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Aim: This study examines trends in paracetamol overdoses among Danish adolescents during and following the COVID-19 pandemic., Methods: A retrospective observational study was conducted using data from the national databases, covering all paediatric departments in Denmark from January 2016 to December 2023. Patients between 10 and 19 years of age diagnosed with paracetamol overdose were stratified by sex, age and number of hospital admissions. As the dataset covers the entire population, observed values reflect true parameters. A one-sample t-test compared post-COVID-19 values to the pre-COVID-19 mean., Results: A total of 4.448 patients accounted for 5.794 hospital admissions due to paracetamol overdoses, with a majority being girls. During the second year of the pandemic (2021), a rise in overdose cases (26.5%) and hospital admissions (30.3%) was observed, especially among girls. The average number of admissions per patient increased, indicating repeated self-harm attempts. Cases of severe overdoses leading to acute liver failure increased at Rigshospitalet. These trends reversed post-pandemic., Conclusion: The findings suggest an association between pandemic-related isolation and an increase in adolescent paracetamol overdoses. While rates began to normalise after restrictions were lifted, further research is needed to assess the long-term mental health impact of such restrictions., (© 2025 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and non-genetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Transition to adult care is a challenging and complex process for youth and emerging adults with chronic health and/or mental health conditions. Patient navigation has been proposed to improve care during transition, but previous studies have used single disease cohorts with a nonrandomized design., Objective: To compare the effectiveness of a patient navigator service to reduce emergency department (ED) use among adolescents and emerging adults with chronic health and/or mental health conditions undergoing transition to adult-oriented health care., Design, Setting, and Participants: This was a pragmatic, parallel-group, nonblinded randomized clinical trial design. Patients were followed up for a minimum 12 months and maximum 24 months after enrollment. The setting was the Canadian province of Alberta, with a population of 4.3 million inhabitants, having 3 tertiary care pediatric hospitals serving the entire population with universal health coverage. Participants included youth aged 16 to 21 years, followed up within a diverse array of chronic care clinics, expected to be transferred to adult care within 12 months, residing in Alberta, Canada., Interventions: A 1:1 allocation to either access to a personalized navigator, an experienced social worker within the health services environment, or usual care, for up to 24 months after randomization., Main Outcomes and Measures: All-cause ED visit rate while under observation., Results: A total of 335 participants were randomized over a period of 45 months, 164 (49.0%) to the intervention arm and 171 (51.0%) to usual care. After 1 patient withdrew, 334 participants (usual care: mean [SD] age, 17.8 [0.7] years; 99 female [57.9%]; intervention: mean [SD] age, 17.7 [0.6] years; 81 male [49.7%]) were included in the final data analysis. Among the participants, 131 (39.2%) resided in a rural location, and 126 (37.7%) had a self-reported mental health comorbidity during baseline assessment. We observed significant effect modification in the relationship between intervention and ED visits based on mental health comorbidity. Among those with a self-reported mental health condition, ED visit rates were lower in those with access to the navigator, but the association was not significant (adjusted incidence rate ratio [IRR] 0.75; 95% CI, 0.47-1.19). Among those with no mental health comorbidity, the corresponding adjusted IRR was 1.45 (95% CI, 0.95-2.20)., Conclusions and Relevance: In this randomized clinical trial, the navigator intervention was not associated with a significant reduction in ED visits among youth with chronic health conditions transitioning to adult care. The study did not accrue sufficient sample size to demonstrate a significant difference between groups should it exist., Trial Registration: ClinicalTrials.gov Identifier: NCT03342495.

Importance: Current upper-extremity therapies provide inconsistent outcomes for children with unilateral cerebral palsy. Noninvasive brain stimulation, specifically transcranial direct current stimulation, may enhance motor gains when combined with therapy., Objective: To determine whether the addition of neurostimulation to upper-extremity therapy enhances motor function in children with perinatal stroke and unilateral cerebral palsy., Design, Setting, and Participants: This multicenter, randomized, sham-controlled phase 3 trial was conducted from July 2017 through March 2023. Investigators, treating therapists, outcome assessors, parents, and participants were blinded to intervention allocation. The study took place at 3 tertiary care Canadian pediatric rehabilitation hospitals. From a population-based sample of children 6 to 18 years old with perinatal stroke and disabling unilateral cerebral palsy, 196 children were approached and 107 were excluded., Intervention: Participants were randomly assigned in permuted blocks of 2 (1:1) to receive daily sham or cathodal stimulation to the contralesional motor cortex during 10 days of high-dose, child-centered intensive upper-extremity therapy., Main Outcomes and Measures: The primary end points were changes from baseline to 6 months posttherapy in affected hand function and attainment of child-identified functional goals assessed by the Assisting Hand Assessment and Canadian Occupational Performance Measure. Safety was assessed, including any decrease in the function of either hand. Analysis was intention to treat., Results: Eighty-nine children were enrolled with 45 randomized to sham (62% male, 38% female; mean [SD] age, 10.7 [2.8] years) and 44 to stimulation (52% male, 48% female; mean [SD] age, 10.7 [2.1] years). Eighty-three participants had complete outcome data (42 sham, 41 stimulation). High proportions of children in both groups demonstrated significant functional gains sustained at 6 months (P < .001) with large effect size (Cohen d > 1). There were no differences between groups for mean (SD) change in hand function (5.2 [5.3] vs 4.6 [5.7]; P = .63) or goal attainment (3.0 [2.0] vs 3.6 [2.3]; P = .25). Procedures were safe and well tolerated with no serious adverse events., Conclusions and Relevance: In this study, results showed that patient-centered intensive motor learning programs could produce marked and sustained improvements in upper-extremity function in children with perinatal stroke and unilateral cerebral palsy. The addition of 1 milliampere contralesional motor cortex transcranial direct current stimulation did not improve outcomes compared with sham stimulation., Trial Registration: ClinicalTrials.gov Identifier: NCT03216837.

Abnormalities in thalamocortical crosstalk can lead to neuropsychiatric disorders. Variants in CACNA1G, which encodes the α1G subunit of the thalamus-enriched T-type calcium channel, are associated with absence seizures, intellectual disability, and schizophrenia, but the cellular and circuit consequences of these genetic variants in humans remain unknown. Here, we developed a human assembloid model of the thalamocortical pathway to dissect the contribution of genetic variants in T-type calcium channels. We discovered that the M1531V CACNA1G variant associated with seizures led to changes in T-type currents in thalamic neurons, as well as correlated hyperactivity of thalamic and cortical neurons in assembloids. By contrast, CACNA1G loss, which has been associated with risk of schizophrenia, resulted in abnormal thalamocortical connectivity that was related to both increased spontaneous thalamic activity and aberrant axonal projections. These results illustrate the utility of multi-cellular systems for interrogating human genetic disease risk variants at both cellular and circuit level., Competing Interests: Declaration of interests Stanford University has filed a provisional patent application covering the generation of multi-region assembloids. M.H.P. is on the Board of Directors and holds equity in Graphite Bio. M.H.P. serves on the SAB of Allogene Tx and is an advisor to Versant Ventures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Migration percentage (MP) is the gold standard to assess the severity of hip displacement in children with cerebral palsy, which is measured on anteroposterior hip radiographs. Recently, the ultrasound (US) method has been developed as a safe alternative imaging modality to image and monitor children's hips. However, measuring MP on US images (MP US ) is time-consuming, challenging, and user-dependent. This study aimed to develop machine learning algorithms to automatically measure MP US and validate the algorithms with MP Xray . A combination of signal filtering, convolution neural networks (CNNs), and UNets was applied to segment the regions of interest (ROI), detect edges or feature points, and select the desired US frames. A total of 62 hips including both coronal and transverse scans per hip were acquired, out of which 36 with applying augmentation method were utilized for training, 8 for validation, and 18 for testing. The intraclass correlation coefficient (ICC 2,1 ) and the mean absolute difference (MAD) between the automated MP US versus manual MP Xray were 0.86 and 6.5% ± 5.5%, respectively. To report the MP US , it took an average of 104 s/hip. This preliminary result demonstrated that MP US was able to extract automatically within 2 min with a clinical acceptance accuracy (10%)., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. International Federation for Medical and Biological Engineering.)

