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When we perceive other people in our everyday encounters their bodies are often partially occluded. High-level visual areas are known to automatically complete partially occluded objects, as revealed by the classic “gestalt” phenomena. However, here we set out to investigate if “body gestalt” completion is “embodied” and not purely visual. Human observers might intuitively map their own body knowledge onto partially occluded others and thereby complete their “body gestalt” by means of posture and/or motor resonance. To this end we developed new stimuli showing a face and two hands that could either form a “body gestalt” or not. Our most important finding across five behavioural experiments was that body gestalt completion was not solely based on visual features like the classic gestalt phenomena. Responses were significantly faster when the observer's posture matched the configuration of face and hands shown on screen then. In this sense body gestalt completion is an embodied process, where humans intuitively use their own body knowledge to ‘fill in the gaps’ in a body stimulus. We further conclude that in our particular paradigm posture resonance was apparently more important for body gestalt completion than motor resonance—with the former being most likely mediated by proprioceptive body schema representations, while the latter by the mirror neuron system. Finally, we will also present preliminary analysis of MEG data. Our findings elucidate the mechanisms of how humans perceive others holistically and how they might implicitly align themselves in everyday social interactions to facilitate an optimal co-representation of each other.

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.

Summary: Background: Accurate prediction of seizures can help to direct resource-intense continuous electroencephalogram (CEEG) monitoring to neonates at high risk of seizures. We aimed to use data from standardised EEG reports to generate seizure prediction models for vulnerable neonates. Methods: In this retrospective cohort study, we included neonates who underwent CEEG during the first 30 days of life at the Children's Hospital of Philadelphia (Philadelphia, PA, USA). The hypoxic ischaemic encephalopathy subgroup included only patients with CEEG data during the first 5 days of life, International Classification of Diseases, revision 10, codes for hypoxic ischaemic encephalopathy, and documented therapeutic hypothermia. In January, 2018, we implemented a novel CEEG reporting system within the electronic medical record (EMR) using common data elements that incorporated standardised terminology. All neonatal CEEG data from Jan 10, 2018, to Feb 15, 2022, were extracted from the EMR using age at the time of CEEG. We developed logistic regression, decision tree, and random forest models of neonatal seizure prediction using EEG features on day 1 to predict seizures on future days. Findings: We evaluated 1117 neonates, including 150 neonates with hypoxic ischaemic encephalopathy, with CEEG data reported using standardised templates between Jan 10, 2018, and Feb 15, 2022. Implementation of a consistent EEG reporting system that documents discrete and standardised EEG variables resulted in more than 95% reporting of key EEG features. Several EEG features were highly correlated, and patients could be clustered on the basis of specific features. However, no simple combination of features adequately predicted seizure risk. We therefore applied computational models to complement clinical identification of neonates at high risk of seizures. Random forest models incorporating background features performed with classification accuracies of up to 90% (95% CI 83–94) for all neonates and 97% (88–99) for neonates with hypoxic ischaemic encephalopathy; recall (sensitivity) of up to 97% (91–100) for all neonates and 100% (100–100) for neonates with hypoxic ischaemic encephalopathy; and precision (positive predictive value) of up to 92% (84–96) in the overall cohort and 97% (80–99) in neonates with hypoxic ischaemic encephalopathy. Interpretation: Using data extracted from the standardised EEG report on the first day of CEEG, we predict the presence or absence of neonatal seizures on subsequent days with classification performances of more than 90%. This information, incorporated into routine care, could guide decisions about the necessity of continuing EEG monitoring beyond the first day, thereby improving the allocation of limited CEEG resources. Additionally, this analysis shows the benefits of standardised clinical data collection, which can drive learning health system approaches to personalised CEEG use. Funding: Children's Hospital of Philadelphia, the Hartwell Foundation, the National Institute of Neurological Disorders and Stroke, and the Wolfson Foundation.

Abstract Fruit bats (Family: Pteropodidae) are animals of great ecological and economic importance, yet their populations are threatened by ongoing habitat loss and human persecution. A lack of ecological knowledge for the vast majority of Pteropodid species presents additional challenges for their conservation and management. In Australia, populations of flying‐fox species (Genus: Pteropus) are declining and management approaches are highly contentious. Australian flying‐fox roosts are exposed to management regimes involving habitat modification, through human–wildlife conflict management policies, or vegetation restoration programs. Details on the fine‐scale roosting ecology of flying‐foxes are not sufficiently known to provide evidence‐based guidance for these regimes, and the impact on flying‐foxes of these habitat modifications is poorly understood. We seek to identify and test commonly held understandings about the roosting ecology of Australian flying‐foxes to inform practical recommendations and guide and refine management practices at flying‐fox roosts. We identify 31 statements relevant to understanding of flying‐fox roosting structure and synthesize these in the context of existing literature. We then contribute a contemporary, fine‐scale dataset on within‐roost structure to further evaluate 11 of these statements. The new dataset encompasses 13‐monthly repeat measures from 2,522 spatially referenced roost trees across eight sites in southeastern Queensland and northeastern New South Wales. We show evidence of sympatry and indirect competition between species, including spatial segregation of black and grey‐headed flying‐foxes within roosts and seasonal displacement of both species by little red flying‐foxes. We demonstrate roost‐specific annual trends in occupancy and abundance and provide updated demographic information including the spatial and temporal distributions of males and females within roosts. Insights from our systematic and quantitative study will be important to guide evidence‐based recommendations on restoration and management and will be crucial for the implementation of priority recovery actions for the preservation of these species in the future.

