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Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset 1 . Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals 2-4 , but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time., (© 2024. The Author(s).)

Motor-task functional magnetic resonance imaging (fMRI) is crucial in the study of several clinical conditions, including stroke and Parkinson's disease. However, motor-task fMRI is complicated by task-correlated head motion, which can be magnified in clinical populations and confounds motor activation results. One method that may mitigate this issue is multi-echo independent component analysis (ME-ICA), which has been shown to separate the effects of head motion from the desired blood oxygenation level dependent (BOLD) signal but has not been tested in motor-task datasets with high amounts of motion. In this study, we collected an fMRI dataset from a healthy population who performed a hand grasp task with and without task-correlated amplified head motion to simulate a motor-impaired population. We analyzed these data using three models: single-echo (SE), multi-echo optimally combined (ME-OC), and ME-ICA. We compared the models' performance in mitigating the effects of head motion on the subject level and group level. On the subject level, ME-ICA better dissociated the effects of head motion from the BOLD signal and reduced noise. Both ME models led to increased t-statistics in brain motor regions. In scans with high levels of motion, ME-ICA additionally mitigated artifacts and increased stability of beta coefficient estimates, compared to SE. On the group level, all three models produced activation clusters in expected motor areas in scans with both low and high motion, indicating that group-level averaging may also sufficiently resolve motion artifacts that vary by subject. These findings demonstrate that ME-ICA is a useful tool for subject-level analysis of motor-task data with high levels of task-correlated head motion. The improvements afforded by ME-ICA are critical to improve reliability of subject-level activation maps for clinical populations in which group-level analysis may not be feasible or appropriate, for example, in a chronic stroke cohort with varying stroke location and degree of tissue damage., Competing Interests: DECLARATION OF COMPETING INTEREST The authors declare no competing financial interests.

Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO 2 (P ET CO 2 ) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable P ET CO 2 recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM-BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with P ET CO 2 . We define a threshold to determine whether a P ET CO 2 recording has "sufficient" quality for CVR mapping and perform these comparisons in 16 datasets with sufficient P ET CO 2 and 6 datasets with insufficient P ET CO 2 . When P ET CO 2 quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from P ET CO 2 (after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to P ET CO 2 with an RVT regressor but may be underestimated with the average GM-BOLD regressor. Importantly, when P ET CO 2 quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient P ET CO 2 recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier Inc.)

Cerebrovascular reactivity (CVR), an important indicator of cerebrovascular health, is commonly studied with the Blood Oxygenation Level Dependent functional MRI (BOLD-fMRI) response to a vasoactive stimulus. Theoretical and empirical evidence suggests that baseline cerebral blood flow (CBF) modulates BOLD signal amplitude and may influence BOLD-CVR estimates. We address how acquisition and modeling choices affect the relationship between baseline cerebral blood flow (bCBF) and BOLD-CVR: whether BOLD-CVR is modeled with the inclusion of a breathing task, and whether BOLD-CVR amplitudes are optimized for hemodynamic lag effects. We assessed between-subject correlations of average GM values and within-subject spatial correlations across cortical regions. Our results suggest that a breathing task addition to a resting-state acquisition, alongside lag-optimization within BOLD-CVR modeling, can improve BOLD-CVR correlations with bCBF, both between- and within-subjects, likely because these CVR estimates are more physiologically accurate. We report positive correlations between bCBF and BOLD-CVR, both between- and within-subjects. The physiological explanation of this positive correlation is unclear; research with larger samples and tightly controlled vasoactive stimuli is needed. Insights into what drives variability in BOLD-CVR measurements and related measurements of cerebrovascular function are particularly relevant when interpreting results in populations with altered vascular and/or metabolic baselines or impaired cerebrovascular reserve., 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 © 2022 Stickland, Zvolanek, Moia, Caballero-Gaudes and Bright.)

Analyses of brain function and anatomy using shared neuroimaging data is an important development, and have acquired the potential to be scaled up with the specification of a new Brain Imaging Data Structure (BIDS) standard. To date, a variety of software tools help researchers in converting their source data to BIDS but often require programming skills or are tailored to specific institutes, data sets, or data formats. In this paper, we introduce BIDScoin, a cross-platform, flexible, and user-friendly converter that provides a graphical user interface (GUI) to help users finding their way in BIDS standard. BIDScoin does not require programming skills to be set up and used and supports plugins to extend their functionality. In this paper, we show its design and demonstrate how it can be applied to a downloadable tutorial data set. BIDScoin is distributed as free and open-source software to foster the community-driven effort to promote and facilitate the use of BIDS standard., 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 © 2022 Zwiers, Moia and Oostenveld.)