Background: To identify early biomarkers that could predict later functional capabilities in preterm children with later cerebral palsy (CP)., Methods: Data from 968 preterm children with later CP were extracted from the Canadian Cerebral Palsy Registry. One hundred eighty-two infants were born before 27 weeks of gestation, 461 infants were born between 27 and 33 weeks, and 325 infants were born between 34 and 37 weeks. Univariate and chi-square analyses were conducted to measure the association between early objective biomarkers and later mobility status defined as Gross Motor Function Classification System (GMFCS) levels IV and V as well as tube feeding dependence., Results: Univariate analysis suggested no significant association between GMFCS levels IV and V or impaired feeding status and bilateral white matter injury on magnetic resonance imaging, high-grade intraventricular hemorrhage on head ultrasound, chorioamnionitis, a birth weight of 1000 to 1500 g or <1000 g, as well as an Apgar score of ≤5 at five minutes of life. Similar results were found for gestational age <28 weeks at birth. Only a significant association between GMFCS levels IV and V and a cord or first hour of life pH of ≤7 was reported (mobility status: odds ratio [OR] 1.95, 95% confidence interval [CI] 1.09 to 3.57) and feeding status: OR 2.23, CI 0.97 to 4.65)]., Conclusions: Prediction of functional outcomes based on specific early biomarkers appears hard to obtain in children with CP born preterm in contrast to those born at term. The complications and causal pathways inherent to prematurity may contribute to making prognostication less determinant., Competing Interests: Declaration of Competing Interest We hereby confirm that all authors have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The transition from pediatric to adult care poses challenges for adolescents and young adults (AYA) with chronic conditions and their caregivers. A patient navigator (PN) intervention may mitigate transition-related barriers., Methods: A qualitative study was conducted within a pragmatic randomized controlled trial. A purposive sample was recruited of AYA with diverse diagnostic and demographic characteristics who worked with the PN and/or their caregivers. Seventeen participants completed semi-structured interviews at baseline and post-intervention and optional journal entries. Thematic analysis was used inductively., Results: Analysis yielded two themes from baseline interviews: 1) uncertainty and hesitation with leaving a place of support, 2) navigator assistance with post-secondary education, and three themes from post-intervention interviews: 1) emotional support, 2) informational and task-focused support, 3) navigator guidance to become more independent., Discussion: Our findings describe the needs of AYA and the experience of PN support; our findings may guide future implementation of PNs in transition care., 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.)

Objectives: To develop evidenced recommendations to allow the global systemic lupus erythematosus (SLE) advocacy community to effectively advocate for change and improve care for patients with SLE., Methods: A Global Working Group consisting of representatives from patient advocacy groups, professional organisations, and the SLE healthcare community defined key areas of unmet need in patients with SLE. Targeted principles for each area of unmet need guided a literature review to investigate the current global situation, pre-existing advocacy efforts, and best practices from other therapy areas. The results from this literature review allowed the Working Group to develop recommendations to improve care for patients with SLE., Results: Barriers faced by patients with SLE can stem from poor recognition of symptoms, which leads to delays in accurate diagnosis, cycling between different healthcare professionals, and inconsistencies in receiving optimal care. Patient access to approved treatments for SLE also remains limited. This Patient Charter, co-developed with a group of internationally recognised clinicians and patient advocates, sets out the minimum standard of care people living with SLE should expect and receive under 4 principles with distinct recommendations for change., Conclusions: The intention is to improve health outcomes by uniting and empowering patients, caregivers, patient groups, and healthcare professionals to advocate for reforms to healthcare practices for people living with SLE.

Objective: Hip migration percentage (MP) measured on anteroposterior pelvis radiographs is the gold standard to assess the severity of hip displacement in children with cerebral palsy (CP). Repeated exposure of these children to ionizing radiation under a hip surveillance program is undesirable. Recently, a semi-automatic approach to measure MP US on ultrasound (US) images was validated in a phantom study. This pilot in vivo study applied the previous phantom method and aimed to determine the reliability and accuracy of the MP US ., Methods: Thirty-four children (23 boys and 11 girls) aged 8.9 ± 3.1 y old and diagnosed with CP were recruited. A total of 59 hips were scanned once, while 43 of these were scanned twice to evaluate the test-retest reliability. Two raters (R1 and R2) manually measured MP US ; procedures included selecting images of interest, cropping a region of interest and removing soft tissues on hip US images. Custom software was developed to measure MP automatically after the manual pre-image processing., Results: The intra-class correlation coefficients (ICC 2,1 ) for the test-retest (R1), intra-rater (R1) and inter-rater (R1 vs R2) reliabilities were 0.90, 0.94 and 0.82, respectively. The standard error of measurement of MP US for all three evaluations was ≤3.0%. The mean absolute difference between MP US and MP X-ray and the percentage of MP US within clinical acceptance error of 10% for R1 and R2 were (R1: 6.2% ± 4.9%, 84.7%) and (R2: 7.6% ± 6.1%, 73.7%), respectively., Conclusion: This study demonstrated that US scans were repeatable and MP US could be measured reliably and accurately., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid exposure., Methods: In a retrospective multicentre cohort study, Cox proportional hazards models examined the relationship between corticosteroid course as a time-varying covariate and time to first relapse. Simon-Makuch and Kaplan-Meier plots identified an optimal dosing strategy., Results: We evaluated 109 patients (62 female, 57%; 41 paediatric, 38%; median age at onset 26 years, (IQR 8-38); median follow-up 6.2 years (IQR 2.6-9.6)). 76/109 (70%) experienced a relapse (median time to first relapse 13.7 months; 95% CI 8.2 to 37.9). In a multivariable model, higher doses of oral prednisone delayed time to first relapse with an effect estimate of 3.7% (95% CI 0.8% to 6.6%; p = 0.014) reduced hazard of relapse for every 1 mg/day dose increment. There was evidence of reduced hazard of relapse for patients dosed ≥12.5 mg/day (HR 0.21, 95% CI 0.07 to 0.6; p = 0.0036), corresponding to a 79% reduction in relapse risk. There was evidence of reduced hazard of relapse for those dosed ≥12.5 mg/day for at least 3 months (HR 0.12, 95% CI 0.03 to 0.44; p = 0.0012), corresponding to an 88% reduction in relapse risk compared with those never treated in this range. No patient with this recommended dosing at onset experienced a Common Terminology Criteria for Adverse Events grade >3 adverse effect., Conclusions: The optimal dose of 12.5 mg of prednisone daily in adults (0.16 mg/kg/day for children) for a minimum of 3 months at the onset of MOGAD delays time to first relapse., Competing Interests: Competing interests: BPT receives a University of Sydney postgraduate scholarship and a stipend from CIA Ramanathan’s Royal Australasian College of Physicians Research Establishment Fellowship. RCD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the NHMRC (Australia; Investigator Grant). He has also received honoraria from Biogen Idec as an invited speaker, and is on the IDMC for a Roche RCT in paediatric MS. He is on the medical advisory board (non-remunerated position). TAH has received research funding from MS Australia, the NHMRC Medical Research Future Fund (Australia), the Brain Foundation and has received honoraria for talks, advisory boards or support for scientific meetings from Bayer-Schering, Novartis, Biogen Idec, Merck, Teva, Alexion, Bristol Myers Squibb and Sanofi-Genzyme. AVDW receives funding from MS Australia, the NHMRC and the Trish Foundation. She has received research support from Roche pharmaceuticals, Biogen, Novartis and Merck. She has received honoraria for talks, advisory boards, and travel support from Novartis and Merck. She serves as the COO of the MSBase Foundation. JLS received travel compensation from Biogen, Merck, Novartis; has been involved in clinical trials with Biogen, Novartis, Roche; her institution has received honoraria for talks and advisory board service from Biogen, Merck, Novartis, Roche. She is on the board of directors for MSPlus. HB has received institutional compensation (To Monash University) for advisory board or trial steering committee membership or speaker bureaus from Biogen, Merck, Novartis, Roche, and UCB Pharma. Institutional Research Support to Monash University or MSBase Foundation from Merck, Biogen, Roche, Novartis, UCB Pharma, Alexion, Teva, NMHRC (Australia), MRFF (Australia), MS Australia, TRISH MS Research Foundation, Pennycook Foundation and Monash University. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis, and Sanofi-Genzyme, has received speaker’s honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme, and was the recipient of an unencumbered research grant from Biogen-Idec. MB received research grants from Genzyme-Sanofi, Novartis, Biogen, Merck and BMS; and is a Research Consultant for RxMx and Research Director for the Sydney Neuroimaging Analysis Centre. He is on the board of the Research Management Council of MS Australia, or the Trish Foundation Board. SWR has received travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical / biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. He is cofounder/shareholder of RxPx health, National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc subcommittee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid), Medical advisor (unpaid) to various patient and advocacy groups. Funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. FB has received research funding from NSW Health, MS Australia, the NHMRC (Australia), the Medical Research Future Fund (Australia), The MOG Project (Apollo Grant) and Novartis. She was on an advisory board for Novartis and Merck, and has been an invited speaker for Biogen, Novartis and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. TK served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation, the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology and has been an invited speaker for educational/research sessions coordinated by Biogen, Alexion, Novartis, Excemed and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. All other authors have no relevant disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To optimise the organisation of care and encourage the adoption of good clinical practices, the RarERN Path © methodology was designed within ERN ReCONNET. The aim of our work was to report the application of RarERN Path © on systemic sclerosis within the ERN ReCONNET centres, providing a feasible and flexible organisational reference model for optimising the systemic sclerosis care pathway in different countries., Methods: RarERN Path © is a six-phase methodology which enables the creation of a reference organisational model co-designed on the basis of the expertise of different stakeholders. It foresees six phases, ranging from the map of existing patients' care pathways and patients' stories, to the consensus on a common organisational patient care pathways, and its key performance indicators definition., Results: The agreed reference model highlights the importance of having an organisational flow for referrals that foresees how patients may access directly the specialised unit from the different referrals. Specific specialised visits were considered as mandatory to be organised and they included cardiologist, pneumologist, gastroenterologist, psychologist, nephrologist, dermatologist, wound care specialist/nurses and other healthcare professionals (such as nurses, social workers and nutritional counselling). Moreover, specific services related to therapy were highlighted as strongly recommended to be organised, mainly represented by infusion therapy and wound care, as well as occupation therapy and physiotherapy., Conclusion: The organisational model emerged from our investigation emphasises that the organisation of specific services for systemic sclerosis treatment should be organised as a solid support for implementing the existing recommendations on systemic sclerosis management in real life., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Brain-computer interfaces (BCI) offer promise to the play of children with significant physical impairments, as BCI technology can enable disabled children to control computer devices, toys, and robots using only their brain signals. However, there is little research on the unique needs of disabled children when it comes to BCI-enabled play. Thus, this paper explored the lived experiences of play for children with significant physical impairments and examined how BCI could potentially be implemented into disabled children's play experiences by applying a social model of childhood disability. Descriptive qualitative methodology was employed by conducting four semi-structured interviews with two children with significant physical impairments and their parents. We found that disabled children's play can be interpreted as passive or active depending on one's definition and perceptions surrounding play. Moreover, disabled children continue to face physical, economic, and technological barriers in their play, as well as play restrictions from physical impairments. We urge that future research should strive to directly hear from disabled children themselves, as their perspectives may differ from their parents' views. Also, future BCI development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.Implications for RehabilitationAssistive technology research should strive to examine the social, infrastructural, and environmental barriers that continue to disable and restrict participation for disabled children and their families through applying a social model of childhood disability and other holistic frameworks that look beyond individual factorsFuture research that examines the needs and lives of disabled children should strive to directly seek the opinions and perspectives of disabled children themselvesBrain-computer interface development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.