The black flying fox (Pteropus alecto) is a natural reservoir for Hendra virus, a paramyxovirus that causes fatal infections in humans and horses in Australia. Increased excretion of Hendra virus by flying foxes has been hypothesized to be associated with physiological or energetic stress in the reservoir hosts. The objective of this study was to explore the leukocyte profiles of wild-caught P. alecto, with a focus on describing the morphology of each cell type to facilitate identification for clinical purposes and future virus spillover research. To this end, we have created an atlas of images displaying the commonly observed morphological variations across each cell type. We provide quantitative and morphological information regarding the leukocyte profiles in bats captured at two roost sites located in Redcliffe and Toowoomba, Queensland, Australia, over the course of two years. We examined the morphology of leukocytes, platelets, and erythrocytes of P. alecto using cytochemical staining and characterization of blood films through light microscopy. Leukocyte profiles were broadly consistent with previous studies of P. alecto and other Pteropus species. A small proportion of individual samples presented evidence of hemoparasitic infection or leukocyte morphological traits that are relevant for future research on bat health, including unique large granular lymphocytes. Considering hematology is done by visual inspection of blood smears, examples of the varied cell morphologies are included as a visual guide. To the best of our knowledge, this study provides the first qualitative assessment of P. alecto leukocytes, as well as the first set of published hematology reference images for this species.

Abstract Background Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192–197). Methods Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. Results The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. Limitations In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. Conclusion Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

The hydromorphological analysis (HMA) is a method to quantify the potentials of mire revitalisation. In this study, the HMA is combined with the new peatland-tool of the water balance model AKWA-M®. This peatland-tool includes as well depth functions of the hydraulic conductivity and drainable porosity for several mire-ecotope-types as specific equations for mire evapotranspiration. The calculations were applied in several peatlands and mires of the German-Czech Ore Mountains (Erzgebirge/Krušné hory). The simulation results show that the chosen depth functions are valuable for the water balance calculation of mire ecotopes with a fully developed akrotelm like ombro- and mesotrophic peatlands. For degenerated peat soil or regenerating mires it is necessary to improve the model and the parameter calibration, especially the depth functions, with additional measured data in different peatlands.

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) ( C. asiatica ) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS.

Introduction: Effects and interactions between different spaceflight stressors are expected to be experienced by crew on missions when exposed to microgravity and galactic cosmic rays (GCRs). One of the limitations of previous studies on simulated weightlessness using hindlimb unloading (HU) is that a control HU condition was not included., Methods: We characterized the behavioral performance of male Fischer rats 2 months after sham or total body irradiation with a simplified 5-ion 6-mixed-beam exposure representative of GCRs in the absence or presence of HU. Six months later, the plasma, hippocampus, and cortex were processed to determine whether the behavioral effects were associated with long-term alterations in the metabolic pathways., Results: In the open field without and with objects, interactions were observed for radiation × HU. In the plasma of animals that were not under the HU or control HU condition, the riboflavin metabolic pathway was affected most for sham irradiation vs. 0.75 Gy exposure. Analysis of the effects of control HU on plasma in the sham-irradiated animals showed that the alanine, aspartate, glutamate, riboflavin, and glutamine metabolisms as well as arginine biosynthesis were affected. The effects of control HU on the hippocampus in the sham-irradiated animals showed that the phenylalanine, tyrosine, and tryptophan pathway was affected the most. Analysis of effects of 0.75 Gy irradiation on the cortex of control HU animals showed that the glutamine and glutamate metabolic pathway was affected similar to the hippocampus, while the riboflavin pathway was affected in animals that were not under the control HU condition. The effects of control HU on the cortex in sham-irradiated animals showed that the riboflavin metabolic pathway was affected. Animals receiving 0.75 Gy of irradiation showed impaired glutamine and glutamate metabolic pathway, whereas animals receiving 1.5 Gy of irradiation showed impaired riboflavin metabolic pathways. A total of 21 plasma metabolites were correlated with the behavioral measures, indicating that plasma and brain biomarkers associated with behavioral performance are dependent on the environmental conditions experienced., Discussion: Phenylalanine, tyrosine, and tryptophan metabolism as well as phenylalanine and tryptophan as plasma metabolites are biomarkers that can be considered for spaceflight as they were revealed in both Fischer and WAG/Rij rats exposed to simGCRsim and/or HU., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Raber, Chaudhari, De la Torre, Holden, Kessler, Glaeser, Lenarczyk, Leonard, Borg, Kwok, Patel, Kronenberg, Olsen, Willey, Morré, Choi, Stevens, Bobe, Minnier and Baker.)

Lay Abstract: Many autistic individuals report difficulties in social situations, where they are required to think about what goes on in others' minds. These states of the mind can include how others perceive the world around them, their beliefs, or their desires. While research has shown that autistic children could be delayed in developing their full capacity in this regard, less is known about how adults process others' experiences and beliefs. Here we used a novel task and asked adults to participate online. Participants self-reported whether they had been diagnosed with autism or not and we split them into two groups depending on their response. We also asked participants to fill in a self-report questionnaire about social preferences and habits and we also asked them to conduct a test of their nonverbal reasoning ability. Importantly, the autistic and the non-autistic groups did not differ in their nonverbal reasoning abilities, and on our task, we observed that the autistic group committed fewer mistakes than the non-autistic group. Autistic participants were particularly fast and made fewer mistakes on those responses that overlapped with their own view and belief of reality. In conclusion, our findings do not support a simple view of autism in terms of deficits in either social or more general thinking abilities. Instead, autistic adults might favour slightly different ways of thinking about other's experiences and beliefs that is more firmly linked to their own experience and knowledge.

