Search

When observing other people during naturally paced and dynamic interactions, it is essential to look at specific locations at the right time to extract a maximum of socially informative content. In this study, we aimed to investigate the looking behavior of typically developing toddlers and toddlers later diagnosed with autism when observing other children interact. The sample consisted of 98 toddlers; 22 in a low-likelihood of autism group, 60 in an elevated likelihood of autism group who did not receive a subsequent diagnosis, and 16 in an elevated likelihood group who did receive an autism diagnosis. Participants performed an eye tracking task at 18 months of age and were assessed for diagnostic outcome at 36 months. The video stimuli consisted of two children interacting, where a boy reaches out for a toy and a girl refuses to give it to him. The low likelihood group showed an expected increase in ratio of looking at the girl's face after the boy requested the toy, as compared to before (t(21) = -3.337, p = 0.003). Toddlers with later autism showed a significantly lower ratio of looking at the girl's face during this time window, as compared to the other groups (F(2,91) = 3.698, p = 0.029). These findings provide new leads on how social gaze may be different in children with autism in everyday life (e.g., kindergarten), and highlight the need of studying the dynamics of gaze on short time scales.

The purpose of the current study was to use the infant sibling design to explore whether proband traits of autism and ADHD could provide information about their infant sibling's temperament. This could help us to gain information about the extent to which infant temperament traits are differentially associated with autism and ADHD traits. We used parent-ratings of autistic traits and ADHD traits (CRS-3) in older siblings diagnosed with autism (age range 4 to 19 years), and their infant siblings' temperament traits (IBQ) at 9 months of age in 216 sibling pairs from two sites (BASIS, UK, and EASE, Sweden) to examine associations across siblings. We found specific, but modest, associations across siblings after controlling for sex, age, developmental level and site. Proband autistic traits were specifically related to low levels of approach in the infant siblings, with infant developmental level explaining part of the variance in infant approach. Proband ADHD traits were specifically related to high levels of infant activity even after controlling for covariates. Our findings suggest that proband traits of autism and ADHD carry information for infant sibling's temperament, indicating that inherited liability may influence early emerging behaviours in infant siblings. The impact of sex, age, developmental level and site are discussed.

Being looked at is an important communicative signal, and attenuated responses to such direct gaze have been suggested as an early sign of autism. Using live eye tracking, we examined whether direct gaze elicits different gaze responses in infants at ages 10, 14 and 18 months with and without later autism in real-life interaction. The sample consisted of 169 infants: 35 with elevated likelihood of autism and subsequent diagnosis, 94 without subsequent diagnosis and 40 with typical likelihood of autism. Infants in all groups tended to look more towards the adult's face shortly after the direct gaze occurred. Neither how much nor how quickly the infants responded to the direct gaze differentiated the without elevated likelihood of autism and subsequent diagnosis and with elevated likelihood of autism and subsequent diagnosis groups. Infants in the typical likelihood group looked more at the face after the direct-gaze event than infants in the two elevated likelihood groups, but this result is tentative. In an exploratory analysis, infants in the elevated likelihood of autism and subsequent diagnosis group looked away quicker from faces with direct gaze than infants in the typical likelihood group, but this measure did not correlate with dimensional autism or differentiate between the two elevated likelihood groups. The current results suggest that attenuated behavioural responses to direct gaze in infancy are neither strong nor specific early markers of autism.

Abstract Abstract The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1−/−) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE−/−/ASGR1−/− mice presented lower plasma cholesterol and triglyceride levels compared to ApoE−/−. This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE−/−/ASGR1−/− mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE−/−/ASGR1−/− mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders. Graphical abstract

Abstract Background Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various somatic manifestations and cognitive impairments, but the latter are sparsely described in adults. This study aimed at characterizing potential impairments of neurocognitive functions using neuropsychological tests as well as a self-report questionnaire. Methods In a nationwide, population-based study including 103 adults with NF1 and 38 age- and gender-matched NF1-free comparisons, we used a comprehensive neurocognitive test battery to assess intelligence and visual short-term memory, immediate visuospatial recall, reaction time, sustained attention, motor speed, planning, planning time, working memory as well as multitasking and a questionnaire to assess executive functions. Descriptive statistics, multivariate analysis of variance (MANOVA), and general linear models with repeated measure analysis of variance (ANOVA) were used. Results We observed a statistically significant difference in overall performance-based cognitive functioning. Adults with NF1 showed significant, moderate-to-severe impairments in intelligence, visual short-term memory, immediate visuospatial recall, sustained attention (p