In arthropods, hematophagy has arisen several times throughout evolution. This specialized feeding behavior offered a highly nutritious diet obtained during blood feeds. On the other hand, blood-sucking arthropods must overcome problems brought on by blood intake and digestion. Host blood complement acts on the bite site and is still active after ingestion, so complement activation is a potential threat to the host's skin feeding environment and to the arthropod gut enterocytes. During evolution, blood-sucking arthropods have selected, either in their saliva or gut, anticomplement molecules that inactivate host blood complement. This review presents an overview of the complement system and discusses the arthropod's salivary and gut anticomplement molecules studied to date, exploring their mechanism of action and other aspects related to the arthropod-host-pathogen interface. The possible therapeutic applications of arthropod's anticomplement molecules are also discussed., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Background: Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased healthspan. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand, and meet the healthcare, workforce, wellbeing, and socioeconomic needs of ageing populations, while supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies., Methods: The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19 th , 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥70% for approval., Results: The accepted criteria for an ageing-related pathology, disease or syndrome were: Develops and/or progresses with increasing chronological age.Should be associated with, or contribute to, functional decline, or an increased susceptibility to functional decline.Evidenced by studies in humans., Conclusions: Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.

Background: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study., Methods: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOne ® CDx. To further hypothesis-driven correlative analyses, agnostic heat-map visualizations of the FoundationOne ® CDx tumor dataset were used to assess overall mutational landscape and identify additional candidate predictive biomarkers of response., Results: All patients enrolled (N = 61) had TNBC. In the biomarker analysis population, 75.0% (39/52) and 25.0% (13/52) of patients exhibited BRCA1 and BRCA2 mutations, respectively. Strong concordance (97.8%) was observed between tumor BRCA and germline BRCA mutations, and 90.5% (38/42) of patients with tumor BRCA mutations evaluable for somatic-germline-zygosity were predicted to exhibit BRCA loss of heterozygosity (LOH). No patients had non-BRCA germline DNA damage response (DDR) gene variants with known/likely pathogenicity, based on a panel of 14 non-BRCA DDR genes. Ninety-eight percent of patients had TP53 mutations. Genomic LOH, assessed continuously or categorically, was not associated with response., Conclusion: The results from this exploratory biomarker analysis support the central role of BRCA and TP53 mutations in tumor pathobiology. Furthermore, these data support assessing germline BRCA mutational status for molecular eligibility for talazoparib in patients with TNBC., (© 2024. The Author(s).)

Tracking the position and orientation of a two-dimensional (2D) ultrasound scanner to reconstruct a 3D volume is common, and its accuracy is important. In this study, a specific miniaturized electromagnetic (EM) tracking system was selected and integrated with a 2D ultrasound scanner, which was aimed to capture hip displacement in children with cerebral palsy. The objective of this study was to determine the optimum configuration, including the distance between the EM source and sensor, to provide maximum accuracy. The scanning volume was aimed to be 320 mm × 320 mm × 76 mm. The accuracy of the EM tracking was evaluated by comparing its tracking with those from a motion capture camera system. A static experiment showed that a warm-up time of 20 min was needed. The EM system provided the highest precision of 0.07 mm and 0.01° when the distance between the EM source and sensor was 0.65 m. Within the testing volume, the maximum position and rotational errors were 2.31 mm and 1.48°, respectively. The maximum error of measuring hip displacement on the 3D hip phantom study was 4 %. Based on the test results, the tested EM system was suitable for 3D ultrasound imaging of pediatric hips to assess hip displacement when optimal configuration was used., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Cannabis use among individuals with cancer is best understood using survey self-report. As cannabis remains federally illegal, surveys could be subject to nonresponse and measurement issues impacting data quality. We surveyed individuals using medical cannabis for a cancer-related condition in the Minnesota Medical Cannabis Program (MCP). Although survey responders are older, there are no differences by race and ethnicity, gender, or receipt of reduced cannabis registry enrollment fee. Responders made a more recent purchase and more recently completed an independent symptom assessment for the registry than nonresponders, suggesting some opportunity for nonresponse error. Among responders, self-report and MCP administrative data with respect to age, race, gender, registry certification, and cannabis purchase history were similar. Responders were less likely to report receipt of Medicaid than would be expected based on registry low-income enrollment eligibility. Although attention should be paid to potential for nonresponse error, surveys are a reliable tool to ascertain cannabis behavior patterns in this population., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Maternal autoimmune rheumatic diseases can influence the outcomes of children through several life stages. During pregnancy, maternal inflammation and autoantibodies can hinder fetal development and lead to growth restriction, preterm birth, and low birth weight; prematurity, especially at extreme gestational ages, can in turn impair future child health. Treatment with compatible immunomodulatory drugs and preventive medications aims to keep maternal disease under control and minimise the risk of adverse pregnancy outcomes. However, concerns have been raised about the effects of immunomodulatory drugs on neonatal conditions (ie, the risk of serious infections, inadequate responses to vaccinations, and organ toxicity) and long-term outcomes (metabolic and cardiovascular problems and neurodevelopmental disorders). Among the unmet needs of parents with autoimmune rheumatic diseases, there is the estimation of risk for the children to develop autoimmune disorders and the need for reassurance about parenting capacity while living with a chronic condition. This Series paper provides a comprehensive overview of the literature and guidance on discussing these topics with patients., Competing Interests: Declaration of interests LA reports consulting fees from UCB and speaking and writing fees from AlfaSigma, GSK, Janssen, Novartis, Pfizer, UCB, and the Werfen Group. JA is the Chair of Lupus Europe, which is funded mostly by grants or donations from pharmaceutical companies (Amgen/Horizon, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Galapagos, GSK, Idorsia, Janssen, Merck, Novartis, Otsuka, Roche, and UCB), none of which exceeds 25% of the total funds collected and none of whom have a say on the content of studies or work produced by Lupus Europe. TA reports consulting fees from Novartis and speaking and writing fees from AbbVie, Novartis, Pfizer, and Swedish Orphan Biovitrum. CDC reports research grants from Amgen, AstraZeneca, Genzyme Sanofi-Aventis, Gilead, GSK, Hoffman La-Roche-Genentech, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma Global FZE, Takeda, the Gerber Foundation, and UCB. NM reports consulting fees as an expert advisor from RSM Consulting; speaking fees from Chiesi; and serves as a data safety monitoring board member in two National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) trials and as the Trial Steering Committee Chair in a NIHR HTA trial. AT reports consulting fees from GSK and UCB and participated in advisory boards for Galapagos and UCB. All other authors declare no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau ( MAPT ) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.