Cerebrovascular reactivity (CVR), defined here as the Blood Oxygenation Level Dependent (BOLD) response to a CO 2 pressure change, is a useful metric of cerebrovascular function. Both the amplitude and the timing (hemodynamic lag) of the CVR response can bring insight into the nature of a cerebrovascular pathology and aid in understanding noise confounds when using functional Magnetic Resonance Imaging (fMRI) to study neural activity. This research assessed a practical modification to a typical resting-state fMRI protocol, to improve the characterization of cerebrovascular function. In 9 healthy subjects, we modelled CVR and lag in three resting-state data segments, and in data segments which added a 2-3 minute breathing task to the start of a resting-state segment. Two different breathing tasks were used to induce fluctuations in arterial CO 2 pressure: a breath-hold task to induce hypercapnia (CO 2 increase) and a cued deep breathing task to induce hypocapnia (CO 2 decrease). Our analysis produced voxel-wise estimates of the amplitude (CVR) and timing (lag) of the BOLD-fMRI response to CO 2 by systematically shifting the CO 2 regressor in time to optimize the model fit. This optimization inherently increases gray matter CVR values and fit statistics. The inclusion of a simple breathing task, compared to a resting-state scan only, increases the number of voxels in the brain that have a significant relationship between CO 2 and BOLD-fMRI signals, and improves our confidence in the plausibility of voxel-wise CVR and hemodynamic lag estimates. We demonstrate the clinical utility and feasibility of this protocol in an incidental finding of Moyamoya disease, and explore the possibilities and challenges of using this protocol in younger populations. This hybrid protocol has direct applications for CVR mapping in both research and clinical settings and wider applications for fMRI denoising and interpretation., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress., Competing Interests: Declaration of interests Anisha Keshavan is an employee of Octave Bioscience., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Performing a BOLD functional MRI (fMRI) acquisition during breath-hold (BH) tasks is a non-invasive, robust method to estimate cerebrovascular reactivity (CVR). However, movement and breathing-related artefacts caused by the BH can substantially hinder CVR estimates due to their high temporal collinearity with the effect of interest, and attention has to be paid when choosing which analysis model should be applied to the data. In this study, we evaluate the performance of multiple analysis strategies based on lagged general linear models applied on multi-echo BOLD fMRI data, acquired in ten subjects performing a BH task during ten sessions, to obtain subject-specific CVR and haemodynamic lag estimates. The evaluated approaches range from conventional regression models, i.e. including drifts and motion timecourses as nuisance regressors, applied on single-echo or optimally-combined data, to more complex models including regressors obtained from multi-echo independent component analysis with different grades of orthogonalization in order to preserve the effect of interest, i.e. the CVR. We compare these models in terms of their ability to make signal intensity changes independent from motion, as well as the reliability as measured by voxelwise intraclass correlation coefficients of both CVR and lag maps over time. Our results reveal that a conservative independent component analysis model applied on the optimally-combined multi-echo fMRI signal offers the largest reduction of motion-related effects in the signal, while yielding reliable CVR amplitude and lag estimates, although a conventional regression model applied on the optimally-combined data results in similar estimates. This work demonstrates the usefulness of multi-echo based fMRI acquisitions and independent component analysis denoising for precision mapping of CVR in single subjects based on BH paradigms, fostering its potential as a clinically-viable neuroimaging tool for individual patients. It also proves that the way in which data-driven regressors should be incorporated in the analysis model is not straight-forward due to their complex interaction with the BH-induced BOLD response., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cerebrovascular Reactivity (CVR), the responsiveness of blood vessels to a vasodilatory stimulus, is an important indicator of cerebrovascular health. Assessing CVR with fMRI, we can measure the change in the Blood Oxygen Level Dependent (BOLD) response induced by a change in CO2 pressure (%BOLD/mmHg). However, there exists a temporal offset between the recorded CO2 pressure and the local BOLD response, due to both measurement and physiological delays. If this offset is not corrected for, voxel-wise CVR values will not be accurate. In this paper, we propose a framework for mapping hemodynamic lag in breath-hold fMRI data. As breath-hold tasks drive task-correlated head motion artifacts in BOLD fMRI data, our framework for lag estimation fits a model that includes polynomial terms and head motion parameters, as well as a shifted variant of the CO2 regressor (±9 s in 0.3 s increments), and the hemodynamic lag at each voxel is the shift producing the maximum total model R2 within physiological constraints. This approach is evaluated in 8 subjects with multi-echo fMRI data, resulting in robust maps of hemodynamic delay that show consistent regional variation across subjects, and improved contrast-to-noise compared to methods where motion regression is ignored or performed earlier in preprocessing.Clinical Relevance- We map hemodynamic lag using breathhold fMRI, providing insight into vascular transit times and improving the regional accuracy of cerebrovascular reactivity measurements.