Paediatric autoimmune encephalitis, including acute disseminated encephalomyelitis, are inflammatory brain diseases presenting with cognitive deficits, psychiatric symptoms, seizures, MRI and EEG abnormalities. Despite improvements in disease recognition and early immunotherapy, long-term outcomes in paediatric autoimmune encephalitis remain poor. Our aim was to understand functional connectivity changes that could be associated with negative developmental outcomes across different types of paediatric autoimmune encephalitis using magnetoencephalography. Participants were children diagnosed with paediatric autoimmune encephalitis at least 18 months before testing and typically developing children. All completed magnetoencephalography recording at rest, T 1 MRI scans and neuropsychology testing. Brain connectivity (specifically in delta and theta) was estimated with amplitude envelope correlation, and network efficiency was measured using graph measures (global efficiency, local efficiency and modularity). Twelve children with paediatric autoimmune encephalitis (11.2 ± 3.5 years, interquartile range 9 years; 5M:7F) and 12 typically developing controls (10.6 ± 3.2 years, interquartile range 7 years; 8M:4F) participated. Children with paediatric autoimmune encephalitis did not differ from controls in working memory ( t (21) = 1.449; P = 0.162; d = 0.605) but had significantly lower processing speed ( t (21) = 2.463; P = 0.023; Cohen's d = 1.028). Groups did not differ in theta network topology measures. The paediatric autoimmune encephalitis group had a significantly lower delta local efficiency across all thresholds tested ( d = -1.60 at network threshold 14%). Theta modularity was associated with lower working memory ( β = -0.781; t (8) = -2.588, P = 0.032); this effect did not survive correction for multiple comparisons ( P (corr) = 0.224). Magnetoencephalography was able to capture specific network alterations in paediatric autoimmune encephalitis patients. This preliminary study demonstrates that magnetoencephalography is an appropriate tool for assessing children with paediatric autoimmune encephalitis and could be associated with cognitive outcomes., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: To prospectively determine the influence of variations of surgical radicality and surgical quality on long-term outcome in patients with stage I-III colon cancer., Methods: From a prospective multicenter cohort study including 1040 patients undergoing surgery for colorectal cancer from 09/2001 to 06/2005 in nine Swiss and one German hospital, 423 patients with stage I-III colon cancer were selected and analyzed. Surgeons and pathologists filled in standardized forms prospectively assessing items of oncosurgical radicality and quality. Patients had standardized follow-up according to national guidelines., Results: Follow-up was median 6.2 years (range 0.3-10.4) showing a 5-year disease-free survival/overall survival of 83 %/87 % in stage I (n = 85), 69 %/77 % in stage II (n = 187), and 53 %/61 % in stage III (n = 151) colon cancer. Despite remarkable variations of oncosurgical radicality and quality, the multivariate model revealed that mainly quality items correlated significantly with disease-free survival (surgical tumor lesion HR 2.12, p = 0.036, perioperative blood transfusion HR 1.67, p = 0.018, emergency resection HR 1.74, p = 0.035) and overall survival (early venous ligation HR 0.66, p = 0.023, surgical tumor lesion HR 2.28, p = 0.027, perioperative blood transfusion HR1.79, p = 0.010, emergency resection HR 1.88, p = 0.026), while radicality parameters (length of specimen, distance of the tumor to nearest bowel resection site, number of lymph nodes, height of resected mesocolon and of central vascular dissection) did not., Conclusion: Surgical quality seems to have a stronger impact on oncologic long-term outcome in stage I - III colon cancer than surgical radicality., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We investigated the neural signatures of expert decision-making in the context of police training in a virtual reality-based shoot/don't shoot scenario. Police officers can use stopping force against a perpetrator, which may require using a firearm and each decision made by an officer to discharge their firearm or not has substantial implications. Therefore, it is important to understand the cognitive and underlying neurophysiological processes that lead to such a decision. We used virtual reality-based simulations to elicit ecologically valid behavior from authorized firearms officers (AFOs) in the UK and matched novices in a shoot/don't shoot task and recorded electroencephalography concurrently. We found that AFOs had consistently faster response times than novices, suggesting our task was sensitive to their expertise. To investigate differences in decision-making processes under varying levels of threat and expertise, we analyzed electrophysiological signals originating from the anterior cingulate cortex. In line with similar response inhibition tasks, we found greater increases in preresponse theta power when participants inhibited the response to shoot when under no threat as compared with shooting. Most importantly, we showed that when preparing against threat, theta power increase was greater for experts than novices, suggesting that differences in performance between experts and novices are due to their greater orientation toward threat. Additionally, shorter beta rebounds suggest that experts were "ready for action" sooner. More generally, we demonstrate that the investigation of expert decision-making should incorporate naturalistic stimuli and an appropriate control group to enhance validity., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Alexander et al.)

What would a theory of visuospatial perspective taking (VSPT) look like? Here, ten researchers in the field, many with different theoretical viewpoints and empirical approaches, present their consensus on the three big questions we need to answer in order to bring this theory (or these theories) closer., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Heterozygous carriers of the glucocerebrosidase 1 (GBA) L444P Gaucher mutation have an increased risk of developing Parkinson's disease (PD). The GBA mutations result in elevated alpha synuclein (aSyn) levels. Heterozygous mice carrying one allele with the L444P mutation knocked-into the mouse gene show increased aSyn levels and are more sensitive to motor deficits following exposure to the neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP than wild-type mice. Paraquat (PQ), a herbicide, increases PD risk in most studies. Its effects on the brain involve alterations in the gut microbiome. Exposure to dextran sulfate sodium (DSS), a mouse model of colitis, can be used to determine whether gut microbiome alterations are sufficient to induce PD-relevant phenotypes. We rederived the A53T-L444P and A53T mouse lines to assess whether PQ, PQ in combination with radiation exposure (IR), and DSS have differential effects in A53T and A53T-L444P mice and whether these effects are associated with alterations in the gut microbiome. PQ and PQ + IR have differential effects in A53T and A53T-L444P mice. In contrast, effects of DSS are only seen in A53T-L444P mice. Exposure and genotype modulate the relationship between the gut microbiome and behavioral performance. The gut microbiome may be an important mediator of how environmental exposures or genetic mutations yield behavioral and cognitive impacts.

