effect persisted for unplanned (hazard ratio [HR]: 0.76, 95% CI: 0.68-0.86, p < 0.001), but not planned admissions (HR: 1.21, 95% CI: 0.92-1.58, p = 0.172). Whilst the duration of antibiotics in ICU was similar in the SRPA and non-SRPA groups (mean: 3.4 vs. 3.4 days, p = 0.663), the antibiotics used differed, with SRPA patients being significantly more likely to receive quinolones or other anti-Gram-positive antibiotics (p < 0.001)., Conclusion: SRPA was associated with a survival benefit that persisted after adjustment for confounders for unplanned ICU admissions. Patients with SRPA were more likely to receive antibiotics that are not active against anaerobic bacteria., Competing Interests: Declaration of competing interest The authors declare no conflicting interests for this work., (Crown Copyright © 2024. Published by Elsevier Masson SAS. All rights reserved.)

The spike-based neuronal responses within the ventral intraparietal area (VIP) exhibit intricate spatial and temporal dynamics in the posterior parietal cortex, presenting decoding challenges such as limited data availability at the biological population level. The practical difficulty in collecting VIP neuronal response data hinders the application of sophisticated decoding models. To address this challenge, we propose a unified spike-based decoding framework leveraging spiking neural networks (SNNs) for both generative and decoding purposes, for their energy efficiency and suitability for neural decoding tasks. We propose the Temporal Spiking Generative Adversarial Networks (T-SGAN), a model based on a spiking transformer, to generate synthetic time-series data reflecting the neuronal response of VIP neurons. T-SGAN incorporates temporal segmentation to reduce the temporal dimension length, while spatial self-attention facilitates the extraction of associated information among VIP neurons. This is followed by recurrent SNNs decoder equipped with an attention mechanism, designed to capture the intricate spatial and temporal dynamics for heading direction decoding. Experimental evaluations conducted on biological datasets from monkeys showcase the effectiveness of the proposed framework. Results indicate that T-SGAN successfully generates realistic synthetic data, leading to a significant improvement of up to 1.75% in decoding accuracy for recurrent SNNs. Furthermore, the SNN-based decoding framework capitalizes on the low power consumption advantages, offering substantial benefits for neuronal response decoding applications., 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 © 2024. Published by Elsevier Ltd.)

Background: Huntington disease (HD) is a genetic neurodegenerative disorder. Given the focus on motor manifestations, nonmotor symptoms are frequently underappreciated in clinical evaluations, despite frequently contributing to primary functional impairment., Recent Findings: A diagnosis of motor-onset as the definition of manifest symptoms misrepresents the complex nature of HD presentation. Despite recent attempt to integrate nonmotor diagnostic criteria, practical guidelines are necessary to inform clinical diagnosis. We propose an HD diagnostic framework and staging system that prioritizes genetic testing, integrates motor and nonmotor symptom considerations in the determination of clinical disease onset and severity, and acknowledges the secondary role of clinically indicated diagnostic assessments, incorporating the broad symptom profiles observed in clinical practice., Implications for Practice: The proposed diagnostic criteria more accurately reflect the presentation of HD and provide greater opportunities for health care professionals to provide appropriate clinical care guidelines for adults with gene-expanded HD., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: The objective of this study was to analyze the temporal trends and demographic/geographical disparities in acute myocardial infarction (AMI)-related mortality among individuals aged 15 and older across the United Sates (US)., Material and Methods: We evaluated death records from 1999 to 2020 that were obtained from the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent changes (APC) were computed, with stratification by year, sex, race/ethnicity, and geographic region., Results: Between 1999 and 2020, 3,016,546 AMI-related deaths were reported in the United States. The overall AAMR was 51.9 per 100,000 (95% CI: 51.8-52.0). Over the course of the study, the crude mortality rate (CMR) increased with age. Males exhibited a consistently higher overall annual AAMR (67.4, 95% CI: 67.3, 67.5) than females (39.5, 95% CI: 39.4, 39.6). In comparison to other races, Black (or African American) people had the highest death rates, with an AAMR of 58.9 (95% CI: 58.7, 59.1). The South region mortality rate (AAMR = 57.7; 95% CI: 57.6, 57.8) was higher than that of the Northeast, Midwest, and West. Specifically, Kentucky had the highest death rate (87.7, 95% CI: 87.0, 88.3), followed by Missouri (80.3, 95% CI: 79.8, 80.8) and Mississippi (85.6, 95% CI: 85.0, 86.6)., Conclusions: During the period from 1999 to 2020, males, Black/African American adults and those living in the South and other nonmetropolitan areas of the country typically had the highest AAMRs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Background: Depression is a common mental