This work introduces a novel algorithm for deconvolution of the BOLD signal in multi-echo fMRI data: Multi-echo Sparse Paradigm Free Mapping (ME-SPFM). Assuming a linear dependence of the BOLD percent signal change on the echo time (TE) and using sparsity-promoting regularized least squares estimation, ME-SPFM yields voxelwise time-varying estimates of the changes in the apparent transverse relaxation (ΔR 2 ⁎ ) without prior knowledge of the timings of individual BOLD events. Our results in multi-echo fMRI data collected during a multi-task event-related paradigm at 3 Tesla demonstrate that the maps of R 2 ⁎ changes obtained with ME-SPFM at the times of the stimulus trials show high spatial and temporal concordance with the activation maps and BOLD signals obtained with standard model-based analysis. This method yields estimates of ΔR 2 ⁎ having physiologically plausible values. Owing to its ability to blindly detect events, ME-SPFM also enables us to map ΔR 2 ⁎ associated with spontaneous, transient BOLD responses occurring between trials. This framework is a step towards deciphering the dynamic nature of brain activity in naturalistic paradigms, resting-state or experimental paradigms with unknown timing of the BOLD events., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Impairment in orexigenic/anorexigenic hormone balance may be key in the pathogenesis of protein energy wasting in children with chronic kidney disease (CKD). Measurement of ghrelin and obestatin concentrations in children with CKD would help assess the potential contribution of these hormones to uremic protein energy wasting., Methods: This was a cross-sectional case-control study. Acylated and unacylated ghrelin and obestatin were measured in 42 children on conservative treatment (CT), 20 children on hemodialysis, 48 pediatric renal transplant (RTx) recipients and 43 controls (CTR) (mean age 11.9, range 5-20 years). Weight, height and bicipital, tricipital, subscapular and suprailiac folds were measured, and the body mass index-standard deviation score (BMI-SDS), percentage of fat mass and fat-free mass were calculated. Urea and creatinine were measured and the glomerular filtration rate (GFR) calculated., Results: Unacylated ghrelin level was higher in patients than controls (p = 0.0001), with the highest levels found in hemodialysis patients (p = 0.001 vs. CKD-CT, p = 0.0001 vs. RTx, p < 0.0001 vs. CTR). Obestatin level was significantly higher in patients on hemodialysis than those on conservative treatment, RTx recipients and controls (p < 0.0001 in each case). Unacylated ghrelin negatively correlated with weight-SDS (p < 0.0001), BMI-SDS (p = 0.0005) and percentage fat mass (p = 0.004) and positively correlated with percentage fat-free mass (p = 0.004). Obestatin concentration negatively correlated with weight-SDS (p = 0.007). Unacylated ghrelin and obestatin concentrations positively correlated with creatinine and urea and inversely with eGFR, even after adjustments for gender, age, puberty and BMI-SDS (p < 0.0001 for each model)., Conclusions: Unacylated ghrelin and obestatin, negatively related to renal function, seem to be promising inverse indicators of nutritional status in children with CKD. Potential therapeutic implications in terms of optimization of their removal in patients on hemodialysis could be hypothesized.

Background: Mutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder characterized by severe growth retardation. Biochemically, patients present normal to high circulating GH levels, in presence of very low or undetectable IGF-I levels, which do not rise after rhGH treatment., Case Presentation: We describe the case of a 3.8 years old girl with symmetrical short stature (-3.76 SDS), low IGF-1 and IGFBP-3, in presence of normal GH levels. Parents were not relatives and there was no family history of short stature. During the second day of birth, she developed severe hypoglycaemia that required glucose infusion. She presented frontal bossing and depressed nasal bridge. IGF-1 generation test showed no response, suggesting a GH resistance evidence. In the hypothesis of Laron Syndrome, we decided to perform a molecular analysis of Growth Hormone Receptor (GHR) gene. This analysis demonstrated that the patient was compound heterozygote for two missense mutations., Conclusions: GHR gene mutations are a well demonstrated cause of GH insensitivity. In heterozygous patients, probably the normal stature may be achieved by a compensatory mechanism of GH secretion or signalling. On the contrary, in homozygous or compound heterozygous patients these compensatory mechanisms are inadequate, and short stature may be the consequence.

Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies. In 20 anesthetized pigs, intracoronary 100 pmol/mL DAG infusion with a constant heart rate and aortic blood pressure, increased coronary blood flow and NO release, whereas reducing coronary vascular resistances (P < .05). Dose responses to DAG were evaluated in five pigs. No effects on cardiac contractility/relaxation or myocardial oxygen consumption were observed. Moreover, whereas the blockade of muscarinic cholinoceptors (n = 5) or α- and β-adrenoceptors (n = 5 each) did not abolish the observed responses, NO synthase inhibition (n = 5) prevented the effects of DAG on coronary blood flow and NO release. In coronary artery endothelial cells, DAG dose dependently increased NO release through cAMP signaling and ERK1/2, Akt, and p38 MAPK involvement as well as the phosphorylation of endothelial NO synthase. In conclusion, in anesthetized pigs, DAG primarily increased cardiac perfusion through the involvement of NO release. Moreover, the phosphorylation of ERK1/2 and Akt appears to play roles in eliciting the observed NO production in coronary artery endothelial cells.

Background: Nutrition and growth in early postnatal life have a role in future diseases. Our aim was to investigate adiponectin oligomers in adequate-for-gestational-age obese children with respect to type and duration of feeding in the first year of life., Methods: Adiponectin oligomers and cardiometabolic risk factors were measured in 113 adequate-for-gestational-age obese children, divided into group A (prolonged breast feeding, >6 mo), group B (short breast feeding, 1-6 mo), and group C (formula feeding from birth)., Results: All the parameters were similar among the groups. Adiponectin oligomers did not correlate with gestational age, months of breast feeding, and time of weaning. Total and high-molecular weight adiponectin were differently distributed across gender and pubertal stages (P < 0.02), being lower in males from the start of puberty. Prepregnancy BMI and at the end of the pregnancy were negatively associated (P < 0.04) with total and medium-molecular weight adiponectin in female and male offspring, respectively., Conclusions: Adiponectin oligomers and metabolic characteristics are similarly distributed in adequate-for-gestational-age obese children, irrespective of the type and duration of the feeding in the first year of life. Gender and mother's BMI in pregnancy are contributors to adiponectin regulation. Further studies will explain whether breastfeeding protects against metabolic impairment later in life.