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures. Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Raber, Holden, Kessler, Glaeser, McQuesten, Chaudhari, Stenzel, Lenarczyk, Leonard, Morré, Choi, Kronenberg, Borg, Kwok, Stevens, Olsen, Willey, Bobe, Minnier and Baker.)

Abstract: von Willebrand disease (vWD) is an inherited bleeding disorder that is characterized by a quantitative or qualitative deficiency of the von Willebrand factor (vWF). Type 3 is the most severe form of vWD with a near-complete absence of vWF and a significantly increased risk of excessive bleeding and hematoma during a surgical procedure. To date, no data on surgical and hemostatic management of a type 3 vWD patient undergoing body-contouring surgery has been published. We report the case of a 47-year-old woman with type 3 vWD requiring medically indicated abdominoplasty after massive weight loss due to bariatric surgery. The case was successfully managed with individualized bodyweight-adapted substitution of recombinant vWF vonicog alfa and tranexamic acid under close monitoring of vWF and factor VIII activity. For further risk stratification, we propose the multidisciplinary treatment of patients with severe vWF undergoing elective plastic surgery in specialized centers providing around-the-clock laboratory testing and access to a blood bank. In addition, strict hemostasis during surgery and early postoperative mobilization with fitted compression garments are recommended to further reduce the risk of bleeding and thromboembolic complications., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To assess the inter-rater reliability of modified Downes' scores assigned by physicians and nurses in the Ethiopian Neonatal Network and to calculate the concordance of score-based treatment for preterm infants with respiratory distress., Methods: We included preterm infants admitted from June 2020 to July 2021 to four tertiary neonatal intensive care units (NICUs) of the Ethiopian Neonatal Network that presented with respiratory distress. We calculated the kappa statistic to determine the nurse and physician correlation for each component of the modified Downes' score and total score on admission and evaluated the concordance of scores above and below the treatment threshold of 4., Results: Of the 1151 eligible infants admitted, 817 infants (71%) had scores reported concurrently and independently by nurse and physician. The kappa statistic for modified Downes' score components ranged from 0.88 to 0.92 and was 0.89 for the total score. There was 98% concordance for score-based treatment., Conclusion: Incorporation of the modified Downes' score on admission for preterm infants with respiratory distress was feasible in tertiary NICUs in Ethiopia. The kappa statistics showed near-perfect agreement between nurse and physician assessments, translating to a very high degree of concordance in score-based treatment recommendations. These results highlight an opportunity for task-shifting assessments and empowering nurses., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Centella asiatica (Centella) is a traditional botanical medicine that shows promise in treating dementia based on behavioral alterations seen in animal models of aging and cognitive dysfunction. In order to determine if Centella could similarly improve cognitive function and reduce disease burden in multiple sclerosis (MS), we tested its effects in the neuroinflammatory experimental autoimmune encephalomyelitis (EAE) model of MS. In two independent experiments, C57BL/6J mice were treated following induction of EAE with either a standardized water extract of Centella (CAW) or placebo for 2 weeks. At the dosing schedule and concentrations tested, CAW did not improve behavioral performance, EAE motor disability, or degrees of demyelination. However, CAW-treated mice demonstrated increases in nuclear factor (erythroid-derived 2)-like 2 and other antioxidant response element genes, and increases in mitochondrial respiratory activity. Caw also decreased spinal cord inflammation. Our findings indicate that CAW can increase antioxidant gene expression and mitochondrial respiratory activity in mice with EAE, supporting investigation of the clinical effects of CAW in people with MS., Competing Interests: Competing Interests: The authors have no relevant financial or non-financial interests to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

There is considerable conceptual overlap between Level-2 Visual Perspective Taking (VPT-2) and Belief Reasoning; both cognitive processes require us to represent another's viewpoint and experience of reality while inhibiting our own egocentric representations. This study investigated if these facets of mentalising are distinct from one another in the general adult population. To do so, we developed a novel "Seeing-Believing Task" with which to compare VPT-2 and true belief (TB) reasoning directly - one in which both judgement types refer to the same state of reality, requiring identical responses, and where self and other perspectives can be dissociated. Across three preregistered online experiments, this task demonstrated consistent differences between these two cognitive processes; specifically, TB judgements were associated with slower response times than VPT-2. This suggests that VPT-2 and TB reasoning are at least partly distinct psychological processes. Further, the greater cognitive effort required for TB reasoning is unlikely to be explained by differences in mnemonic processing. We suggest, therefore, that VPT-2 and TB reasoning differ in the complexity of social processing involved and we discuss theoretical implications based on minimal vs. full-blown Theory of Mind. Future research must attempt to test these conjectures., (Copyright © 2023. Published by Elsevier B.V.)

Despite extensive coverage of a relationship between memory performance and executive function in the obsessive-compulsive disorder (OCD) literature, the relative contributions of specific aspects of executive control have remained elusive. We, therefore, extend our previous multilevel meta-analysis (Persson et al., 2021), where demand on executive function was the most significant determinant of memory deficits in OCD, and provide a finer-grained analysis of executive control via a segregation into top-down (attentional control, maintenance and updating, planning) and bottom-up (perceptual integration, perceptual salience) contributions. Our multilevel meta-analytic approach allowed us to accommodate the interdependency of 255 effect sizes from 131 studies, totaling 4,101 OCD patients. Results revealed that maintenance and updating (top-down) and perceptual integration (bottom-up) predicted memory performance generally, and specifically in those with clinical OCD. Exploratory analyses suggested that this effect may be somewhat different among subclinical OCD groups; however, these findings should be considered with conceptual and analytical caveats in mind. We explain these results via deficient sensory (perceptual integration) and working memory (maintenance and updating) gating mechanisms and propose a model to accommodate their expression in OC symptoms. In conclusion, our meta-analysis has expanded understanding of cognitive performance in OCD and identifies the possibility of untapped cognitive targets for intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

