Consortium profile: the methylation, imaging and NeuroDevelopment (MIND) consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

Virtual Reality as a Window into Sibling Aggression.

Sibling aggression is the most common form of domestic violence, which can have a negative impact on both child and adolescent mental health. The few previous studies that investigated aggression between siblings, assessed aggression primarily through self- or parent-report, with the limitation of reporter bias. The current study examined whether an interactive Virtual Reality (VR) experiment can provide a valid assessment of adolescents' aggressive responses towards their sibling by testing congruence with other similar measures and by examining associations of known risk factors for sibling aggression with the aggression observed in the VR experiment.

European survey on metabolic and cardiovascular risk in Cushing syndrome.

Background: Cushing's syndrome (CS) is associated with increased metabolic and cardiovascular (CV) risk factors and morbidities. Evidence-based guidelines for the management of these issues in active or remitted CS are not available, so best practice is derived from guidelines developed for the general population. We aimed to evaluate the awareness and practice variation for CV comorbidities of CS across Reference Centres (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN).

Mapping advance care planning and advance directives in Latin America.

Background/aims: The extent to which low- and middle-income countries have implemented Advance Care Planning (ACP) and Advance Directives (AD) remains unclear. We aimed to map the current status of ACP/AD in Latin America.

Methods: This cross-sectional, mixed-methods survey of ACP/AD in LA comprised interviews with 18 key informants from 18 out of 20 countries, most of whom were appointed by national Palliative Care Associations.

Identification of robust associations between admission microbiome profiles and complications of acute pancreatitis.

Objective: Patients with acute pancreatitis show reduced gut microbiome diversity and high abundance of pathogenic bacteria compared with healthy subjects. Admission microbiome profiles are increasingly linked to severity, but methodology and study quality hamper interpretation. Our aim was to investigate whether admission microbiome analysis provides robust and reproducible associations with severity and complications of acute pancreatitis.

Neural substrates for the encoding of the contextual tonal alternation: An fNIRS study of Mandarin third-tone sandhi in word production.

Phonological alternations are common in speech, but the neurocognitive mechanisms for their encoding during word production remain unclear. Mandarin Tone 3 sandhi is an example of phonological alternation, whereby the Tone 3 (T3), a low-dipping tone, changes to a Tone 2 (T2)-like rising tone when followed by another T3. Previous research indicates that both the underlying tonal category and the surface tonal variant are activated during T3 sandhi word production, but the neural substrates of these sub-processes remain unclear.

Sensitivity of Different Clinical Outcome Measures in Assessing Adults With Becker Muscular Dystrophy: A 3-Year Natural History Study.

Background And Objectives: Slow and highly variable disease progression in Becker muscular dystrophy (BMD) stresses the need to develop sensitive outcome measures for clinical trials. We evaluated responsiveness of different outcome measures in adult patients with BMD over 3 years and explored if the sensitivity of outcome measures can be increased by selecting on phenotype or genotype.

Methods: Genetically confirmed patients with BMD were recruited via the Dutch Dystrophinopathy Database.

Joint models reveal human subcortical underpinnings of choice and learning behavior.

Decision making and learning processes together enable adaptive strategic behavior. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterized. Here, we study choice and learning processes in the human subcortex, using a tailored ultra-high field 7T functional MRI protocol combined with joint models.

Risk factors and leprosy incidence among contacts in Bangladesh: A multilevel analysis.

Background: The Maltalep trial in Bangladesh assessed whether single-dose rifampicin (SDR) given 8-12 weeks after bacillus Calmette-Guérin (BCG) vaccination was able to prevent excess leprosy cases due to BCG in contacts of newly diagnosed leprosy patients. After previous publication of the two years follow-up results of the trial, we now review the results after five years. Furthermore, to better understand the long-term protective effects of BCG against leprosy, we conduct post-hoc in-depth secondary statistical analyses based on the prospective interventional (randomized) Maltalep trial and a non-interventional (non-randomized) cohort study that was conducted simultaneously in the same project area.

Cell-cell separation device: A new approach to measuring intercellular detachment forces.

Whether at the molecular or cellular scale in organisms, cell-cell adhesion adapts to external mechanical cues arising from the static environment of cells and from dynamic interactions between neighboring cells. Cell-cell adhesion needs to resist detachment forces to secure the integrity and internal organization of organisms. In the past, various techniques have been developed to characterize adhesion properties of molecules and cells in vitro and to understand how cells sense and probe their environment.

A Novel Maturation Equation for Hepatic Clearance Across Preterm, Term Neonates, Children, and Adults: Application to Paracetamol and Its Metabolite.

A preterm and term neonate to adult (PTNA) maturation equation was introduced recently to describe the glomerular filtration rate maturation from birth to adulthood for neonates of varying gestational age. This study aims to evaluate the newly developed PTNA equation against common maturation approaches like allometric scaling (AS0.75), the AS0.