Purpose: In vitro or in animal models of epilepsy, ghrelin showed a clear anticonvulsant action, whose mechanisms are somewhat obscure. In humans however, a controversial relation exists between ghrelin and epilepsy. Yet most studies investigated just total ghrelin levels, without a proper distinction between acylated (AG) or unacylated ghrelin (UAG). We thus evaluated separately AG and UAG interictal levels in adult patients with epilepsy, and their relation to clinical features., Method: Cross-sectional study in a tertiary referral centre. Fifty-six patients were recruited: 19 with idiopathic generalized epilepsy, 18 with cryptogenic focal epilepsy and 19 with symptomatic focal epilepsy. Twenty-six healthy subjects of similar age, sex and body mass index (BMI) acted as controls. AG and UAG levels were measured following an overnight fasting and contrasted to the clinical and biometric features., Results: AG and UAG levels were similar between patients and controls. The AG/UAG ratio was higher in patients, also when weighted for covariates (age, BMI, gender, and drugs). Splitting patients according to their epileptic syndrome, drug-resistance or antiepileptic drug number/type resulted in no significant difference in AG, UAG or their ratio. Yet, AG and UAG levels were positively predicted by disease duration, independently by confounders., Conclusion: In adult patients with epilepsy, interictal ghrelin levels did not differ from controls, though the AG/UAG ratio was imbalanced. Interpretation of the latter phenomenon is uncertain. Further, levels of AG and UAG were in direct proportion to disease duration, which may represent a long-term compensatory mechanism, antagonistic to the epileptic process., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Neuroscience studies entail the generation of massive collections of heterogeneous data (e.g. demographics, clinical records, medical images). Integration and analysis of such data in research centers is pivotal for elucidating disease mechanisms and improving clinical outcomes. However, data collection in clinics often relies on non-standardized methods, such as paper-based documentation. Moreover, diverse data types are collected in different departments hindering efficient data organization, secure sharing and compliance to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. Henceforth, in this manuscript we present a specialized data management system designed to enhance research workflows in Deep Brain Stimulation (DBS), a state-of-the-art neurosurgical procedure employed to treat symptoms of movement and psychiatric disorders. The system leverages REDCap to promote accurate data capture in hospital settings and secure sharing with research institutes, Brain Imaging Data Structure (BIDS) as image storing standard and a DBS-specific SQLite database as comprehensive data store and unified interface to all data types. A self-developed Python tool automates the data flow between these three components, ensuring their full interoperability. The proposed framework has already been successfully employed for capturing and analyzing data of 107 patients from 2 medical institutions. It effectively addresses the challenges of managing, sharing and retrieving diverse data types, fostering advancements in data quality, organization, analysis, and collaboration among medical and research institutions. [ABSTRACT FROM AUTHOR]

Halide perovskites are a class of materials of consolidated optoelectronic and electrochemical applications, reaching efficiencies compared to established materials in respective fields. In this scenario, the design and understanding of composition–structure–property relations is imperative. In solid solutions containing mixed cations, some direct relations between the sizes of the substituents and the properties of perovskites are generally observed. However, in several cases, these relations are not observed, implying that other characteristics of these cations play a major role. Despite its importance, this understanding has not been comprehensively deepened. To address this issue, we synthesized and characterized the structure, electrical behavior, and stability of methylammonium lead iodide-based perovskites with equal amounts of the substituents guanidinium, ethylammonium, and acetamidinium. These three large organic cations have essentially equal sizes but other remarkably different characteristics, such as the number of N–H bonds, intrinsic dipole moment, and order of C–N bonds. Herein, we show that these cations have dramatically different effects over important fundamental and applied properties of resulting perovskites, including the orthorhombic-to-tetragonal and tetragonal-to-cubic phase transitions, microstructural development, ionic conductivity, I–V hysteresis, electronic carrier mobility, and stability against light-induced degradation. These effects are correlated with the characteristics of the large substituent cations and help pave the way for a better rational chemical design of halide perovskites. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs). Methods: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow–Pittsburgh cerebral performance category (CPC) scale at 3 months after CA. Results: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001). Conclusions: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses. Trial registration: NCT05966389 (Registered July 27, 2023). [ABSTRACT FROM AUTHOR]

Context and Objective: Ghrelin secretion is altered at the onset and after the start of insulin therapy in children with type 1 diabetes. Contemporary regulation of acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (OBST) remains undefined in this disease. It is unknown as to whether they could be good predictors of changes in glucose and metabolic control., Design, Setting, and Subjects: This was a longitudinal study conducted in a tertiary care center. AG, UAG, and OBST were measured at baseline and after 2 years of follow-up in 51 children and adolescents with a history of type 1 diabetes extending beyond 1 year. A total of 33 healthy matched subjects were used as controls., Results: Age-, puberty-, and body mass index-adjusted UAG levels were lower (P < .005) and OBST levels were higher (P < .009) in children with type 1 diabetes, with respect to controls. AG levels were similar to controls, but all ratios of the three peptides are altered in diabetic patients. OBST (P < .05) was negatively correlated with C-peptide (P < .05) and insulin antibodies (P < .008) at the onset of diabetes. In diabetic patients, baseline AG and UAG levels were negatively correlated with insulin dosage in the short and long term (P < .001). AG, but not OBST, was positively correlated with C-peptide levels 2 years after diagnosis (P < .05). Overall, the peptides were not predictive of glucose and metabolic control., Conclusions: UAG, AG, OBST, and their ratios are differently regulated in children with type 1 diabetes, suggesting a role in the metabolic balance of the disease, with insulin a likely regulator of AG and UAG. The peptides do not appear to be good long-term predictors of glucose control, with further investigations needed to explain whether OBST could be a precocious predictor of islet dysfunction.