In 2016, New York City (NYC) began enforcing a sodium warning regulation at chain restaurants, requiring placement of an icon next to any menu item containing ≥2,300 mg sodium. As shifts in consumer purchases are a potential outcome of menu labeling, we investigated whether high-sodium purchases from NYC chains changed following policy implementation. Using receipts for verification, consumer purchases were assessed at 2 full-service (FSR) and 2 quick-service (QSR) chain restaurants in NYC and Yonkers, NY, which did not implement sodium menu labeling, in 2015 and 2017. Primary outcomes included the proportion of respondents purchasing high-sodium item(s) (containing ≥2,300 mg sodium) and mean sodium content of purchases; changes were assessed by difference-in-difference regression models, adjusted for demographic and location co-variates. At both FSR and QSR, there was not a significant change in the proportion of NYC respondents purchasing 1 or more high-sodium items, relative to Yonkers (FSR difference-in-difference: -4.6%, p = 0.364; QSR difference-in-difference: -8.9%, p = 0.196). Among NYC FSR respondents, mean sodium content of purchases significantly declined compared to Yonkers (difference-in-difference: -524 mg, p = 0.012); no changes in mean sodium were observed among QSR participants (difference-in-difference: 258 mg, p = 0.185). Although there was a reduction in mean sodium content of purchases among NYC FSR patrons following sodium warning icon implementation, the mechanism behind the relatively larger NYC decline is unknown., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Prasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases., Aim: To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle., Methods: Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male)., Results: In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to β-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration., Conclusions: Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes., (© 2023. The Author(s).)

This proof-of-concept study provides an appraisal of a remotely administered gamified Stop-Signal Task (gSST) for future use in studies using child sample. Performance on the standard Stop-Signal (SST) task has been shown previously to differentiate attention-deficit-hyperactivity-disorder groups from controls. As is the case with the SST, it was envisaged that those with greater impulsivity would perform worse than those with lower levels of impulsivity in the gSST. The potential advantage of the gSST is that it could be perceived as less monotonous than the original SST and has the potential to provide higher data quality in child samples, however future research will need to be conducted to determine this. The gSST was administered remotely via video chat to 30 child participants within a community sample aged 8-12 to investigate the effect of ADHD symptoms and intrinsic motivation on gSST performance. Qualitative data was collected based on feedback from participants to gain insight into how the gSST was received by participants. A positive correlation was observed between impulsive/hyperactivity and gSST performance, however there was insufficient evidence to suggest that impulsivity predicted performance. With regards to accuracy, results suggested that impulsivity level significantly predicted the rate of go-omission errors. No relationships were observed between intrinsic motivation inventory (IMI) subscales and performance or IMI and impulsivity. Nevertheless, mean IMI scores were overarchingly high for each of the IMI subscales, suggesting that regardless of performance and/or level of impulsive behaviour, the child sample obtained in this study demonstrated high levels of intrinsic motivation, which was supported by the predominantly positive subjective feedback provided by the child participants. The present study provides some evidence based on quantitative and qualitative results for the efficacy of gSST for use with children. Future research with a larger sample of children is warranted to examine how performance on the SST and gSST compare/differ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gallagher, Kessler, Bramham, Dechant and Friehs.)

Plasma apolipoprotein E levels were previously associated with the risk of developing Alzheimer's disease (AD), levels of cerebrospinal fluid AD biomarkers, cognition and imaging brain measures. Outside the brain, the liver is the primary source of apoE and liver transplantation studies have demonstrated that liver-derived apoE does not cross the blood-brain-barrier. How hepatic apoE may be implicated in behavioral and cognitive performance is not clear. In the current study, we behaviorally tested FRGN mice with humanized liver harboring the ε3/ε3 genotype (E3-human liver (HL)) and compared their behavioral and cognitive performance with that of age-matched ε3/ε3 targeted replacement (E3-TR) mice, the latter produces human apoE3 throughout the body whereas the E3-HL mice endogenously produce human apoE3 only in the liver. We also compared the liver weights and plasma apoE levels, and assessed whether plasma apoE levels were correlated with behavioral or cognitive measures in both models. E3-HL were more active but performed cognitively worse than E3-TR mice. E3-HL mice moved more in the open field containing objects, showed higher activity levels in the Y maze, showed higher activity levels during the baseline period in the fear conditioning test than E3-TR mice, and swam faster than E3-TR mice during training to locate the visible platform in the water maze. However, E3-HL mice showed reduced spatial memory retention in the water maze and reduced fear learning and contextual and cued fear memory than E3-TR mice. Liver weights were greater in E3-HL than E3-TR mice and sex-dependent only in the latter model. Plasma apoE3 levels were similar to those found in humans and comparable in female and male E3-TR mice but higher in female E3-HL mice. Finally, we found correlations between plasma apoE levels and behavioral and cognitive measures which were predominantly model-dependent. Our study demonstrates mouse-model dependent associations between plasma apoE levels, behavior and cognition in an 'AD-neutral' setting and suggests that a humanized liver might be sufficient to induce mouse behavioral and cognitive phenotypes., (© 2023. The Author(s).)