disorder, yet it shows low remission rates. The available evidence on personality traits as factors associated with the course of depression has common methodological limitations. Identifying personality traits linked with depression can improve understanding of the course of illness. Therefore, we aimed to investigate personality traits that are associated with the course of depression over 18 months., Methods: longitudinal data of 2366 Adult Psychiatric Morbidity Survey respondents were analysed. Assessments were applied at two-time points (baseline) and follow-up (about 18 months later). We assessed the total score on the screening questionnaire from the Structured Clinical Interview (SCID-II) for the dependent, obsessive-compulsive, and borderline personalities. Depression was measured using the revised Clinical Interview Schedule (CIS-R) version., Results: An increase of one score on the borderline personality scale at baseline increased the odds of experiencing persistent depression by 1.50 times (OR = 1.50, 95 % CI [1.22-1.86]), depression onset by 1.30 times (OR = 1.30, 95 % CI [1.14-1.50]), and recovery by 1.52 times (OR = 1.52, 95 % CI [1.35-1.70]), comparing to no depression group. Elevated scores of dependent personality traits significantly predicted depression persistence (OR = 1.95, 95 % CI [1.52-2.49]). An increase of one score on the obsessive-compulsive personality scale increases the odds of depression onset by 1.21 times (OR = 1.21, 95 % CI [1.04-1.39])., Limitations: The APMS survey defined depression statuses in a limited sense, which may affect the generalisability of these results., Conclusion: The present study confirms previous findings and contributes evidence suggesting that personality dysfunctions worsen depression outcomes., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This article focuses on potential strategies to support primary care researchers in working in partnership with the public and healthcare professionals. Partnership working can potentially to improve the relevance and usefulness of research and ensure better research and health outcomes., Discussion: We describe what we mean by partnership working and the importance of reflecting on power and building trusting relationships. To share power in partnership working, it is essential to critically reflect on the multiple dimensions of power, their manifestations, and your own power. Power can influence relationships and therefore, it is essential to build trust with partners. Next, we outline how the context of primary care research and decisions about who you work with and how to work together, are vital considerations that are imbued with power. Lastly, we suggest different ways of working in partnership to address different dimensions of power. We provide examples from primary care research across Europe regarding how to recognise, tackle, and challenge, invisible, hidden and visible power., Conclusion: We conclude by proposing three calls to actions to encourage researchers working in primary care to consider the multiple dimensions of power and move towards partnership working. First is to use participatory methods to improve the inclusivity of your research. Second is to include patients and the public in decisions about the design, delivery and development of research and its outcomes. Third is to address various systemic and institutional barriers which hinder partnership working.

Corneal diseases represent a growing public health burden, especially in resource-limited settings lacking access to specialized eye care. Artificial intelligence (AI) offers promising solutions for automating the diagnosis and management of corneal conditions. This narrative review examines the application of AI in corneal diseases, focusing on keratoconus, infectious keratitis, pterygium, dry eye disease, Fuchs endothelial corneal dystrophy, and corneal transplantation. AI models integrating diverse imaging modalities (e.g., corneal topography, slit-lamp, and anterior segment OCT images) and clinical data have demonstrated high diagnostic accuracy, often outperforming human experts. Emerging trends include the incorporation of biomechanical data to enhance keratoconus detection, leveraging in vivo confocal microscopy for diagnosing infectious keratitis, and employing multimodal approaches for comprehensive disease analysis. Additionally, AI has shown potential in predicting disease progression, treatment outcomes, and postoperative complications in corneal transplantation. While challenges remain such as population heterogeneity, limited external validation, and the "black box" nature of some models, ongoing advancement in explainable AI, data augmentation, and improved regulatory frameworks can serve to address these limitations., 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 © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflict of Interest: The authors declared that there is no conflict of interest.

Chimeric Antigen Receptor (CAR) T-cells have emerged as a promising immune effector cell-based therapy. With promising results and approval for the treatment of hematological malignancies, we discuss the scope of this novel therapeutic modality in systemic autoimmune diseases and immune-mediated inflammatory disorders refractory to conventional and biological disease-modifying agents.