Abstract Novel treatments in multiple myeloma (MM) could influence the incidence of skeletal‐related events (SREs). We aimed to examine the incidence of SRE and the preventive use of osteoclast inhibitors (OIs) in a cohort of MM patients in the era of modern treatment. In this real‐world retrospective study, we included 199 patients with a diagnosis of MM between January 1, 2010, and December 31, 2019, with follow‐up at St. Olavs University Hospital. Data was extracted from The Myeloma Registry of Central Norway. SREs occurred in 46% of patients at baseline and 55.8% during follow‐up. Excluding baseline SREs, the incidence rate was 29 (95% confidence interval: 26–33) per 100 person years. 48% experienced > 1 SRE. The incidence of SREs was highest at baseline followed by a gradual increase in each subsequent line of treatment. The first two years after diagnosis 80% received bisphosphonates (BPs). The proportion of recommended dosage was 46%. Only two cases (1.2%) of symptomatic hypocalcemia and one case (0.6%) of osteonecrosis of the jaw were identified. SREs are still a common problem in an era of novel treatment. Cumulative dosage of BPs was lower than recommended, and treatment with BPs was safe in this population.

The Barents Sea, an important component of the Arctic Ocean, is experiencing changes in its ocean currents, stratification, sea ice variability, and marine ecosystems. Inflowing Atlantic Water (AW) is a key driver of these changes. As AW predominantly enters the Barents Sea via the Barents Sea Opening, other pathways remain relatively unexplored. Comparisons of summer climatology fields of temperature from the last century with those from 2000–2019 indicate warming in the Storfjordrenna trough and along two shallow banks, Hopenbanken and Storfjordbanken, within the Svalbard Archipelago. Additionally, they indicate shoaling of AW that extends further into the “channel” between the islands of Edgeøya and Hopen. This region emerges as a pathway enabling AW to enter the northwestern Barents Sea. Moreover, 1-year-long records from a mooring deployed between September 2018 and November 2019 at the saddle of this channel show the flow of Atlantic-origin waters into the Arctic domain of the northwestern Barents Sea. The average current is directed eastwards into the Barents Sea and exhibits significant variability throughout the year. Here, we investigate this variability on timescales ranging from hours to months. Wind forcing mediates currents, water exchange, and heat exchange through the channel by driving geostrophic adjustment to Ekman transport. The main drivers of the warm-water inflow and across-saddle transport of positive temperature anomalies include persistently strong semidiurnal tidal currents, intermittent wind-forced events, and wintertime warm-water intrusions forced by upstream conditions. We propose that similar topographic constraints near AW pathways may become more important in the future. Ongoing warming and shoaling of AW, coupled with changes in large-scale weather patterns, are likely to increase warm-water inflow and heat transport through the processes identified in this study.

Abstract Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have the capacity to delay viral rebound when administered to people with HIV-1 (PWH) during anti-retroviral therapy (ART) interruption. To further enhance the performance of bNAbs through their Fc effector functions, in particular NK cell-mediated killing of HIV-1 infected cells, we have produced a panel of glyco-engineered (afucosylated) bNAbs with enhanced affinity for Fc gamma receptor IIIa. These afucosylated anti-HIV-1 bNAbs enhance NK cell activation and degranulation compared to fucosylated counterparts even at low antigen density. NK cells from PWH expressing exhaustion markers PD-1 and TIGIT are activated in a similar fashion by afucosylated bNAbs as NK cell from HIV-1 negative individuals. Killing of HIV-1 infected cells is most effective with afucosylated bNAbs 2G12, N6, PGT151 and PGDM1400, whereas afucosylated PGT121 and non-neutralizing antibody A32 only induce minor NK cell-mediated killing. These data indicate that the approach angle and affinity of Abs influence the capacity to induce antibody-dependent cellular cytotoxicity. Thus, afucosylated bNAbs have the capacity to induce NK cell-mediated killing of infected cells, which warrants further investigation of afucosylated bNAb administration in vivo, aiming for reduction of the viral reservoir and ART free durable control.

Introduction One-third of adults aged 65+ fall annually. Injuries from falls can be devastating for individuals and account for 1.5% of annual healthcare spending. With the growing ageing population, falls place increased strain on scarce health resources. Prevention strategies that target individuals at high risk for falls demonstrate the best value for money; however, limited efficiency (ie, cost-effectiveness) information for fall prevention interventions hinders the implementation of effective falls prevention programmes. Living systematic reviews provide a timely up-to-date evidence-based resource to inform clinical guidelines and health policy decisions. This protocol details the methodology for a living systematic review of the efficiency (ie, cost-effectiveness) of fall prevention interventions for older adults in three settings: community-dwelling, aged care and hospitals.Methods and analysis This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Peer-reviewed economic evaluations of controlled clinical trials or health state models will be included. Reports will be obtained through monthly systematic searches of CENTRAL (Ovid), CINAHL (EBSCO), Embase (Ovid), MEDLINE (Ovid), SCOPUS (Elsevier) and Web of Science (Clarivate) alongside snowballing and handsearching EconLit and the Tufts Cost Effectivness Analysis Registry. Screening, data extraction, quality assessment and risk of bias will be assessed by multiple reviewers. The primary outcomes will be the incremental cost-effectiveness (ie, incremental cost per fall prevented), incremental cost-utility (ie, incremental cost per quality-adjusted life year gained) or cost-benefit ratio. Additional outcomes will include falls and cost-related measures. All economic outcomes will be reported in a common year and currency. Results will be reported as a narrative synthesis; meta-analysis will be considered based on data quality, suitability and availability.Ethics and dissemination Ethical approval is not required as primary human data will not be collected. Results will be disseminated through peer-reviewed publications and a dedicated website.PROSPERO registration number CRD42024532485.