State Anxiety Modulates Conflict Control Depending on Cognitive Control Context: Evidence From Behavioral and ERP Data.

The impact of state anxiety on conflict control and its neural mechanisms, particularly in relation to proactive versus reactive control, remains incompletely understood. Therefore, we conducted two experiments to investigate how state anxiety affects conflict control across different control contexts and to explore the associated temporal dynamics. The threat of shock paradigm was employed to induce state anxiety.

Leftists and Rightists Differ in Their Cardiovascular Responses to Changing Public Opinion on Migration.

People may feel stressed when engaging with contentious topics, such as migration. However, when individuals learn that their opinion-based ingroup is growing or shrinking, they may experience this stress in different ways, namely as a threat or a challenge. In a preregistered study (N = 203 Dutch university students), we examined among host society members how progressive and conservative changes (vs.

Specific features of immune ageing are detected in the earliest stages in rheumatoid arthritis development.

Background: Rheumatoid arthritis is an age-related disease displaying features of an aged immune system. This study aims to determine premature presence of immune ageing in the early stages of RA development, including in patients with clinically suspected arthralgia and undifferentiated arthritis.

Methods: We recruited 224 participants: 69 healthy controls (mean age 57.

Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia.

Background And Objectives: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition.

Effects of s-ketamine and midazolam on respiratory variability: A randomized controlled pilot trial.

S-ketamine and midazolam are frequently used to provide sedation while maintaining spontaneous respiration. However, the effects of these agents on respiratory variability, which reflects the adaptability of the respiratory system, have not been thoroughly explored. We evaluated these effects in a randomized controlled pilot trial.

A brain-wide map of neural activity during complex behaviour.

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with previous expectations to initiate movements and make decisions. It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here we report a comprehensive set of recordings from 621,733 neurons recorded with 699 Neuropixels probes across 139 mice in 12 laboratories.

Brain-wide representations of prior information in mouse decision-making.

The neural representations of prior information about the state of the world are poorly understood. Here, to investigate them, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with a prior probability alternating between 0.

Nutrients drive the antibiotic-specific evolution of resistance in Pseudomonasaeruginosa.

Pseudomonas aeruginosa can exploit its metabolic flexibility during cystic fibrosis lung infections to reduce antibiotic sensitivity and offset resistance costs, traits that influence its evolutionary trajectory. Although both traits are linked to nutrient conditions, their role in resistance evolution remains poorly defined. We examined how single-nutrient conditions influence resistance evolution in P.

Overcoming the barriers to treatment of rare cancer patients in the era of precision oncology: A call to action.

Rare cancers account for a quarter of cancer diagnoses in Europe yet clinical research, diagnosis, treatment access, and survival outcomes lag significantly behind common cancers. Despite the potential of precision oncology, the consistent implementation of comprehensive genomic profiling in routine clinical practice and robust evidence-generation remains a challenge in this population, compounded by regulatory hurdles and a lack of investment in drug development. A concerted effort across all stakeholders is required to optimise diagnostics, including access to molecular profiling, to expedite clinical trials and treatment access, and to gather high-quality data, including patient-reported outcomes, in rare cancers.

Cell Type-Specific Expression of Long Noncoding RNAs in Human Diabetic Kidneys Identifies TARID as a Key Regulator of Podocyte Function.

This study provides a resource for kidney (cell type-specific) long noncoding (lnc)RNA expression and demonstrates the importance of lncRNAs in renal health. We identified 174 cell type-specific lncRNAs in the human kidney, with 54 showing altered expression in diabetic kidney disease. TCF21 antisense RNA inducing promoter demethylation (TARID), a podocyte-specific lncRNA upregulated in diabetic kidney disease, is crucial for actin cytoskeleton reorganization in podocytes.

Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.

Aggregation of RNA-binding proteins (RBPs) is a hallmark of several age-related neuromuscular diseases. However, our understanding of how these aggregates drive dysfunction is often limited by the use of non-disease-relevant models. Oculopharyngeal muscular dystrophy (OPMD) is caused by a short alanine expansion mutation in the PABPN1 gene, which leads to nuclear aggregation of the protein.

Manipulating anthracyclines for deeper tissue penetration and implications for glycolytic tissues.

How drugs penetrate tissues is poorly understood yet important, since drugs that fail to reach their target will be ineffective. We followed the fate of anthracycline cancer drugs at high resolution by exploiting their intrinsic fluorescence. In a cell-based spheroid model, the soluble compound fluorescein penetrates the entire spheroid, unlike hydrophobic fluorescent lipids, which only enter the outermost cell layer.

Time-varying impact of established prognostic factors in resected pancreatic ductal adenocarcinoma.

Background: Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors in PDAC is time-varying.