A review on the role of extrapolation as basis for paediatric marketing authorization applications of medicines in the EU.

Aims: For new medicines, drug companies obtain regulatory approval on the strategy to generate evidence in the paediatric population, which can be supported by extrapolation of evidence obtained in a reference population. This study investigated whether paediatric marketing authorization applications (PMAAs) supported by extrapolation based on exposure-matching were more successful-i.e.

Obsessive-compulsive symptoms and personal recovery in patients with schizophrenia spectrum disorders: A cross-sectional study.

Background: Obsessive-compulsive symptoms (OCS) frequently co-occur in patients with Schizophrenia Spectrum Disorders (SSD). Patients with SSD and OCS experience increased clinical and social challenges, including diminished quality of life and subjective well-being. However, it is unknown whether co-morbid OCS are associated with personal recovery.

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.

People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells.

Evaluation of Peer Review of Percutaneous Coronary Intervention Operator Performance.

Background: Case-based peer review of percutaneous coronary intervention (PCI) is used by many hospitals for quality improvement and to make decisions regarding physician competency. However, there are no studies testing the reliability or validity of peer review for PCI performance evaluation.

Methods: We recruited interventional cardiologists from 12 Veterans Affairs Health System facilities throughout the United States to provide PCI cases for review.

Sequential Pore Functionalization in MOFs for Enhanced Carbon Dioxide Capture.

The capture of carbon dioxide (CO) is crucial for reducing greenhouse emissions and achieving net-zero emission goals. Metal-organic frameworks (MOFs) present a promising solution for carbon capture due to their structural adaptability, tunability, porosity, and pore modification. In this research, we explored the use of a copper (Cu(II))-based MOF called .

Associations between momentary mental states and concurrent social functioning after remission from first episode psychosis: A HAMLETT ecological momentary assessment study.

Background: Symptom severity and social functioning are important outcomes after first episode psychosis (FEP), yet current evidence about associations between them is inconsistent and lacks (subclinical) momentary insights.

Methods: The current Ecological Momentary Assessment (EMA) study was conducted in 58 people in remission from FEP, as part of the HAMLETT (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment) trial. At baseline, participants were prompted to report momentary mental states and social context 10x/day for eight consecutive days, including psychotic experiences (PEs), motivation/drive and negative affect, that may indicate proxies of (subclinical) psychotic, negative and general affective symptoms, respectively.

Does stigma leave its mark? The interplay between negative effects of perceived stigma with positive effect of self-esteem on long-term social functioning in schizophrenia.

Background: Individuals with schizophrenia commonly experience poor social functioning (SF), influenced by stigmatization and linked to low self-esteem. The intricate role of self-esteem in this context remains insufficiently explored. This study delves into the short and long-term impact of perceived stigma on SF, investigating the mediating or moderating effects of self-esteem and momentary fluctuations in self-esteem.

Exploring the Interactions Between Psychotic Symptoms, Cognition, and Environmental Risk Factors: A Bayesian Analysis of Networks.

Background And Hypothesis: Psychotic disorders (PDs) have huge personal and societal impact, and efforts to improve outcomes in patients are continuously needed. Environmental risk factors (ERFs), especially modifiable risk factors, are important to study because they pose a target for intervention and prevention. No studies have investigated ERFs, cognition, and psychotic symptoms together in a network approach.

The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses.

Purpose: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet many remain without a molecular diagnosis. The Australian Genomics Mitochondrial Flagship, comprising clinicians, diagnostic, and research scientists, conducted a prospective national study to identify the diagnostic utility of singleton genomic sequencing using blood samples.

Methods: A total of 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mitochondrial DNA (mtDNA) sequencing or genome sequencing.

Barriers to implementation of rapid identification and antimicrobial susceptibility testing technologies in the clinical microbiology laboratory: an American perspective.