Studies have produced vastly disparate findings when exploring relationships between social networking site (SNS) usage and psychosocial well-being. These inconsistencies might reflect a lack of consideration for how people use SNS; specifically, while meaningful interactions are suggested to foster positive feelings, the passive consumption of others' feeds is proposed to have negative effects on users' well-being. To facilitate the empirical evaluation of these claims, the present study developed a computerised task to measure styles of usage on a mock SNS platform. Administering this Social Network Site Behaviour Task (SNSBT) online to 526 individuals, we identified three dissociable usage styles that extend the active-passive dichotomy employed frequently in the literature: passive use (consuming content posted by others), reactive use (reacting to others' content), and interactive use (interacting with others through content sharing). Furthermore, our data reveal that these usage styles differ on several measures of psychosocial variables employed frequently in the disparate literature: more interactive users reported greater feelings of social connectedness and social capital than passive or reactive users. Importantly, however, our results also reveal the multi-dimensional nature of usage styles, with online network size and time spent on SNS platforms serving as potentially confounding influences on some psychosocial measures. These findings not only advance our understanding of SNS behaviour by providing empirical support for theoretic propositions, but also demonstrate the utility of the SNSBT for experimental investigations into the psychosocial outcomes of different SNS usage styles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Shaw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Research into emotion regulation (ER) has focused primarily on the intra-personal process through which we regulate our own emotions intrinsically. More recently, however, studies have begun to explore the inter-personal nature of intrinsic ER - that is, how we regulate our emotions under the guidance of others. Preliminary evidence suggests that ER might be more effective when implemented in an inter- compared with an intra-personal manner, but these findings are based almost exclusively on self-reported ratings that capture only the subjective experience of emotions. The current study therefore investigated whether this apparent superiority of inter-personal intrinsic ER could be replicated and extended to physiological measures of affective reactions - namely, various metrics of electrodermal activity. In a within-subjects design, a sufficiently powered sample (N = 146) were required to down-regulate their emotional reactions to negatively valenced images using an ER strategy they had chosen themselves intra-personally or one that had been recommended to them inter-personally. Physiological responses converged to demonstrate the greater effectiveness of inter- over intra-personal ER in decreasing negative affective reactions, despite subjective ratings suggesting that participants perceived the opposite to be true. The superiority of inter- over intra-personal ER in physiological recordings was unrelated to individuals' perceptions of their ability to regulate their own emotions, however, and so it remains to be seen if and how such benefits extend to clinical populations., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Gluten degrading enzymes, which are commonly referred to as "glutenases," represent attractive candidates for the development of a pharmacological treatment of gluten related disorders, such as coeliac disease (CeD). Endoprotease-40 (E40), a novel glutenase secreted by the actinomycete Actinoallomurus A8 and recombinantly produced in S. lividans TK24, was shown to be active at pH 3 to 6 (optimum pH 5), resistant to pepsin and trypsin degradation, able to destroy immunotoxicity of both gliadin 33-mer peptide and whole proteins and to strongly reduce the response of specific T cells when added to gliadin in in vitro gastrointestinal digestion. This study aims to functionally assess the capabilities of Endoprotease-40 (E40) to detoxify residual gluten immunogenic peptides in gastrointestinal digesta of food matrices made of soft and durum wheat. The INFOGEST harmonized protocols were applied to the multicompartmental model of simulated human gastrointestinal digestion, for the quantitative assessment of residual gluten in liquid (beer) and solid (bread and pasta) foods, made of either soft or durum wheat. Proteomic and immunological techniques, and functional assays on intestinal T cell lines from celiac disease patients were used to identify gluten-derived immunogenic peptide sequences surviving in gastric and gastrointestinal digesta after the addition of E40 at increasing enzyme: wheat proteins ratios. During the gastric phase (2 h incubation time), the addition of E40 demonstrated an extensive (≥ 95%) dose-dependent detoxification of whole gluten in real food matrices. Overall, the residual gluten content was found at, or even below, the 20 ppm gluten-free threshold for soft and durum wheat-based food. Furthermore, unlike in untreated gastrointestinal digesta, none of the immunodominant α-gliadin peptides survived in E40-treated digesta. Traces of ω- and γ-gliadin derived immunogenic peptides were still detected in E40-treated digesta, but unable to stimulate celiac-intestinal T cells. In conclusion, E40 is a promising candidate for the oral enzymatic therapy of CeD, as a stand-alone enzyme being efficient along the complete gastrointestinal digestion of gluten., Competing Interests: MCC and KK were employed by Nemysis Limited. MCC was involved in the interpretation of data and drafting of the manuscript. CG and LC served as Scientific Advisor at Nemysis Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mamone, Comelli, Vitale, Di Stasio, Kessler, Mottola, Siano, Cavaletti and Gianfrani.)

Previous research has demonstrated that older adults make limited use of social cues as compared to younger adults. This has been investigated by testing the influence of gaze cues on attentional processes, with findings showing significantly smaller gaze-cuing effects for older than younger adults. Here, we aimed to investigate whether this would also result in age-related differences in the influence of gaze cues on working memory (WM). We therefore tested the effects of gaze cues from realistic human avatars on working memory across two experiments using dynamic head turns and more subtle eye gaze movements. We compared working memory for items looked at by the cue (congruent), looked away from by the cue (incongruent), and items shown when the cue looked down (neutral). Results demonstrated that for both older and younger adults, gaze cues influenced working memory processes, though there were some important differences related to the nature of the cue. When the cue made a dynamic head turn both younger and older adults showed an equivalent effect of gaze on attention. However, when only the eyes moved, while both the younger and older adults showed an effect of gaze on working memory, there appeared to be a difference in how the participants interpreted the neutral cue, with the older adults appearing to interpret the neutral cues in a similar way to the congruent cues. Overall, we provide important evidence that sharing attention benefits cognition across the life span. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Diffuse midline gliomas (DMGs) are highly aggressive, incurable childhood brain tumors. They present a clinical challenge due to many factors, including heterogeneity and diffuse infiltration, complicating disease management. Recent studies have described the existence of subclonal populations that may co-operate to drive pro-tumorigenic processes such as cellular invasion. However, a precise quantification of subclonal interactions is lacking, a problem that extends to other cancers. In this study, we combine spatial computational modeling of cellular interactions during invasion with co-evolution experiments of clonally disassembled patient-derived DMG cells. We design a Bayesian inference framework to quantify spatial subclonal interactions between molecular and phenotypically distinct lineages with different patterns of invasion. We show how this approach could discriminate genuine interactions, where one clone enhanced the invasive phenotype of another, from those apparently only due to the complex dynamics of spatially restricted growth. This study provides a framework for the quantification of subclonal interactions in DMG., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tight regulation of immediate early gene (IEG) expression is important for synaptic plasticity, learning, and memory. Recent work has suggested that DNA double strand breaks (DSBs) may have an adaptive role in post-mitotic cells to induce IEG expression. Physiological activity in cultured neurons as well as behavioral training leads to increased DSBs and subsequent IEG expression. Additionally, infusion of etoposide-a common cancer treatment that induces DSBs-impairs trace fear memory. Here, we assessed the effects of hippocampal infusion of 60 ng of etoposide on IEG expression, learning, and memory in 3-4 month-old C57Bl/6J mice. Etoposide altered expression of the immediate early genes cFos and Arc in the hippocampus and impaired hippocampus-dependent contextual fear memory. These data add to the growing evidence that DSBs play an important role in IEG expression, learning, and memory, opening avenues for developing novel treatment strategies for memory-related disorders., (© 2022. The Author(s).)