Curvatures of the body can disrupt fluid flow and affect hydrodynamic resistance. The purpose of this study was to evaluate the effect of a feedback intervention on glide performance and torso morphology. Eleven male and female national swimmers performed glides before and after augmented feedback. Feedback consisted of self-modelling visual feedback and verbal cuing, to manipulate body curvatures that affect hydrodynamic resistance. Two-dimensional landmark position data (knee, hip and shoulder) were used to enable computation of glide factor and glide coefficient as indicators of glide efficiency; posture (trunk incline and hip angle); and performance (horizontal velocity). Underwater images of the swimmers were manually traced to derive transverse and sagittal diameters, cross-sectional areas, and continuous form outlines (anterior and posterior) of the torso. Maximum rate of change in cross-sectional area and form gradient progressing caudally, were calculated for torso segments: shoulder-chest, chest-waist, waist-hip. Mean velocity, glide factor and glide coefficient values significantly ( p < 0.001) improved due to the intervention, with large effect size ( d ) changes 0.880 ( p = 0.015), 2.297 and 1.605, respectively. Significant changes to form gradients were related to reductions in lumbar lordosis and chest convexity. The study provides practical cuing phrases for coaches and swimmers to improve glide efficiency and performance.

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Stramenopile algae contribute significantly to global primary productivity, and one class, Eustigmatophyceae, is increasingly studied for applications in high-value lipid production. Yet much about their basic biology remains unknown, including the nature of an enigmatic, pigmented globule found in vegetative cells. Here, we present an in-depth examination of this "red body," focusing on Nannochloropsis oceanica. During the cell cycle, the red body forms adjacent to the plastid, but unexpectedly it is secreted and released with the autosporangial wall following cell division. Shed red bodies contain antioxidant ketocarotenoids, and overexpression of a beta-carotene ketolase results in enlarged red bodies. Infrared spectroscopy indicates long-chain, aliphatic lipids in shed red bodies and cell walls, and UHPLC-HRMS detects a C32 alkyl diol, a potential precursor of algaenan, a recalcitrant cell wall polymer. We propose that the red body transports algaenan precursors from plastid to apoplast to be incorporated into daughter cell walls., (© 2024. The Author(s).)

Background: Intensive manual therapy is important for improving lifelong upper limb motor outcomes for infants and toddlers with cerebral palsy. This play-based therapy is delivered by caregivers who are coached by occupational therapists. However, access to this therapy is very limited for Canadian children with cerebral palsy younger than two years old. This project aims to first identify barriers and facilitators and then design implementation strategies to support early intensive manual therapy delivery for infants and toddlers with cerebral palsy across Canada., Methods: A mixed-methods sequential explanatory design will be used with four consecutive phases. The updated Consolidated Framework for Implementation Research will guide the study. Quantitative data will be collected from a survey in Phase One. Participants will be recruited from three groups: (1) Caregivers of children with cerebral palsy six years old and younger who are eligible for manual therapy; (2) occupational therapists who treat children with cerebral palsy; and (3) healthcare administrators or people responsible for managing pediatric occupational therapy programs. In Phase Two, quantitative data from the survey will be used to map to implementation strategies known to be effective at addressing the identified modifiable barriers and facilitators. Phase Three will collect qualitative data from semi-structured interviews for the purpose of explaining Phase One quantitative findings in greater depth, and for understanding the appropriateness of strategies identified in Phase Two. The participant recruitment strategy and interview guide content for Phase Three will be informed by results of Phase One. Phase Four will use a modified nominal group technique to refine and prioritize an implementation strategy toolbox. Results will be widely disseminated to knowledge users to provide them with tailorable strategies to increase delivery of early intensive manual interventions., Discussion: This study will provide a comprehensive understanding of the barriers and facilitators to implementation of early intensive manual therapy for young children with cerebral palsy in Canada. A toolbox of evidence-based and tailorable implementation strategies will be disseminated nationally to support uptake of early intensive manual therapy into clinical practice for young children with cerebral palsy., (© 2024. The Author(s).)

Background : This study investigated how different hearing profiles influenced melodic contour identification (MCI) in a real-world concert setting with a live band including drums, bass, and a lead instrument. We aimed to determine the impact of various auditory assistive technologies on music perception in an ecologically valid environment. Methods : The study involved 43 participants with varying hearing capabilities: normal hearing, bilateral hearing aids, bimodal hearing, single-sided cochlear implants, and bilateral cochlear implants. Participants were exposed to melodies played on a piano or accordion, with and without an electric bass as a masker, accompanied by a basic drum rhythm. Bayesian logistic mixed-effects models were utilized to analyze the data. Results : The introduction of an electric bass as a masker did not significantly affect MCI performance for any hearing group when melodies were played on the piano, contrary to its effect on accordion melodies and previous studies. Greater challenges were observed with accordion melodies, especially when accompanied by an electric bass. Conclusions : MCI performance among hearing aid users was comparable to other hearing-impaired profiles, challenging the hypothesis that they would outperform cochlear implant users. A cohort of short melodies inspired by Western music styles was developed for future contour identification tasks.