Clinical microbiology laboratories are responsible for confirming the aetiology of infectious diseases and providing antimicrobial susceptibility testing results. Traditional culture-based testing can be augmented by more rapid testing modalities to provide clinically actionable information as quickly as possible. Despite improvements in patient outcomes, many clinical microbiology laboratories are facing challenges to in-sourcing these technologies.

The role of TRPA1 and TRPV1 in the perception of astringency.

Astringency, commonly described as a drying, roughening, and/or puckering sensation associated with polyphenol-rich foods affects their palatability. While the compounds eliciting astringency are known, its mechanism of action is debated. This study investigated the role of transient receptor potential (TRP) channels A1 and V1 in astringency perception.

"That Looks Like My Kitchen!" - Personalized context by usage frequency and familiarity influences consumer perception and liking of chicken nuggets in VR.

Restoring relevant context during consumer sensory testing using virtual reality (VR) technologies may facilitate evaluations reflective of real-world experiences, enabling reliable data collection to better predict product success. Prior research has applied the same consumption scenario to all participants without accounting for variations in individual consumption habits. Thus, a consumption scenario of low personal relevance can lead to misleading conclusions.

Validation of an automated segmentation method for body composition analysis in colorectal cancer patients using diagnostic abdominal computed tomography images.

Background & Aims: Several automated programs have been developed to facilitate body composition analysis of images from abdominal computed tomography (CT) scans. External validation in patients with colorectal cancer is necessary for use in research and clinical practice. Our aim was to validate an automatic method (AutoMATiCA) of segmenting CT images at the third lumbar level (L3) from patients with colorectal cancer, by comparing with manual segmentation.

The association between height and risk of lung cancer subtypes in men and women in the Netherlands Cohort Study.

Objectives: Previous studies found no or weak positive associations between height and lung cancer (LC) risk, with differences between sexes. Few studies stratified the association by smoking status and LC subtype. This prospective study investigated the association between height and risks of overall LC and LC subtypes (i.

Association between Long-term Energy Balance-Related Factors and Survival in Colorectal Cancer Overall and by Metabolic Warburg-Subtypes.

Background: Long-term energy balance-related factors (i.e., lifestyle and physiologic factors that influence the equilibrium between energy intake and energy expenditure over an extended period) such as body mass index (BMI) are linked to colorectal cancer risk, but their impact on colorectal cancer survival is unclear.

The relationship between Stroma AReactive Invasion Front Areas (SARIFA), Warburg-subtype and survival: results from a large prospective series of colorectal cancer patients.

Background: Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells.

Methods: SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens.

Vitamin B12 Deficiency in Children and Adolescents: A Case for Revised Diagnostic Parameters.

Background: Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications.

Case Summary: Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years.

Materials descriptors for advanced water dissociation catalysts in bipolar membranes.

The voltage penalty driving water dissociation (WD) at high current density is a major obstacle in the commercialization of bipolar membrane (BPM) technology for energy devices. Here we show that three materials descriptors, that is, electrical conductivity, microscopic surface area and (nominal) surface-hydroxyl coverage, effectively control the kinetics of WD in BPMs. Using these descriptors and optimizing mass loading, we design new earth-abundant WD catalysts based on nanoparticle SnO synthesized at low temperature with high conductivity and hydroxyl coverage.

Leukoencephalopathy with calcifications, developmental brain abnormalities and skeletal dysplasia due to homozygosity for a hypomorphic CSF1R variant: A report of three siblings.

We report three siblings homozygous for CSF1R variant c.1969 + 115_1969 + 116del to expand the phenotype of "brain abnormalities, neurodegeneration, and dysosteosclerosis" (BANDDOS) and discuss its link with "adult leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP), caused by heterozygous CSF1R variants. We evaluated medical, radiological, and laboratory findings and reviewed the literature.

A deep intronic variant in MME causes autosomal recessive Charcot-Marie-Tooth neuropathy through aberrant splicing.

Background: Loss-of-function variants in MME (membrane metalloendopeptidase) are a known cause of recessive Charcot-Marie-Tooth Neuropathy (CMT). A deep intronic variant, MME c.1188+428A>G (NM_000902.