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml). Plasma proteomic analyses by two dimensional (2D)-electrophoresis were performed at baseline in all subjects. VDD subjects underwent a 12mo treatment with 3000 IU vitamin D3 once a week to confirm the proteomic analyses. The proteomic analyses identified 53 "spots" that differed between VDD and NVD (p<0.05), amongst which adiponectin was identified. Adiponectin was selected for confirmational studies due to its tight association with obesity and diabetes mellitus. Western Immunoblot (WIB) analyses of 2D-gels demonstrated a downregulation of adiponectin in VDD subjects, which was confirmed in the plasma from VDD with respect to NVD subjects (p<0.035) and increased following 12mo vitamin D3 supplementation in VDD subjects (p<0.02). High molecular weight (HMW) adiponectin, a surrogate indicator of insulin sensitivity, was significantly lower in VDD subjects (p<0.02) and improved with vitamin D3 supplementation (p<0.042). A direct effect in vitro of 1α,25-(OH)2D3 on adipocyte adiponectin synthesis was demonstrated, with adiponectin and its multimeric forms upregulated, even at low pharmacological doses (10(-9) M) of 1α,25-(OH)2D3. This upregulation was paralleled by the adiponectin interactive protein, DsbA-L, suggesting that the VD regulation of adiponectin involves post-transciptional events. Using a proteomic approach, multimeric adiponectin has been identified as a key plasma protein that links VDD to pediatric obesity.

Idiopathic Short Stature (ISS) defines a condition in which height is <-2SD compared to the mean of a reference population where systemic, endocrinological, nutritional or chromosomal disorders have not been identified and diagnosis is based on exclusion of any known causes of short stature. JAK/STAT pathway is triggered by GH binding to the GH receptor and promotes cellular growth through transcription of GH-responsive genes. In order to identify "candidate genes" differently expressed in ISS subjects with respect to control ones, we analyzed the expression of 84 genes related to JAK/STAT pathway by RT(2) Profiler PCR array approach in a total of 10 subjects. Then, we validated the observed data by Real Time PCR and ELISA assays in a major number of subjects. We found two genes that were differently expressed in ISS subjects with respect to the control group: CXCL9 and FCGR1A/CD64, both significantly up-regulated (fold change 2.17 and 1.70, respectively) and belonging to family of IFN-γ-inducible factors. Further, ISS subjects showed an increased gene expression of IFN-γ and IFI16, higher serum levels of IFN-γ but similar levels of CXCL9 when compared to healthy subjects. In addition, we showed a pubertal modulation of CXCL9 levels. These data suggest that inflammatory and regulatory factors of the cell cycle may be involved in the ISS condition, introducing a new perspective to its etiology.

Objective: Subclinical hypothyroidism (SH) is quite common in children and adolescents. The natural history of this condition and the potential effects of replacement therapy need to be known to properly manage SH. The aim of this review is to analyze: i) the spontaneous evolution of SH, in terms of the rate of reversion to euthyroidism, the persistence of SH, or the progression to over hypothyroidism; and ii) the effects of replacement therapy, with respect to auxological data, thyroid volume, and neuropsychological functions., Methods: We systematically searched PubMed, Cochrane, and EMBASE (1990-2012) and identified 39 potentially relevant articles of which only 15 articles were suitable to be included., Results and Conclusions: SH in children is a remitting process with a low risk of evolution toward overt hypothyroidism. Most of the subjects reverted to euthyroidism or remained SH, with a rate of evolution toward overt hypothyroidism ranging between 0 and 28.8%, being 50% in only one study (nine articles). The initial presence of goiter and elevated thyroglobulin antibodies, the presence of celiac disease, and a progressive increase in thyroperoxidase antibodies and TSH value predict a progression toward overt hypothyroidism. Replacement therapy is not justified in children with SH but with TSH 5-10 mIU/l, no goiter, and negative antithyroid antibodies. An increased growth velocity was observed in children treated with levothyroxine (l-T(4); two articles). l-T(4) reduced thyroid volume in 25-100% of children with SH and autoimmune thyroiditis (two studies). No effects on neuropsychological functions (one study) and posttreatment evolution of SH (one study) were reported.

Isolated GH deficiency (IGHD) is a rare disorder that occurs as an idiopathic form in most cases. The pathway JAK/STAT promotes cellular growth and it could be implicated in this condition. In order to characterize IGHD in the pediatric population and identify genes differently expressed before and after GH therapy, we performed a quantitative evaluation of 84 genes related to the JAK/STAT pathway which, by promoting cellular growth. RT(2) Profiler PCR Array and the other/subsequent evaluations were performed in three children with severe IGHD before and after 6 months of GH therapy and in three matched normal children. Gene profiling was modified by the IGHD status and the GH therapy, with a modulation of GHR and some inflammatory genes such as CRP. We found a heterozygous nonsense mutation R43X in the GHR gene in two out of three IGHD subjects, despite a good response to therapy. After therapy cardiovascular markers linked to genes as IL6, IL8 and TNF-α displayed a trend toward reduction. Pre- and post therapy status differently affects gene expression. Mutational screening of GHR may be useful in investigating IGHD's etiology. Genes linked to inflammation suggest to evaluate cardiovascular risks also in pediatric IGHD subjects.