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

Abstract This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

The ability to perceive approximate numerosity is present in many animal species, and emerges early in human infants. Later in life, it is moderately heritable and associated with mathematical abilities, but the etiology of the Approximate Number System (ANS) and its degree of independence from other cognitive abilities in infancy is unknown. Here, we assessed the phenotypic specificity as well as the influence of genetic and environmental factors on the ANS in a sample of 5-month-old twins (N = 514). We found a small-to-moderate but statistically significant effect of genetic factors on ANS acuity (heritability = 0.18, 95% CI: 0.02, 0.33), but only when differences in numerosity were relatively large (1:4 ratio). Non-verbal ability assessed with the Mullen Scales of Early Learning (MSEL) was found to be heritable (0.47; 95% CI: 0.34, 0.57) and the phenotypic association between ANS acuity and non-verbal ability performance was close to zero. Similarly, we found no association between ANS acuity and general attention during the task. An unexpected weak but statistically significant negative association between ANS acuity and scores on the receptive language scale of the MSEL was found. These results suggest that early ANS function may be largely independent from other aspects of non-verbal development. Further, variability in ANS in infancy seems to, to some extent, reflect genotypic differences in the population.

Abstract Background Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics. Methods A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Results Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers. Conclusion This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors.

Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases.

Abstract Introduction Transitioning to adulthood often involves achieving independence from the parental home. We assessed whether the likelihood of leaving the parental home, cohabitation, and marriage was similar between patients who experienced a hematologic malignancy at a young age and their peers. Methods We identified 11,575 patients diagnosed with a hematologic malignancy under the age of 20 years between 1971 and 2011 in Denmark, Finland, and Sweden, 57,727 country‐, age‐, and sex‐matched population comparisons and 11,803 sibling comparisons and obtained annual information on family and marital status by linking to the statistical institute databases. Hazard ratios (HR) for leaving the parental home, cohabitation and marriage were estimated using Cox proportional hazards modeling. Results Young adults with a history of a hematologic malignancy were slightly less likely to leave the parental home (HR 0.89; 95% confidence interval [CI] 0.86–0.92; HR 0.87 [95% CI 0.82–0.92]), cohabit with a nonmarital partner (HR 0.83 [95%CI 0.78–0.87]; HR 0.84 [95% CI 0.77–0.92]) and be married (HR 0.87 [95% CI 0.82–0.91]; HR 0.86 [95% CI 0.79–0.93]), compared with population comparisons and siblings, respectively. Conclusions Our findings provide reassurance that young adults with a history of a hematologic malignancy show only a slight decrease in their likelihood of gaining independence from their childhood family and forming close interpersonal relationships compared to peers. While most patients are coping well in the long term, integrating structured psychosocial support into long‐term follow‐up is recommended to facilitate a timely and adequate transition into adulthood.

Abstract A tendency to look at the left side of faces from the observer’s point of view has been found in older children and adults, but it is not known when this face-specific left gaze bias develops and what factors may influence individual differences in gaze lateralization. Therefore, the aims of this study were to estimate gaze lateralization during face observation and to more broadly estimate lateralization tendencies across a wider set of social and non-social stimuli, in early infancy. In addition, we aimed to estimate the influence of genetic and environmental factors on lateralization of gaze. We studied gaze lateralization in 592 5-month-old twins (282 females, 330 monozygotic twins) by recording their gaze while viewing faces and two other types of stimuli that consisted of either collections of dots (non-social stimuli) or faces interspersed with objects (mixed stimuli). A right gaze bias was found when viewing faces, and this measure was moderately heritable (A = 0.38, 95% CI 0.24; 0.50). A left gaze bias was observed in the non-social condition, while a right gaze bias was found in the mixed condition, suggesting that there is no general left gaze bias at this age. Genetic influence on individual differences in gaze lateralization was only found for the tendency to look at the right versus left side of faces, suggesting genetic specificity of lateralized gaze when viewing faces.