Background: Cystic fibrosis (CF) is associated with increased resting energy expenditure. However, the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has resulted in a paradigm shift in nutritional status for many people with CF, with increase body mass index and reduction in the need for nutritional support. While these changes are likely to reflect improved clinical status and an associated downregulation of energy expenditure, they may also reflect drug-induced alterations in metabolic perturbations within CF cells. We hypothesise that some of these changes relate to normalisation of mitochondrial respiration in CF., Methods: Using wild-type (WT) and F508del/F508del CFTR human bronchial epithelial cell lines (HBE cell lines) and baby hamster kidney (BHK) cells we examined the impact of ETI on cellular metabolism. We monitored mitochondrial respiration, using Seahorse extracellular flux assays and monitored mitochondrial reactive oxygen species (mROS) and intracellular calcium levels by flow cytometry., Results: Increased mitochondrial respiration was found in HBE cell lines and BHK cells expressing CFTR F508del/F508del when assessing basal, maximal, spare respiratory capacities and ATP production, as well as increased mitochondrial ROS generated via forward electron transport. ETI significantly decreased basal, maximal, spare respiratory capacity and ATP production to WT levels or below. Calcium blocker, BAPTA-AM normalised mitochondrial respiration, suggesting a calcium-mediated mechanism. ETI decreased intracellular calcium levels in CF cells to the same extent as BAPTA-AM, highlighting the importance of calcium and chloride in mitochondrial respiration in CF., Conclusions: CF cell lines exhibit increased mitochondrial respiration, which can be downregulated by ETI therapy through mechanisms involving calcium., Competing Interests: 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., (© 2024 The Authors.)

Background: Sibling sexual abuse is a common form of intra-familial sexual abuse, yet it remains under-studied and under-recognised, leaving many children unprotected and unsupported. Practitioners need rigorously conducted evidence syntheses to inform decision making in this complex practice area., Objective: A scoping review was conducted with the broad research question: What is known about sibling sexual abuse? in order to map the research and to establish areas of knowledge and gaps requiring attention., Method: The review followed the guidelines of Arksey and O'Malley (2005), and through searches of 11 academic databases, 3 grey literature databases, journal handsearch and Google, identified 91 empirical papers for review., Results: While poorly and inconsistently defined, sibling sexual abuse is a common form of child sexual abuse with significant consequences for the whole family. It may involve children of any age and sex, entail the full range of sexual behaviours, and can take place in families from across the socioeconomic spectrum. Disclosure is uncommon during childhood, with multiple barriers including the nature of the caregiving environment in which sibling sexual abuse often takes place. Official records are likely to under-report the frequency and duration of the abuse., Conclusions: There is considerable scope for further research across all aspects of sibling sexual abuse. This paper represents the most comprehensive (albeit not complete) overview of the current body of knowledge in this field to date, and presents key findings as well as a summary of practice and research recommendations., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes, reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in people with enduring illness, but few have explored inflammatory changes. We sought to identify an inflammatory signal and the associated brain function underlying anhedonia among young people with recent-onset psychosis and recent-onset depression., Methods: Resting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from 108 (mean [SD] age = 26.2 [6.2] years; female = 50) participants with recent-onset psychosis (n = 53) and recent-onset depression (n = 55) from the European Union/Seventh Framework Programme-funded PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Time series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and a functional connectivity model were developed to classify participants into an anhedonic group or a normal hedonic group., Results: A repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic recent-onset psychosis/recent-onset depression groups with a balanced accuracy of 63.9% and an area under the curve of 0.61. The functional connectivity model produced a balanced accuracy of 55.2% and an area under the curve of 0.57. Anhedonic group assignment was driven by higher levels of interleukin 6, S100B, and interleukin 1 receptor antagonist and lower levels of interferon gamma, in addition to connectivity within the precuneus and posterior cingulate., Conclusions: We identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: Genomic medicine is revolutionizing health care but requires health care professionals to update their understanding of genomics and its application to clinical practice for successful implementation. To meet this need, Health Education England developed the Master's in Genomic Medicine, a national multiprofessional program to increase genomic literacy in the National Health Service workforce. This study summarizes an evaluation of the program, which will inform its future development., Methods: Underpinned by Moore's evaluation framework, a mixed methods approach was used to characterize (1) learner demographics, (2) perceptions of the program, (3) knowledge and/or qualifications achieved, and (4) the outcome(s) for practice in the workplace., Results: Learners were a diverse cohort of health care professionals, including doctors, health care scientists, nurses and midwives. Participant satisfaction was high for all elements of the