Objective: Mutations in HESX1 represent a rare cause of GH deficiency (GHD) associated with a broad spectrum of other anomalies. We searched for causative mutations in a cohort of 244 Italian patients affected by combined and isolated GHD (IGHD)., Methods: The HESX1 gene-coding region and exon-intron boundaries were screened by denaturing HPLC scanning., Results: A novel mutation adjacent to the invariant donor splice site of intron 2 (c.357+3G>A) was identified at the heterozygous state in an IGHD patient. The in vitro and in vivo mRNA analysis of the wild-type HESX1 allele revealed the presence of the whole cDNA and two isoforms lacking exon 2 and exons 2-3 respectively. The mutant HESX1 allele yielded only two splicing products, the whole cDNA and the cDNA missing exons 2-3, whereas the mRNA lacking exon 2 was absent. An in vitro assay demonstrated that the exon 2-deleted mRNA, predicting a prematurely truncated protein, is subjected to nonsense-mediated mRNA decay (NMD)., Conclusions: The c.357+3G>A mutation prevents the generation of one of the alternative isoforms normally produced by the wild-type allele, predicting a truncated HESX1 protein. The mutation is likely to cause IGHD in the heterozygous patient by interfering with the downregulation of HESX1 expression mediated by alternative splicing and NMD. Our results open new insight into the mechanism of HESX1 regulation suggesting that the coupling of alternative splicing and NMD might play a fundamental role in directing the HESX1 expression, and that the alteration of this process might lead to severe consequences.

Objective: The aim of the study was to examine clinical characteristics, biochemical parameters, and TSH-R gene variations in children and adolescents with subclinical hypothyroidism (SH) in order to evaluate their pattern of distribution in SH., Patients: We enrolled 88 patients, each having at least two TSH measurements above the upper limit of the reference range with normal free thyroid hormones and negative thyroid autoantibodies., Main Outcome Measures: Clinical characteristics included height, weight, family history of thyroid diseases, thyroid volume, and echogenicity at ultrasonography. Biochemical parameters included TSH, free thyroid hormones, thyroid autoantibodies, and adjusted daily urinary iodine excretion (UIE). Genetic variations in the TSH-R gene were assessed., Results: The prevalence of overweight/obesity, positive family history of thyroid diseases, and thyroid hypoechogenicity was 28.4, 45.5, and 22.7%, respectively. Median TSH was higher in overweight/obese patients than in normal-weight ones (7.4 vs. 5.7 muIU/ml; P = 0.04) and in overweight/obese patients with hypoechogenicity than in those with normal ultrasound pattern (8.5 vs. 6.8 muIU/ml; P = 0.04). Adjusted daily UIE was lower in subjects without than in those with a positive family history of thyroid diseases (81 vs. 120 mug/d; P = 0.001). The prevalence of a positive family history of thyroid diseases was 1.9-fold higher in patients with nonsynonymous mutations in the TSH-R gene than in patients without any mutation (80 vs. 42%; P = 0.03). A novel mutation at position 1559 in exon 10 (W520X) was detected in one child., Conclusions: Overweight/obesity, thyroid hypoechogenicity, and nonsynonymous mutations in the TSH-R gene are characterizing features of a large portion of SH children.

Background/aims: Chronic hepatitis C (CHC) is often associated with auto-immune reactions. In the light of the role of alcohol in promoting CHC progression, we have investigated the possible presence of auto-reactivity against the ethanol-inducible cytochrome P4502E1 (CYP2E1) in CHC patients with and without alcohol consumption., Methods: The IgG reactivity against recombinant human CYP2E1 was evaluated by solid-phase immunoassays in 102 CHC patients with different alcohol consumption and 59 HCV-free controls., Results: Auto-antibodies against CYP2E1 were significantly (p<0.0001) increased in CHC patients as compared to controls. Anti-CYP2E1 IgG above the 97th percentile in the controls were evident in 41 (40%) CHC patients. Competition experiments revealed that CYP2E1 recognition was not due to the cross-reactivity with CYP2D6. The detection of anti-CYP2E1 IgG was unrelated to alcohol consumption and no difference in gender, age, aminotransferase levels and virus genotype was evident among the patients with or without anti-CYP2E1 auto-antibodies. However, anti-CYP2E1 auto-reactivity was significantly (p=0.025) associated with the severity of periportal/periseptal interface hepatitis. Moreover, confocal microscopy demonstrated that anti-CYP2E1 IgG associated with CHC recognized CYP2E1 exposed on the outer side of hepatocyte plasma membranes., Conclusions: HCV infection favours the breaking of self-tolerance against CYP2E1 that might contribute to hepatocyte injury.