Background: Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients., Methods: MOG-IgG-seropositive confirmed adult MOGAD patients were included (n=202). Serum MOG-IgG and epitope binding were determined by validated flow cytometry live cell-based assays. Associations between epitopes, disease course, clinical phenotype, Expanded Disability Status Scale and Visual Functional System Score at onset and last review were evaluated., Results: Of 202 MOGAD patients, 150 (74%) patients had MOG-IgG that recognised the immunodominant proline42 (P42) epitope and 115 (57%) recognised histidine103/serine104 (H103/S104). Fifty-two (26%) patients had non-P42 MOG-IgG and showed an increased risk of a relapsing course (HR 1.7; 95% CI 1.15 to 2.60, p=0.009). Relapse-freedom was shorter in patients with non-P42 MOG-IgG (p=0.0079). Non-P42 MOG-IgG epitope status remained unchanged from onset throughout the disease course and was a strong predictor of a relapsing course in patients with unilateral optic neuritis (HR 2.7, 95% CI 1.06 to 6.98, p=0.038), with high specificity (95%, 95% CI 77% to 100%) and positive predictive value (85%, 95% CI 45% to 98%)., Conclusions: Non-P42 MOG-IgG predicts a relapsing course in a significant subgroup of MOGAD patients. Patients with unilateral optic neuritis, the most frequent MOGAD phenotype, can reliably be tested at onset, regardless of age and sex. Early detection and specialised management in these patients could minimise disability and improve long-term outcomes., Competing Interests: Competing interests: MF-P has received research grant from MS Australia and travel compensation from Merck. MB reports research grants from Genzyme-Sanofi, Novartis, Biogen, Merck and BMS; and is a Research Consultant for RxMx and Research Director for the Sydney Neuroimaging Analysis Centre. SWR has received funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects of which he is a member has been received from bodies and charities: NHMRC, NBA, MAA, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sanofi. MM has served on scientific and commercial advisory boards for Merck Serono. AvdW has received travel support from Merck Serono, Novartis, Biogen, Roche and Sanofi. She has served on scientific and commercial advisory boards for Merck, Novartis, Sanofi and Roche, and has received unencumbered research grants from Novartis, Biogen, Merck and Roche. JLS has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Bayer Health Care, Biogen, Genzyme Sanofi, Merck, Novartis and TEVA. AGK has in recent times received speaker honoraria and Scientific Advisory Board fees from Bayer, BioCSL, Biogen-Idec, Lgpharma, Merck, Novartis, Roche, Sanofi-Aventis, Sanofi-Genzyme, Teva, NeuroScientific Biopharmaceuticals, Innate Immunotherapeutics, and Mitsubishi Tanabe Pharma. His work has received grant funding from the Eyewall Foundation, Trish MS Foundation, MS Australia, MS Western Australia, the MS Base Foundation, the National Health and Medical Research Council of Australia, and the National Multiple Sclerosis Society, USA. He is an investigator in clinical trials sponsored by Biogen Idec and Novartis. TK served on scientific advisory boards for BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis and Sanofi-Genzyme, has received speakers honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme, and was the recipient of an unencumbered research grant from Biogen-Idec. RCD received research funding from the Petre Foundation and National Health and Medical Research Council (Australia). He has received honoraria form Biogen Idec and Merck Serono as invited speaker. SR received research funding from the National Health and Medical Research Council (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She serves as a consultant on an advisory board for UCB and Limbic Neurology, The MOG Project and the Sumaira Foundation, and has been an invited speaker for Biogen, Excemed, Alexxion, Limbic Neurology, and Novartis. FB has received research funding from NSW Health, MS Australia, the National Health Medical Research Council (Australia), the Medical Research Future Fund (Australia) and investigator-initiated research grant from Novartis. She was on an advisory boards for Novartis, Merck and The MOG Project and the Sumaira Foundation, and has been an invited speaker for Biogen, Novartis and Limbic Neurology., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Towards the end of the 19th century and the early 20th century, France was the world's largest producer of antimony, especially due to the rich deposits in the Brioude-Massiac area. Even though all the mining and smelting activities are long gone, there are still some remains of those activities. The most original of those is the use of roasting slags as aggregates in former plant walls or industrial building. They are macroscopically characterised by a black or red colour with a vesicular aspect similar to natural pozzolanas. Common petrography and mineralogy tools have been used to characterise those slags: optical mineralogy, scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction (XRD). To gain an insight into their mineral complexity, a QEMSCAN map has been produced. The mineralogy is typical of high-temperature slags: cristobalite, quartz, mullite, fayalite-forsterite series and spinel. The antimony content is quite high, up to seven percent, under the form of various antimony oxides and native antimony., (© 2023 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)

Introduction: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health., Methods: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes., Results: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value., Conclusions: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health., Funding: None., Trial Registration: Not relevant., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

The optimal utilization of biomass relies heavily on the specific material and individual needs. Cereal biomass by-products can potentially be employed in thermochemical processes such as pyrolysis and gasification. To compare biomass sources, ultimate analysis, biochar potential, proximate analysis, thermal gravimetric analysis, price per megajoule generated heat, surface texture, and availability are used. A global survey of biomass wastes and opportunities for heat generation is presented in the current article. Here, nine different cereal-based agricultural waste products (barley, wheat, millet, oats, rice, rye straw, sorghum straw/stalk, and maize cob) are studied. Cereal wastes are compared based on calorific value, water content, volatile matter, ash content and ash chemical composition, bulk density, charring properties, availability, and transportation. According to the estimate, 156 million metric tonnes per year, or 6% of India's total emissions, could be eliminated by rice husk alone. Wheat straws, on the other hand, can cut emissions by 2%. Additionally, processing these nine feedstocks might result in the production of 40 GW of electrical energy, which would increase the installed capacity of India's national electric grid by 9%., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Perinatal stroke describes a group of focal, vascular brain injuries that occur early in development, often resulting in lifelong disability. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI). Though perinatal stroke is typically considered a motor disorder, other comorbidities commonly exist including attention-deficit hyperactivity disorder (ADHD) and deficits in executive function. Rates of ADHD symptoms are higher in children with perinatal stroke and deficits in executive function may also occur but underlying mechanisms are not known. We measured resting state functional connectivity in children with perinatal stroke using previously established dorsal attention, frontoparietal, and default mode network seeds. Associations with parental ratings of executive function and ADHD symptoms were examined. A total of 120 participants aged 6-19 years [AIS N = 31; PVI N = 30; Controls N = 59] were recruited. In comparison to typically developing peers, both the AIS and PVI groups showed lower intra- and inter-hemispheric functional connectivity values in the networks investigated. Group differences in between-network connectivity were also demonstrated, showing weaker anticorrelations between task-positive (frontoparietal and dorsal attention) and task-negative (default mode) networks in stroke groups compared to controls. Both within-network and between-network functional connectivity values were highly associated with parental reports of executive function and ADHD symptoms. These results suggest that differences in functional connectivity exist both within and between networks after perinatal stroke, the degree of which is associated with ADHD symptoms and executive function., (© 2023. The Author(s).)

Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global photosynthetic productivity, the pathway for its biosynthesis has remained elusive. Here we define the CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of a dinoflagellate mutant deficient in chlorophyll c. CHLCSs are proteins with chlorophyll a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found in peridinin-containing dinoflagellates; other chlorophyll c-containing algae utilize enzymes with only the 2OGD domain or an unknown synthase to produce chlorophyll c. 2OGD-containing synthases across dinoflagellate, diatom, cryptophyte, and haptophyte lineages form a monophyletic group, 8 members of which were also shown to produce chlorophyll c. Chlorophyll c 1 to c 2 ratios in marine algae are dictated in part by chlorophyll c synthases. CHLCS heterologously expressed in planta results in the accumulation of chlorophyll c 1 and c 2 , demonstrating a path to augment plant pigment composition with algal counterparts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence., Methods: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item., Results: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease., Conclusion: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion., Competing Interests: Competing interests: AF reports honoraria and/or consulting fees from Lilly, Boehringer, Novartis, Abbvie, Astra Zeneca, GSK, MSD, Pfizer, UCB, Amgen, Aenorasis, support for attending meetings from UCB. MK reports honoraria and/or consulting fees from GSK, participation in advisory boards from GSK, Astra Zeneca, Amgen. JA reports honoraria and/or consulting fees from Novartis, Astra Zeneca, support for attending meetings from Novartis, Astra-Zeneca, participation in advisory boards from Roche, Astra-Zeneca (all paid to Lupus Europe). MA reports honoraria and/or consulting fees from AbbVie, Astra Zeneca, GSK, Otsuka, Roche, support for attending meetings from Pfizer. LA reports grants from GSK, honoraria and/or consulting fees from Alexion, Alpine, Amgen, Astra Zeneca, AbbVie, Biogen, BMS, Boehringer-Ingelheim, Chugai, GSK, Grifols, Idorsia, Janssen, Kezar, Lilly, Medac, Novartis, Ono pharmaceuticals, Pfizer, Roche, UCB, support for attending meetings from Novartis, Astra-Zeneca. INB reports grants from GSK, Janssen, honoraria and/or consulting fees from Astra Zeneca, GSK, Eli Lilly, UCB, MSD, participation in advisory boards from Aurinia, Astra Zeneca, ILTOO. RC reports honoraria, consulting fees and/or participation in advisory boards from AstraZeneca, Celgene, GSK, Janssen, Lilly, Pfizer, UCB, Rubió, Werfen. AD reports honoraria and consulting fees from Otsuka, Astra Zeneca, GSK, Lilly. TD reports consulting fees from Roche, Novartis, GSK, Astra Zeneca, participation in advisory boards from GNE, Roche, Novartis. DDG reports grants from Abbvie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, UCB, consulting fees from Abbvie, Amgen, Astra Zeneca, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB. FAH reports grants from GSK, Roche. DJ reports grants from GSK, Roche, CSL Vifor, honoraria and consulting fees from Astra Zeneca, Chemocentryx, GSK, Novartis, Takeda, CSL Vifor, participation in advisory boards from Chinook, GSK, stocks in Aurinia. LK reports honoraria fees from Janssen, Takeda, support for attending meetings from Abbvie, Astra Zeneca, CSL Behring, participation in advisory boards from Swixx Pharma, Roche, Astra Zeneca. CCM reports honoraria fees from GSK, support for attending meetings from Novartis. EFM reports grants from AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Genentech, GlaxoSmithKline, Janssen, and UCB, honoraria and/or consulting fees from AbbVie, Astra Zeneca, Biogen, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Galapagos, Genentech, Gilead, GlaxoSmithKline, IGM, Janssen, Novartis, Servier, Wolf, Zenas, support for attending meetings from Astra Zeneca, Roche. GM reports honoraria fees from GSK, Roche, Otsuka, participation in advisory boards from GSK, Otsuka. MM reports honoraria and/or consulting fees from Astra Zeneca, Eli Lilly, GSK, UCB, Janssen, participation in advisory boards from Idorsia. JM reports grants from GSK, honoraria and/or consulting fees from GSK, Astra Zeneca, Otsuka, BMS, participation in advisory boards from GSK, Astra Zeneca, BMS. GN reports honoraria and/or consulting fees from Sobi, GSK, Miltenyi Biotech, Swixx Biopharma, AbbVie, Lilly, Richter, Amgen, Roche, Kedrion, support for attending meetings from Roche, AbbVie, Sobi, Biotest. SVN reports honoraria and/or consulting fees from Astra Zeneca, Boehringer Ingelheim, Idorsia, Astellas, Novartis, GSK, Roche, support for attending meetings from Pfizer, participation in advisory boards from Biogen. IP reports grants from Aurinia, BMS, GSK, Otsuka, Roche, honoraria and/or consulting fees from Astra Zeneca, GSK, Janssen, Novartis, Otsuka, Roche, participation in advisory boards from Astra Zeneca, GSK, Novartis, Otsuka, medical writing from Astra Zeneca, GSK. JMPR reports grants from GSK, Pfizer, honoraria fees from GSK, Astra Zeneca, Lilly, support for attending meetings from GSK, Astra Zeneca, participation in advisory boards from GSK, Otsuka, Gebro, Astra Zeneca, Boehringer-Ingelheim, MSD. BAPE reports grants from Janssen, support for attending meetings from Astra Zeneca, participation in advisory boards from Astra Zeneca, GSK. MS reports grants from GSK, Astra Zeneca, honoraria and/or consulting fees from Astra Zeneca, GSK, Otsuka, UCB, participation in advisory boards from GSK. JSS reports grants from AbbVie, Astra Zeneca, Lilly, Galapagos, royalties or licenses from Elsevier, honoraria and/or consulting fees from AbbVie, Galapagos/Gilead, Novartis, BMS, Samsung, Sanofi, Chugai, R-Pharma, Lilly, MSD, Janssen, participation in advisory boards from Astra Zeneca. ES reports stocks in Astra Zeneca. YKOT reports grants from Mitsubishi-Tanabe, Eisai, Chugai, Taisho, consulting fees from Lilly, Astra Zeneca, AbbVie, Gilead, Chugai, Boehringer-Ingelheim, GSK, Eisai, Taisho, BMS, Pfizer, Taiho. MGT reports grants from Genesis, GSK, MSD, UCB, consulting fees from GSK, Lilly and UCB. CW reports grants from Versus Arthritis, British Society for Rheumatology, Lupus UK, honoraria fees from UCB, support for attending meetings from AbbVie. AT reports honoraria fees from UCB, GSK, participation in advisory boards from UCB, Galapagos. GB reports grants from GSK, Astra Zeneca, Pfizer, honoraria and/or consulting fees from Lilly, Aenorasis, Novartis, AstraZeneca, GSK, SOBI, Pfizer, participation in advisory boards from Novartis. DTB reports unrestricted investigational grants from GSK, honoraria and/or consulting fees from GSK, Astra-Zeneca, Pfizer. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This chapter explores the intricate interactions between neurons and astrocytes within the nervous system with a particular emphasis on studies conducted in human tissue or with human cells. We specifically explore how neuron-astrocyte interactions relate to processes of cellular development, morphology, migration, synapse formation, and metabolism. These findings enrich our understanding of basic neurobiology and how disruptions in these processes are relevant to human diseases.The study of human neuron-astrocyte interactions is made possible because of transformative in vitro advancements that have facilitated the generation and sustained culture of human neural cells. In addition, the rise of techniques like sequencing at single-cell resolution has enabled the exploration of numerous human cell atlases and their comparisons to other animal model systems. Thus, the innovations outlined in this chapter illuminate the convergence and divergence of neuron-astrocyte interactions across species. As technologies progress, continually more sophisticated in vitro systems will increasingly reflect in vivo environments and deepen our command of neuron-glial interactions in human biology., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021., Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA 2 DS 2 -VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced., Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care., Competing Interests: L.F reports being supported by a research grant from the Health Research Foundation of Central Denmark Region. Consultant for BMS/Pfizer and AstraZeneca. A.B reports lecture fees from Boehringer-Ingelheim and Bristol-Myers Squibb; research grants from Theravance, The Zealand Region, the Canadian Institutes of Health Research, and the Danish Heart Foundation, grants from Independent Research Fund Denmark outside this work. DD reports lecture fees from BMS and Pfizer. SPJ reports grants from EU, institutional research grant from BMS/Pfizer. Consultant work for BMS/Pfizer. NV reports being supported by a research grant from the Danish Cardiovascular Academy (PD2Y-2022002-DCA). Consultant for AstraZenaca. No fees were received personally. The authors report no other conflicts of interest in this work., (© 2023 Frost et al.)

Purpose: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer., Patients and Methods: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival., Results: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated., Conclusion: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

The torso muscles play important roles in longitudinal rotation between the upper and lower torso on land but demands on these muscles at different swimming speeds and their role in torso twist in front crawl remains unclear. We aimed to compare torso muscle activity at different front crawl speeds and to assess the relationships between torso muscle activity and torso twist. Three-dimensional kinematics and torso muscle EMG data were collected from 15 male swimmers during middle-distance and sprint front crawl. Internal oblique, external oblique, and rectus abdominis, but not erector spinae, activities were greater at sprint than middle-distance pace. Sprint swimmers are likely to benefit from focusing training on the abdominal muscles. Cross-correlation peak coefficients between muscle activity and torso twist occurred with 517-775 and 400-600 ms lag at middle-distance and sprint paces (respectively). These lags are beyond the torso muscle electromechanical delay (~220 ms) and are too long for these muscles to produce movement changes. Further, peak coefficients coincided with both positive and negative shifts, indicating that muscle activity did not always precede kinematic changes. The torso muscles are therefore likely to play a greater role in maintaining stability and controlling posture in front crawl than producing torso twist.

Systemic Lupus Erythematosus (SLE) imposes a great burden on the lives of patients. Patients' and physicians' concerns about the disease diverge considerably. Physicians focus on controlling disease activity to prevent damage accrual, while patients focus on symptoms that impact on Health-Related Quality of Life (HRQoL). We explored the physicians' and patients' perspective and the potential role of Patient Reported Outcomes (PROs). Physicians are aware of the theoretical usefulness of PROs to collect information deriving from the patients' perspective. However, they often do not know how to interpret and use these questionnaires in a real shared therapeutic strategy. For the patients, it's important to be seen as a whole person with a true consideration of how they feel and function. Strategies to help bridge the communication gap could include: better use of time during visits, preparing for the consultation, a more understandable lay language used by the doctor, a dedicated nurse., 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.)