program, including the curriculum, learning environment(s), and multiprofessional cohort(s), despite the challenges of engaging working professionals in part-time learning. Both learners and their managers reported enhanced genomic practice after completion of their studies., Conclusion: The Master's in Genomic Medicine program is an effective approach to professional education in genomic medicine. This broad multiprofessional learning complements training aimed at specific groups of health care professionals., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Environmental concerns about microplastics (MPs) have motivated research of their sources, occurrence, and fate in aquatic and soil ecosystems. To mitigate the environmental impact of MPs, biodegradable plastics are designed to naturally decompose, thus reducing the amount of environmental plastic contamination. However, the environmental fate of biodegradable plastics and the products of their incomplete biodegradation, especially micro-biodegradable plastics (MBPs), remains largely unexplored. This comprehensive review aims to assess the risks of unintended consequences associated with the introduction of biodegradable plastics into the environment, namely, whether the incomplete mineralization of biodegradable plastics could enhance the risk of MBPs formation and thus, exacerbate the problem of their environmental dispersion, representing a potentially additional environmental hazard due to their presumed ecotoxicity. Initial evidence points towards the potential for incomplete mineralization of biodegradable plastics under both controlled and uncontrolled conditions. Rapid degradation of PLA in thermophilic industrial composting contrasts with the degradation below 50 % of other biodegradables, suggesting MBPs released into the environment through compost. Moreover, degradation rates of <60 % in anaerobic digestion for polymers other than PLA and PHAs suggest a heightened risk of MBPs in digestate, risking their spread into soil and water. This could increase MBPs and adsorbed pollutants' mobilization. The exact behavior and impacts of additive leachates from faster-degrading plastics remain largely unknown. Thus, assessing the environmental fate and impacts of MBPs-laden by-products like compost or digestate is crucial. Moreover, the ecotoxicological consequences of shifting from conventional plastics to biodegradable ones are highly uncertain, as there is insufficient evidence to claim that MBPs have a milder effect on ecosystem health. Indeed, literature shows that the impact may be worse depending on the exposed species, polymer type, and the ecosystem complexity., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The management of women with premature cervical dilatation and exposed unruptured fetal membranes remains uncertain and controversial. Treatment options may include expectant management or emergency cervical cerclage (ECC). Little is known regarding the effectiveness of individual interventions, or additional therapies. This systematic review aims to summarise all existing evidence to improve understanding of the treatment options and pregnancy outcomes for women presenting with premature cervical dilatation., Methods: Databases were searched using a prospective protocol (CRD42021286275). Studies were eligible for inclusion across five distinct comparison groups if they included women with premature cervical dilatation and reported clinical outcomes. Primary outcome was pregnancy loss (miscarriage, stillbirth, neonatal death and termination of pregnancy). Planned subgroups included singletons and twins, and low-cervical or high-cervical suture. Pairwise random effects meta-analysis calculated in RevMan5.4, single arm random effects proportional meta-analysis calculated using RevMan and R studio. Risk of bias was assessed using Cochrane Risk of Bias tool and Joanna Briggs Institute checklists., Results: 6781 abstracts were screened, and 177 (four randomised controlled trials) studies included in the five analysis groups. Women receiving ECC were significantly less likely to experience pregnancy loss (combined RR 0.48 95 %CI 0.39-0.59 singleton RR 0.48 95 %CI 0.34-0.67 twin only RR 0.39 95 %CI 0.26-0.58) compared to expectant management. Adjuvant amnioreduction with ECC was not found to reduce pregnancy loss (RR 1.12 (95 % CI 0.73-1.72) or any other outcomes compared to ECC without amnioreduction. Women were significantly more likely to experience pregnancy loss (RR3.85 95 %CI 3.13-4.74) after ECC compared to planned cerclage. The probability of intra-operative rupture of membranes at ECC insertion was 3.3 % (95 %CI 1.8-5.1) and the probability of an ECC attempt being abandoned was 2.6 % (95 %CI 1.1-4.6 %)., Discussion: ECC appears to reduce the risk of pregnancy loss for both singletons and twins although the overall quality of evidence is poor. It is important that women are counselled regarding the outcomes following cerclage according to indication. Pregnancy complications are common after ECC although the rates of intra-operative complications are lower than may be anticipated. Randomised trials remain imperative for understanding the role of ECC and adjunctive treatments in preventing pregnancy loss in this condition., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In kidney transplantation, pairing recipients with the highest longevity with low-risk allografts to optimize graft-donor survival is a complex challenge. Current risk prediction models exhibit limited discriminative and calibration capabilities and have not been compared to modern decision-assisting tools. We aimed to develop a highly accurate risk-stratification index using artificial intelligence (AI) techniques. Using data from the UNOS database (156,749 deceased kidney transplants, 2007-2021), we randomly divided transplants into training (80%) and validation (20%) sets. The primary measure was death-censored graft survival. Four machine learning models were assessed for calibration (integrated Brier score [IBS]) and discrimination (time-dependent concordance [CTD] index), compared with existing models. We conducted decision curve analysis and external validation using UK Transplant data. The Deep Cox mixture model showed the best discriminative performance (area under the curve [AUC] = 0.66, 0.67, and 0.68 at 6, 9, and 12 years post-transplant), with CTD at 0.66. Calibration was adequate (IBS = 0.12), while the kidney donor profile index (KDPI) model had lower CTD (0.59) and AUC (0.60). AI-based D-TOP outperformed the KDPI in evaluating transplant pairs based on graft survival, potentially enhancing deceased donor selection. Advanced computing is poised to influence kidney allocation schemes., Competing Interests: Disclosure: T.F. is a current employee of the United States Veterans Health Administration. However, the views and opinions expressed herewith do not reflect the official views or opinions of and are not endorsed by the United States Veteran Health Administration. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Introduction: Abdominal tuberculosis presents in a variety of ways. Different testing modalities must be applied in addition to having a high clinical suspicion to diagnose and initiate therapy. Medications have a good response; however, morbidity has been seen following surgical management of complicated presentations like intestinal obstruction and perforation. There is a paucity of studies in the pediatric age group which evaluate response to the different treatment regimen and identify factors associated with poorer outcomes in children with abdominal tuberculosis., Methods: Patient records of 75 children with abdominal tuberculosis at a single center were evaluated using a questionnaire, covering a 14-year period from 2007 to 2021. Demographic features, presenting signs and symptoms, investigations and treatment details were studied. In- person or telephonic follow-up was conducted to identify treatment outcomes., Results: Incidence of abdominal TB was 7%, of all TB children with a mean age of 10.1 years. Mesenteric lymph nodes were involved in 67% and small intestine in 33% cases. Surgery was required in 22 children. 85% children completed treatment. Small intestine involvement had higher probability of undergoing surgery. Of the 70 children with complete follow up, 64 were well and 6 children succumbed to the disease. Older age, small intestine involvement and surgery were independently associated with higher mortality., Conclusion: Intestinal involvement is associated with greater need for surgical intervention and greater mortality. Adolescents have poorer outcomes. Further studies are required focusing on these individual subgroups to understand the patterns of presentation, causes for mortality and prevention., Level of Evidence: Level 5., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To evaluate healthcare professional (HCP) students clinical learning experiences' whilst undertaking placements in a student-led clinical learning environment (SLCLE) and any changes in self-reported ratings of confidence., Background: The English NHS Long Term Workforce Plan (2023) highlights the need to expand domestic education of HCPs to meet workforce shortages. The demand for quality clinical placements to support the preparation of HCP students remains a challenge globally. A creative solution has been the development of student-led learning clinical environments in healthcare settings. SLCLEs provide high-quality learning experience, increase clinical placement capacity whilst maintaining patient care standards. A multisite NHS Trust adopted this model as evidence suggests HCP students will be better prepared on qualification to adopt registered practitioner professional responsibilities. This model has been integrated across three hospital sites within a large teaching hospital, providing care for a diverse population and designed to accommodate students from a range of HCP disciplines and higher educational institutions., Design: A mixed methods convergent design., Methods: An online survey was administered to SLCLE allocated nursing and allied health profession (AHP) undergraduate and graduate-entry first, second and third-year students (n=132). Face to face focus groups/individual interviews were undertaken with a purposive sample of student participants (n=80) to evaluate their experiences of clinical learning in SLCLEs. Survey data were analysed using descriptive statistics and paired t-tests, interviews using framework method., Results: Undergraduate and graduate-entry students from four UK universities completed the survey (n=132), 103 students (78 %) responded. Most were year 2 students (n=43/42 %), pursuing nursing programmes (n=82/80 %). Most considered the SLCLE met their expectations (n=76/74 %), reported increased confidence post-placement (n=84/82 %), felt supported by staff (n=80/78 %), peers (n=93/90 %) and clinical educators (n=93/90 %). Self-reported confidence scores post-SLCLE were significantly higher than pre-SLCLE. On-line pre-placement information was infrequently accessed yet identified as an omission. Four themes were identified: (i) preconceptions and initial anxiety; (ii) empowerment, growth and a unique learning experience; (iii) collaborative inter-professional learning and support; and (iv) insights and anticipations., Conclusions: The SLCLE allocation enhanced students' confidence and knowledge. Support from clinical educators, ward staff and doctors was perceived as invaluable for creating a positive learning culture. Peer support and opportunities to lead care delivery contributed to students' professional development. The format and method for providing pre-placement information needs review as do strategies for avoiding delays in completing assessment documentation. Overall, the SLCLE experience offers much potential as a nurturing and effective learning environment for HCP students., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)