Richter's transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA (Max gene associated), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1/Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT. Editor's summary: Richter's transformation (RT) involves the progression of chronic lymphocytic leukemia (CLL) to a more aggressive lymphoma with poor outcomes. Understanding the transition into RT is key to more targeted therapeutic strategies. Iyer et al. examined the role of the MYC suppressor MGA, which is differentially expressed in RT, in an in vivo CLL model with MGA dysfunction. MGA loss resulted in increased mitochondrial function and reactive oxygen species and led to aberrant cell morphology and up-regulated MYC as commonly observed in patients. Combined inhibition of MYC and mitochondrial respiration prolonged in vivo survival in this model, highlighting potential therapeutic strategies for RT with this genetic profile. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Background: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. Methods: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. Results: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. Conclusions: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency. [ABSTRACT FROM AUTHOR]

To understand the neurocognitive mechanisms that underlie heterogeneity in cognitive ageing, recent scientific efforts have led to a growing public availability of imaging cohort data. The Advanced BRain Imaging on ageing and Memory (ABRIM) project aims to add to these existing datasets by taking an adult lifespan approach to provide a cross-sectional, normative database with a particular focus on connectivity, myelinization and iron content of the brain in concurrence with cognitive functioning, mechanisms of reserve, and sleep-wake rhythms. ABRIM freely shares MRI and behavioural data from 295 participants between 18–80 years, stratified by age decade and sex (median age 52, IQR 36–66, 53.20% females). The ABRIM MRI collection consists of both the raw and pre-processed structural and functional MRI data to facilitate data usage among both expert and non-expert users. The ABRIM behavioural collection includes measures of cognitive functioning (i.e., global cognition, processing speed, executive functions, and memory), proxy measures of cognitive reserve (e.g., educational attainment, verbal intelligence, and occupational complexity), and various self-reported questionnaires (e.g., on depressive symptoms, pain, and the use of memory strategies in daily life and during a memory task). In a sub-sample (n = 120), we recorded sleep-wake rhythms using an actigraphy device (Actiwatch 2, Philips Respironics) for a period of 7 consecutive days. Here, we provide an in-depth description of our study protocol, pre-processing pipelines, and data availability. ABRIM provides a cross-sectional database on healthy participants throughout the adult lifespan, including numerous parameters relevant to improve our understanding of cognitive ageing. Therefore, ABRIM enables researchers to model the advanced imaging parameters and cognitive topologies as a function of age, identify the normal range of values of such parameters, and to further investigate the diverse mechanisms of reserve and resilience. [ABSTRACT FROM AUTHOR]

The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) and then prospectively applied to 15 participants (scanned 8–11 times). Analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that linked to distant regions. Third-order networks possessed regions distributed widely throughout association cortex. Regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated across multiple cortical zones. We refer to these as supra-areal association megaclusters (SAAMs). Within each SAAM, two candidate control regions were adjacent to three separate domain-specialized regions. Response properties were explored with task data. The somatomotor and visual networks responded to body movements and visual stimulation, respectively. Second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions dissociated across language, social, and spatial/episodic processing domains. These results suggest that progressively higher-order networks nest outward from primary sensory and motor cortices. Within the apex zones of association cortex, there is specialization that repeatedly divides domain-flexible from domain-specialized regions. We discuss implications of these findings, including how repeating organizational motifs may emerge during development. NEW & NOTEWORTHY: The organization of cerebral networks was estimated within individuals with intensive, repeat sampling of fMRI data. A hierarchical organization emerged in each individual that delineated first-, second-, and third-order cortical networks. Regions of distinct third-order association networks consistently exhibited side-by-side juxtapositions that repeated across multiple cortical zones, with clear and robust functional specialization among the embedded regions. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) lies towards the heteromodal end of the principal gradient of intrinsic connectivity, maximally separated from the sensory‐motor cortex. It supports memory‐based cognition, including the capacity to retrieve conceptual and evaluative information from sensory inputs, and to generate meaningful states internally; however, the functional organisation of DMN that can support these distinct modes of retrieval remains unclear. We used fMRI to examine whether activation within subsystems of DMN differed as a function of retrieval demands, or the type of association to be retrieved, or both. In a picture association task, participants retrieved semantic associations that were either contextual or emotional in nature. Participants were asked to avoid generating episodic associations. In the generate phase, these associations were retrieved from a novel picture, while in the switch phase, participants retrieved a new association for the same image. Semantic context and emotion trials were associated with dissociable DMN subnetworks, indicating that a key dimension of DMN organisation relates to the type of association being accessed. The frontotemporal and medial temporal DMN showed a preference for emotional and semantic contextual associations, respectively. Relative to the generate phase, the switch phase recruited clusters closer to the heteromodal apex of the principal gradient—a cortical hierarchy separating unimodal and heteromodal regions. There were no differences in this effect between association types. Instead, memory switching was associated with a distinct subnetwork associated with controlled internal cognition. These findings delineate distinct patterns of DMN recruitment for different kinds of associations yet common responses across tasks that reflect retrieval demands. [ABSTRACT FROM AUTHOR]

The space-charge-limited-current spectroscopy is a consolidated technique for studying electrical properties of materials and devices. In general, the conduction in the material can be expressed as a single scaling law, relating the current with voltage and gap (or sample thickness) with different values for the exponents. However, some aspects of this technique remain obscure, especially when dealing with very thin (few nanometer) gaps and solids. Beyond this, abrupt transitions between different transport regimes are observed, whereas unusual space-charge-limited current behaviors are expected in out of 2D plane of 2D-material-based heterostructures. Therefore, there is a need for a universal model to describe the current–voltage characteristic curves, including different conduction mechanisms as well as smooth transitions between them. This goal, pursued for decades without substantial success, is not achievable based on the mentioned simple scaling laws, requiring a new approach. In this work, we propose a universal model with the same underlying physics. A new function is considered which contains relevant information for transport and accounts for most of the fingerprints observed in experimental current–voltage curves of the most diverse set of physical systems, from materials to devices. This approach leads to the usual scaling laws for constant values of the transport function, whereas it is abandoned for the trap filling regime, although the same familiar higher slopes of current–voltage curves can be recovered. The model is used to fit the experimental curves of the most diverse materials and devices in order to show its applicability and accuracy. [ABSTRACT FROM AUTHOR]