Host factors that mediate Leishmania genetic exchange are not well defined. Here we demonstrate that natural IgM (IgMn) 1-4 antibodies mediate parasite genetic exchange by inducing the transient formation of a spherical parasite clump that promotes parasite fusion and hybrid formation. We establish that IgMn from Leishmania-free animals binds to the surface of Leishmania parasites to induce significant changes in the expression of parasite transcripts and proteins. Leishmania binding to IgMn is partially lost after glycosidase treatment, although parasite surface phosphoglycans, including lipophosphoglycan, are not required for IgMn-induced parasite clumping. Notably, the transient formation of parasite clumps is essential for Leishmania hybridization in vitro. In vivo, we observed a 12-fold increase in hybrid formation in sand flies provided a second blood meal containing IgMn compared with controls. Furthermore, the generation of recombinant progeny from mating hybrids and parental lines were only observed in sand flies provided with IgMn. Both in vitro and in vivo IgM-induced Leishmania crosses resulted in full genome hybrids that show equal patterns of biparental contribution. Leishmania co-option of a host natural antibody to facilitate mating in the insect vector establishes a new paradigm of parasite-host-vector interdependence that contributes to parasite diversity and fitness by promoting genetic exchange., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC., Patients and Methods: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed., Results: Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose)., Conclusions: Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated., Clinicaltrials.gov Identifier: NCT03499353., (© The Author(s) 2023. Published by Oxford University Press.)

Membrane fouling significantly reduces membrane permeability, leading to higher operational expenses. In situ monitoring of membrane fouling can potentially be used to reduce operation cost by optimizing operational parameters and cleaning conditions. In this study, a platinum wire with a diameter of 20 µm was attached to the surface of a ceramic ultrafiltration membrane, and by measuring the voltage across the wire while applying an AC current, the amplitude of the third harmonic wave, the so-called 3ω signal, was obtained. Results showed increasing 3ω signals during formation of fouling layers, which correlates directly to the hydraulic resistance of the formed fouling layer in semi-dead end filtration of polymeric core shell particles and crossflow filtration of diluted milk. This is explained by the insulating effect of the fouling layers which reduces heat convection by crossflow and the different thermal conductivity in the fouling layer compared with the feed. After membrane cleaning, the permeability and the magnitude of the 3ω signal were partly restored, showing that the 3ω method can be used to monitor the effect of cleaning. The frequency of the AC current was varied so it was possible to measure the heat conductivity in the fouling layer (high frequency) and heat convection due to cross-flow (low frequency). This may potentially be used to get information of the type of fouling (heat conductivity) and thickness of the fouling layer (AC frequency where heat conductivity becomes dominating)., (© 2023. Springer Nature Limited.)

Competing Interests: The idea for this collaborative global response was born at the inaugural meeting of the EULAR study group for Reproductive Health and Family Planning in Milan in June, 2023. We would like to thank Kirsten Frøhlich (Danish Centre for Expertise in Rheumatology (CeViG), Danish Hospital for Rheumatic Diseases, Sonderborg, Denmark) for her immense logistic support throughout the process of this work. CN-P reports consultancy fees from Sanofi Aventis and UCB; speakers fees from UCB, Sanofi and Otsuka; is a medical advisor (medical advisory board) for the pregnancy sickness support charity; and a patron of the Lauren Page Trust. RJEMD reports grants from Galapagos and UCB; speakers fees from Galapagos, Eli Lilly, Novartis, and UCB; support for attending meetings from UCB; and participation on advisory boards for Galapagos and UCB. MM reports consulting fees from GSK, Eli Lilly, and AstraZeneca; speaker fees from UCB, Eli Lilly, AstraZeneca, GSK, Janssen, and AbbVie; participation on an advisory board for Idorsia; and has received Anifrolumab from AstraZeneca for compassionate use. RF-B reports consulting fees from AbbVie, Otsuka, and UCB; and speakers fees from Biogen, Bristol Myers Squibb, GSK, MSD, Novartis, Sanofi, and UCB. AM reports consulting fees from AbbVie, Biogen, Bristol Myers Squibb, MSD, Novartis, Janssen, Eli Lilly, Pfizer, Amgen, UCB, Gilead, Galapagos; speakers fees from AbbVie, Biogen, Bristol Myers Squibb, MSD, Novartis, Janssen, Eli Lilly, Pfizer, Amgen, UCB, Gilead, Galapagos; and support for attending meetings from AbbVie, Novartis, Galapagos, UCB, Janssen. AT reports speakers fees from GSK and UCB, and participation on advisory boards for Galapagos and UCB. BLB reports royalties from Up To Date and is a member of the data safety monitoring committee for the Stop Bloq study. MEBC reports grants from GSK and UCB and consulting fees from UCB. CC reports research support form Amgen, AstraZeneca, GSK, Janssen, Pfizer, Regeneron, Hoffman La-Roche-Genentech, Genzyme Sanofi-Aventis, Takeda Pharmaceutical Company, Sanofi, UCB, Leo Pharma, Sun Pharma Global FZE, Gilead, Novartis, and the Gerber Foundation; and Speaker honorarium from the American Academy of Allergy, Asthma & Immunology aunual meeting. JB reports consultancy fees from Related Sciences, GSK, and Bristol Myers Squibb. DA reports speakers fees from Bristol Myers Squibb. LA reports consulting fees from Sanofi. GB reports grants from AstraZeneca and Pfizer; consulting fees from AstraZeneca and Eli Lilly; and speakers fees from Aenorasis, AstraZeneca, GSK, Eli Lilly, Novartis, and SOBI. WB reports grants from UCB; is an advisory board member for UCB; payment for expert testimony; and is a member of data safety monitoring boards for the Lutein and Zeaxanthin in Pregnancy study and the Stop Bloq study. AB reports research grants from SOBI and participation on an advisory board for SOBI. IB reports consulting fees from AstraZeneca; speakers fees from Amgen, AstraZeneca, GSK, Eli Lilly, MSD, Roche, Sanofi Genzyme, and UCB; support for attending meetings from UCB; and is an advisory group member for AstraZeneca. RC reports speakers fees from GSK, AstraZeneca, Celgene, Janssen, Eli Lilly, Pfizer, UCB, Rubió, and Werfen. SAE reports support for attending meetings from Pfizer. GE reports consulting fees from GSK and Otsuka; and speakers fees from GSK, Otsuka, and Boehringer Ingelheim. JF reports speakers fees and support for attending meetings from UCB. RF-S reports consultancy fees, speakers fees, and support for attending meetings from AstraZeneca. BG reports grants from Bristol Myers Squibb, Pfizer, and Sandoz. IG reports speakers’ fees from Otsuka and participation on an advisory board for Novartis. MH reports research grants from AbbVie, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Janssen Biologics BV, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, and Nordforsk; speakers fees from Pfizer, Medac, and Sandoz; and participation on an advisory board for AbbVie. MH has chaired the steering committee of the Danish Rheumatology Quality Registry, which receives public funding from the hospital owners and funding from pharmaceutical companies. MH cochairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis on the basis of secondary data and is partly funded by Novartis. MK is an employee of GSK. RL is an employee of GSK. LFP-G reports consulting fees from Galapagos. MR is a member of the data safety monitoring committee for the Comparison of Step-up and step-down therapeutic strategies in childhood ArthritiS, which is partly supported by Pfizer. AS reports speakers fees from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, MSD, Eli Lilly, Pfizer, Roche, and UCB; and is principle investigator of the German Biologics Register RABBIT, which is supported by grants from AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Hexal, Eli Lilly, MSD, Pfizer, Samsung Bioepis, Sanofi Aventis, Viatris Sante, UCB, and previously Roche. JV reports speakers’ fees from Eli Lilly, Novartis, Sandoz, and AbbVie. All other authors declare no competing interests.

Systemic lupus erythematosus (SLE) is a disease of high unmet therapeutic need. The challenge of accurately measuring clinically meaningful responses to treatment has hindered progress towards positive outcomes in SLE trials, impeding the approval of potential new therapies. Current primary end points used in SLE trials are based on legacy disease activity measures that were neither specifically designed for the clinical trial context, nor developed according to contemporary recommendations for clinical outcome assessments (COAs), such as that substantial patient input should be incorporated into their design. The Treatment Response Measure for SLE (TRM-SLE) Taskforce is a global collaboration of SLE clinician-academics, patients and patient representatives, industry partners and regulatory experts, established to realize the goal of developing a new COA for SLE clinical trials. The aim of this project is a novel COA designed specifically to measure treatment effects that are clinically meaningful to patients and clinicians, and intended for implementation in a trial end point that supports regulatory approval of novel therapeutic agents in SLE. This Consensus Statement reports the first outcomes of the TRM-SLE project, including a structured process for TRM-SLE development., (© 2023. Springer Nature Limited.)