In this preregistered study (https://osf.io/s4rm9) we investigated the behavioural and neurological [electroencephalography; alpha (attention) and theta (effort)] effects of dynamic non-predictive social and non-social cues on working memory. In a virtual environment realistic human-avatars dynamically looked to the left or right side of a table. A moving stick served as a non-social control cue. Kitchen items were presented in the valid cued or invalid un-cued location for encoding. Behavioural findings showed a similar influence of the cues on working memory performance. Alpha power changes were equivalent for the cues during cueing and encoding, reflecting similar attentional processing. However, theta power changes revealed different patterns for the cues. Theta power increased more strongly for the non-social cue compared to the social cue during initial cueing. Furthermore, while for the non-social cue there was a significantly larger increase in theta power for valid compared to invalid conditions during encoding, this was reversed for the social cue, with a significantly larger increase in theta power for the invalid compared to valid conditions, indicating differences in the cues' effects on cognitive effort. Therefore, while social and non-social attention cues impact working memory performance in a similar fashion, the underlying neural mechanisms appear to differ., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate., Methods: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications., Results: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission., Conclusions: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

This data article describes electroencephalography (EEG) and behavioral data from 47 participants. Data was collected using a 64 channel eego™ sports mobile EEG system during a visual working memory task presented in virtual reality (VR) using Unity with an Oculus Rift S head-mounted display. In the memory task, participants had to remember the status of and details about objects presented on a table. Prior to object appearance a moving, 3D social avatar or non-social stick cue was presented which pointed to the left or right of the table. Items for encoding could appear in the valid, cued location or the invalid, un-cued location, with the cue being uninformative to the task. The cue type was presented within subjects, blocked, counterbalanced. The data (behavioral & EEG (raw and processed)), scripts and the full task are available. The data is set up to allow investigation of neural signals during attention cueing, and memory encoding, maintenance and retrieval. The main novelty of the dataset is the presentation of the social avatar and non-social stick cue in VR within subjects, thus, allowing comparison across time points, including a period of eye contact. The data is also of interest to researchers interested in the neural corelates of working memory. Further, it is of interest to researchers interested in combining VR and EEG., 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., (© 2022 The Author(s). Published by Elsevier Inc.)

Age-related decline in theory of mind (ToM) may be due to waning executive control, which is necessary for resolving conflict when reasoning about other individuals' mental states. We assessed how older ( n = 50) and younger ( n = 50) adults were affected by three theoretically relevant sources of conflict within ToM: competing self-other perspectives, competing cued locations, and outcome knowledge. We examined which best accounted for age-related difficulty with ToM. Our data show unexpected similarity between age groups when people are representing a belief incongruent with their own. Individual differences in attention and response speed best explained the degree of conflict experienced through incompatible self-other perspectives. However, older adults were disproportionately affected by managing conflict between cued locations. Age and spatial working memory were most relevant for predicting the magnitude of conflict elicited by conflicting cued locations. We suggest that previous studies may have underestimated older adults' ToM proficiency by including unnecessary conflict in ToM tasks.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has left many unanswered questions for patients with neurological disorders and the providers caring for them. Elderly and immunocompromised patients are at increased risk for severe symptoms due to COVID-19, and the virus may increase symptoms of underlying neurological illness, particularly for those with significant bulbar and respiratory weakness or other neurologic disability. Emerging SARS-CoV-2 vaccines offer substantial protection from symptomatic infection, but both patients and providers may have concerns regarding theoretical risks of vaccination, including vaccine safety and efficacy in the context of immunotherapy and the potential for precipitating or exacerbating neurological symptoms. In this statement on behalf of the Quality Committee of the AAN we review the current literature, focusing on COVID-19 infection in adults with neurological disease, in order to elucidate risks and benefits of vaccination in these individuals. Based on existing evidence, neurologists should recommend COVID-19 vaccination to their patients. For those patients being treated with immunotherapies, attention should be paid to timing of vaccination with respect to treatment and the potential for an attenuated immune response., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