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3 T and 7 T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3 T vs. 8.5 at 7 T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20–40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research. [ABSTRACT FROM AUTHOR]

Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards. [ABSTRACT FROM AUTHOR]

Data standardization promotes a common framework through which researchers can utilize others' data and is one of the leading methods neuroimaging researchers use to share and replicate findings. As of today, standardizing datasets requires technical expertise such as coding and knowledge of file formats. We present ezBIDS, a tool for converting neuroimaging data and associated metadata to the Brain Imaging Data Structure (BIDS) standard. ezBIDS contains four major features: (1) No installation or programming requirements. (2) Handling of both imaging and task events data and metadata. (3) Semi-automated inference and guidance for adherence to BIDS. (4) Multiple data management options: download BIDS data to local system, or transfer to OpenNeuro.org or to brainlife.io. In sum, ezBIDS requires neither coding proficiency nor knowledge of BIDS, and is the first BIDS tool to offer guided standardization, support for task events conversion, and interoperability with OpenNeuro.org and brainlife.io. [ABSTRACT FROM AUTHOR]

Obesity affects more than one billion people worldwide and often leads to cardiometabolic chronic comorbidities. It induces senescence-related alterations in adipose tissue, and senescence is closely linked to obesity. Fully elucidating the pathways through which vitamin D exerts anti-inflammatory effects may improve our understanding of local adipose tissue inflammation and the pathogenesis of metabolic disorders. In this narrative review, we compiled and analyzed the literature from diverse academic sources, focusing on recent developments to provide a comprehensive overview of the effect of vitamin D on inflammation associated with obesity and senescence. The article reveals that the activation of the NF-κB (nuclear factor kappa B subunit 1) and NLRP3 inflammasome (nucleotide-binding domain, leucine-rich-containing, pyrin domain-containing-3) pathways through the toll-like receptors, which increases oxidative stress and cytokine release, is a common mechanism underlying inflammation associated with obesity and senescence, and it discusses the potential beneficial effect of vitamin D in alleviating the development of subclinical inflammation. Investigating the main target cells and pathways of vitamin D action in adipose tissue could help uncover complex mechanisms of obesity and cellular senescence. This review summarizes significant findings related to opportunities for improving metabolic health. [ABSTRACT FROM AUTHOR]

Affective neuroscience has traditionally relied on cross-sectional studies to uncover the brain correlates of affects, emotions, and moods. Such findings obfuscate intraindividual variability that may reveal meaningful changing affect states. The few functional magnetic resonance imaging longitudinal studies that have linked changes in brain function to the ebbs and flows of affective states over time have mostly investigated a single individual. In this study, we explored how the functional connectivity of brain areas associated with affective processes can explain within-person fluctuations in self-reported positive and negative affects across several subjects. To do so, we leveraged the Day2day dataset that includes 40 to 50 resting-state functional magnetic resonance imaging scans along self-reported positive and negative affectivity from a sample of six healthy participants. Sparse multivariate mixed-effect linear models could explain 15% and 11% of the within-person variation in positive and negative affective states, respectively. Evaluation of these models' generalizability to new data demonstrated the ability to predict approximately 5% and 2% of positive and negative affect variation. The functional connectivity of limbic areas, such as the amygdala, hippocampus, and insula, appeared most important to explain the temporal dynamics of affects over days, weeks, and months., (© 2024. The Author(s).)

Purpose: To investigate longitudinal associations between the vitamin D status and inflammatory markers in children and adolescents., Methods: Children from eight European countries from the IDEFICS/I.Family cohort with repeated measurements were included in this study. A linear mixed-effect model was used to model the association of serum 25(OH)D as independent variable and z-scores of inflammatory markers [CRP, cytokines, adipokines, combined inflammation score] as dependent variables, where one level accounts for differences between individuals and the other for changes over age within individuals., Results: A total of 1,582 children were included in the study. In the adjusted model, 25(OH)D levels were positively associated with adiponectin (β = 0.11 [95% CI 0.07; 0.16]) and negatively with the inflammation score (β = - 0.24 [95% CI - 0.40; - 0.08]) indicating that the adiponectin z-score increased by 0.11 units and the inflammation score decreased by 0.24 units per 12.5 nmol/l increase in 25(OH)D. In children with overweight or obesity, only a positive association between 25(OH)D and IP-10 was observed while in children with normal weight adiponectin was positively and the inflammation score was negatively associated. Associations of vitamin D with adiponectin and the inflammation score were stronger in girls than in boys and a positive association with TNF-α was observed only in girls., Conclusion: Our results suggest that an increase in vitamin D concentrations may help to regulate inflammatory biomarkers. However, it seems to be no benefit of a better vitamin D status in children with overweight/obesity unless their weight is managed to achieve an improved inflammatory marker status., (© 2024. The Author(s).)