Objective: An approach to estimation of hip displacement on ultrasound (US) images is described. Its accuracy is validated through numerical simulation, an in vitro study with 3-D-printed hip phantoms and pilot in vivo data., Methods: A diagnostic index, migration percentage (MP), is defined by the ratio of acetabulum-femoral head distance to femoral head width. The acetabulum-femoral head distance could be measured directly on hip US images, while the femoral head width was estimated from the diameter of a best-fit circle. Simulation was performed to evaluate the accuracy of circle fitting with noiseless and noisy data. Surface roughness was also considered. Nine hip phantoms (three different sizes of femur head × three MP values) and 10 US hip images were used in this study., Results: The maximum diameter error was 16.1 ± 8.5% when the roughness and noise were 20% of the original radius and 20% of the wavelet peak, respectively. In the phantom study, the percentage errors of MPs between the 3-D-design US and X-ray US were 0.3%-6.6% and 0.0%-5.7%, respectively. From the pilot clinical trial, the mean absolute difference between the X-ray-US MPs was 3.5 ± 2.8% (1%-9%)., Conclusion: This study indicates that the US method can be used to evaluate hip displacement in children., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Interoception plays a vital role in human cognition and emotion and is an increasingly important part of clinical studies of mind-body approaches and mental health. Interoceptive awareness (IA) encompasses numerous mind-body components and can be assessed by employing a self-report measure such as the Multidimensional Assessment of Interoceptive Awareness (MAIA), which has been adapted and validated across several countries and is used in experimental and clinical settings. In this study, the MAIA-2, which was developed due to the psychometric shortages of MAIA, was thoroughly translated, and its psychometric features were examined in a sample of 306 Norwegian-speaking participants (81% females, ages 16 through 66 plus)., Methods: The participants completed the MAIA-2 Norwegian version (MAIA-2-N) and the COOP/WONCA Functional Assessment Charts measuring psychological, physical, and overall health. The following psychometric qualities of the MAIA-2 were investigated: factor structure, internal consistency, and the moderating role of gender., Results: Confirmatory Factor Analysis (CFA) revealed that an 8-factor model of MAIA-2-N provided the best fit. Also, a bifactor model revealed a proper fit. Good internal consistency and a moderating role of gender, age, and education on the relationships between certain MAIA-2-N factors and health were observed., Conclusions: The MAIA-2-N is an adequate measure of IA in Norwegian-speaking individuals. The factor-structure corresponds with the original MAIA-2 and it shows good internal consistency. Some moderating effects of gender were observed, particularly related to the relationship between IA and physical and psychological state, with the physical state/fitness more closely linked to IA in males and psychological state in females., (© 2023. The Author(s).)

Community-based physical activity opportunities have been shown to help adults with physical disabilities improve their participation in daily activities and reduce social isolation. Despite the known benefits, substantial barriers and challenges inhibit accessibility to these physical activity opportunities. To facilitate the co-construction of strategies to overcome accessibility issues pertaining to community-based physical activity opportunities. In total, 45 individuals with physical disabilities, patients at a rehabilitation hospital, staff members of disability organizations, staff of local or provincial government agencies/departments, kinesiologists, occupational therapists, graduate students, and peer mentors participated in one of four World Cafés held in their respective cities. World Café is a methodology for fostering collaborative, solution-focused conversation that aims to solve problems through collective intelligence. Participants were divided into groups of three to four people and invited to engage in evolving rounds of discussions responding to prompts about accessibility to physical activity in their communities. Transcripts were analyzed using content analysis. In total, 17 strategies were identified, addressing 5 areas: representation and visibility (e.g., prioritize hiring people with a disability), finances (e.g., reduce direct costs for participants), connection and social support (e.g., foster social networks that provide informational support), education and programming (e.g., enhance awareness of existing services and resources), and government programs and policies (e.g., enforce accessibility standards for indoor and outdoor spaces). The findings of this study provide strategies and practical applications for community programs and governments to consider for increasing access to physical activity opportunities for people with physical disabilities., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Understanding spinal cord assembly is essential to elucidate how motor behavior is controlled and how disorders arise. The human spinal cord is exquisitely organized, and this complex organization contributes to the diversity and intricacy of motor behavior and sensory processing. But how this complexity arises at the cellular level in the human spinal cord remains unknown. Here we transcriptomically profiled the midgestation human spinal cord with single-cell resolution and discovered remarkable heterogeneity across and within cell types. Glia displayed diversity related to positional identity along the dorso-ventral and rostro-caudal axes, while astrocytes with specialized transcriptional programs mapped into white and gray matter subtypes. Motor neurons clustered at this stage into groups suggestive of alpha and gamma neurons. We also integrated our data with multiple existing datasets of the developing human spinal cord spanning 22 weeks of gestation to investigate the cell diversity over time. Together with mapping of disease-related genes, this transcriptomic mapping of the developing human spinal cord opens new avenues for interrogating the cellular basis of motor control in humans and guides human stem cell-based models of disease., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL., Method: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion., Results: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04)., Conclusion: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups., Trial Registration: ClinicalTrials.gov Identifier: NCT04766060., (© 2023. The Author(s).)

Background: Telemedicine holds a potential to strengthen self-management support outside health care settings in the everyday management of type 1 diabetes (T1D). However, existing effectiveness reviews are older or include a relatively narrow focus on specific definitions of telemedicine or included databases., Objective: To conduct a systematic review of the effectiveness of telemedicine solutions versus any comparator on diabetes-related outcomes among people with T1D., Methods: Studies including adults (≥18 years) with T1D published before October 14, 2020, were eligible. Primary outcome was glycated hemoglobin (HbA1c, %). The Cochrane Library, PubMed, EMBASE, and CINAHL were searched. Meta-analysis based on the mean difference in HbA1c% was used to pool effects. The Cochrane tool was applied to assess risk-of-bias, and the certainty of evidence was graded using the GRADE approach., Results: A total of 22 studies were included (with 1615 participants). Treatment effect for HbA1c% favored telemedicine (mean difference of -0.26% [95% confidence interval:-0.37% to -0.15%]) with moderate effect certainty. Heterogeneity was moderate ( I 2 = 33.30%). Although not significant, secondary outcomes were all in favor of telemedicine except number of severe hypoglycemic events and diabetes knowledge, but the certainty of the evidence for those outcomes was all low or very low., Discussion: Reducing average HbA1c% levels are important to combat the risk of diabetic complications and premature death. However, the evidence mostly consist of small studies with a relative short duration and the estimated pooled effect is smaller than could be expected from quality improvement strategies in general for diabetes management., Prospero Number: CRD42020123565.

Aim: To identify possible early biomarkers that could predict later functional capabilities in children at risk for cerebral palsy (CP)., Methods: Data from 869 term children with CP were extracted from the Canadian Cerebral Palsy Registry. Univariate analyses were conducted to measure the association between readily available objective early biomarkers (neonatal encephalopathy [NE], cord or first hour of life pH, magnetic resonance imaging [MRI]) and functional outcomes such as mobility and feeding status. Multivariable regressions were then modeled to study whether adding predictors would affect the strength of the observed association., Results: Patients with NE have higher odds of having an assigned Gross Motor Function Classification Score level of IV to V (prevalence ratio [PR], 2.87; 95% confidence interval [CI], 2.07 to 3.97) and are more likely to require dependent tube feeding (PR, 2.09; 95% CI, 1.12 to 3.88); this was similarly seen in patients with MRI findings of deep gray matter injury, watershed injury, near-total brain injury, and/or cortical malformation (mobility status [PR, 5.13; 95% CI, 3.73 to 7.11] and feeding status [PR, 4.87; 95% CI, 2.57 to 9.75]). Patients with cord or first hour of life pH <7 were also more likely to predict dependent mobility status (PR, 2.86; 95% CI, 1.76 to 4.69), however, not significantly more likely to predict eventual dependent feeding status (PR, 1.47; 95% CI, 0.58 to 3.32)., Conclusions: This retrospective cohort study demonstrates that NE, MRI findings and cord or first hour of life pH can reliably predict later CP related functioning. These associations can be used to inform and clarify early prognosis discussions between caregivers and health professionals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.