Background: Recent behavioural research has reported age-related changes in the costs of refocusing attention from a temporal (rapid serial visual presentation) to a spatial (visual search) task. Using magnetoencephalography, we have now compared the neural signatures of attention refocusing between three age groups (19-30, 40-49 and 60+ years) and found differences in task-related modulation and cortical localisation of alpha and theta oscillations. Efficient, faster refocusing in the youngest group compared to both middle age and older groups was reflected in parietal theta effects that were significantly reduced in the older groups. Residual parietal theta activity in older individuals was beneficial to attentional refocusing and could reflect preserved attention mechanisms. Slowed refocusing of attention, especially when a target required consolidation, in the older and middle-aged adults was accompanied by a posterior theta deficit and increased recruitment of frontal (middle-aged and older groups) and temporal (older group only) areas, demonstrating a posterior to anterior processing shift. Theta but not alpha modulation correlated with task performance, suggesting that older adults' stronger and more widely distributed alpha power modulation could reflect decreased neural precision or dedifferentiation but requires further investigation. Our results demonstrate that older adults present with different alpha and theta oscillatory signatures during attentional control, reflecting cognitive decline and, potentially, also different cognitive strategies in an attempt to compensate for decline., (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Even though memory performance is a commonly researched aspect of obsessive-compulsive disorder (OCD), a coherent and unified explanation of the role of specific cognitive factors has remained elusive. To address this, the present meta-analysis examined the predictive validity of Harkin and Kessler's (2011b) executive function, binding complexity, and memory load (EBL) Classification System concerning affected versus unaffected memory performance in OCD. We employed a multilevel meta-analytic approach (Viechtbauer, 2010) to accommodate the interdependent nature of the EBL model and interdependency of effect sizes (305 effect sizes from 144 studies, including 4,424 OCD patients). Results revealed that the EBL model predicted memory performance; that is, as EBL demand increases, those with OCD performed progressively worse on memory tasks. Executive function was the driving mechanism behind the EBL's impact on OCD memory performance, as it negated binding complexity, memory load, and visual or verbal task differences. Comparisons of subtask effect sizes were also generally in accord with the cognitive parameters of the EBL taxonomy. We conclude that standardized coding of tasks along individual cognitive dimensions and multilevel meta-analyses provides a new approach to examine multidimensional models of memory and cognitive performance in OCD and other disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD., Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients. Functional effects of pathogenic variants identified were validated in cell, tissue, and mouse models., Results: We identified five functional variants in THSD4 of which two heterozygous variants lead to a premature termination codon. THSD4 encodes ADAMTSL6 (member of the ADAMTS/L superfamily), a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4 +/- mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4 +/- mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix., Conclusion: These findings highlight the role of ADAMTSL6 in aortic physiology and TAAD pathogenesis. They will improve TAAD management and help develop new targeted therapies.

Prior research with a sample of male probationers indicates severity levels of one arresting intimate partner violence (IPV) offense are predictive of future frequency of such offenses and treatment completion. This study is an extended analysis looking at severity ratings across two IPV offenses to measure violence stability. The stability of IPV severity levels was analyzed in a sample of offenders in Lake County, Illinois. Offender subtypes of generally violent (GV) men and family only (FO) violent men were incorporated into stability analyses using generalized linear mixed modeling (GLMM) to determine whether certain types of offenders vary in violence levels over time. The purpose was to determine the predictive utility of using a single offense to determine the domestic violence trajectory for male probationers. Reoffense records of 80 men were collected from a larger sample of 352 males, ages 17 to 72 placed on probation in Lake County, Illinois, between 2006 and 2008. Severity of offenses was coded dichotomously based on a behaviorally derived measure. Results demonstrate 64% of reoffenders remained stable in IPV severity. Overall, severity levels decreased across time. This is the first study to use a probationary sample of men to analyze violence stability trends over time. This study confirms the utility of measuring a single offense to predict future violence trajectories for IPV offenders.

We recently reported that refocusing attention between temporal and spatial tasks becomes more difficult with increasing age, which could impair daily activities such as driving (Callaghan et al., 2017). Here, we investigated the extent to which difficulties in refocusing attention extend to naturalistic settings such as simulated driving. A total of 118 participants in five age groups (18-30; 40-49; 50-59; 60-69; 70-91 years) were compared during continuous simulated driving, where they repeatedly switched from braking due to traffic ahead (a spatially focal yet temporally complex task) to reading a motorway road sign (a spatially more distributed task). Sequential-Task (switching) performance was compared to Single-Task performance (road sign only) to calculate age-related switch-costs. Electroencephalography was recorded in 34 participants (17 in the 18-30 and 17 in the 60+ years groups) to explore age-related changes in the neural oscillatory signatures of refocusing attention while driving. We indeed observed age-related impairments in attentional refocusing, evidenced by increased switch-costs in response times and by deficient modulation of theta and alpha frequencies. Our findings highlight virtual reality (VR) and Neuro-VR as important methodologies for future psychological and gerontological research.

Context: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied., Objective: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control., Design: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order., Results: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion., Conclusions: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The pain associated with pricking the fingertip for blood glucose self-testing is considered to be a major burden in diabetes treatment. This study was performed to evaluate the system accuracy of the invasive TensorTip Combo Glucometer (CoG) device component in accordance with ISO15197:2015 requirements and to explore the accuracy of the noninvasive tissue glucose prediction component., Methods: One hundred samples were obtained from people with type 1 and type 2 diabetes and healthy volunteers (43 females, 57 males; age: 53 ± 16 years), with glucose distribution as requested by the ISO standard. Three strip lots were tested twice by healthcare professionals in comparison to YSI 2300 Stat Plus reference method followed by a noninvasive tissue glucose reading (NI-CoG). Mean Absolute (Relative) Difference (MARD) was calculated and a consensus error grid (CEG) analysis was performed., Results: The ISO system accuracy criteria were met with the invasive strip technology by 586/600 of the data points (97.1%) and for each strip lot separately. All invasive results (100%) were within CEG-zone A and total MARD was calculated to be 7.1%. With the noninvasive reading, 99% of raw data points were in A + B (91.1% and 7.8%), and the total MARD was calculated to be 18.1%., Discussion: The invasive component of the CoG device was shown to be in full compliance with the current ISO15197 criteria. Good results were also obtained with the NI-CoG tissue glucose prediction. This noninvasive technology would potentially be suitable for frequent pain-free glucose monitoring in many people with diabetes.

A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning. SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner., (Copyright © 2020 the authors.)