Emerging strategies, applications and challenges of targeting NAD in the clinic.

Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and efficacy data from NAD-related clinical trials, focusing on aging and neurodegenerative diseases.

The Solve-RD Solvathons as a pan-European interdisciplinary collaboration to diagnose patients with rare disease.

Despite advances in genomic diagnostics, the majority of individuals with rare diseases remain without a confirmed genetic diagnosis. The rapid emergence of advanced omics technologies, such as long-read genome sequencing, optical genome mapping and multiomic profiling, has improved diagnostic yield but also substantially increased analytical and interpretational complexity. Addressing this complexity requires systematic multidisciplinary collaboration, as recently demonstrated by targeted diagnostic workshops.

Improving outcomes in kidney transplantation through advances in donor organ perfusion.

The global shortage of suitable donor kidneys is the primary challenge in kidney transplantation, and it is exacerbated by ageing donors with increased numbers of health issues. Improving organ assessment, preservation and conditioning could enhance organ utilization and patient outcomes. Hypothermic machine perfusion (HMP) is associated with better results than static cold storage by reducing delayed graft function and improving short-term graft survival, especially in kidneys recovered from marginal-quality donors.

Indications for haematopoietic cell transplantation and CAR-T for haematological diseases, solid tumours and immune disorders: 2025 EBMT practice recommendations.

For over two decades, the EBMT has updated recommendations on indications for haematopoietic cell transplantation (HCT) practice based on clinical and scientific developments in the field. This is the ninth special EBMT report on indications for HCT for haematological diseases, solid tumours and immune disorders. Our aim is to provide guidance on HCT indications according to prevailing clinical practice in EBMT countries and centres.

Personalised genomic strategies improve diagnostic yield in inherited retinal dystrophies: a stepwise, patient-centred approach.

Background: Inherited retinal dystrophies (IRDs) are a genetically heterogeneous group of conditions, with approximately 40% of cases remaining unresolved after initial genetic testing. This study aimed to assess the impact of a personalised genomic approach integrating whole-exome sequencing (WES) reanalysis, whole-genome sequencing (WGS), customised gene panels and functional assays to improve diagnostic yield in unresolved cases.

Subjects/methods: We retrospectively reviewed a cohort of 597 individuals with IRDs, including 525 probands and 72 affected relatives.

Transcriptomics and eQTLs reveal inflammatory heterogeneity in the duodenal lining in coeliac disease.

In coeliac disease (CeD), the epithelial lining (EL) of the small intestine is severely damaged by a complex auto-inflammatory response, leading intraepithelial lymphocytes to attack epithelial cells. To understand the intestinal changes and genetic regulation in CeD, we investigated the heterogeneity in the transcriptomic profile of the duodenal EL using RNA-seq and eQTL analysis on predicted cell types. The study included duodenal biopsies from 82 patients, grouped into controls, gluten-free diet treated CeD and untreated CeD.

"For ladies, 35 is check-out time": An anocritical approach to the sitcom Girls5eva.

This article offers an anocritical reading of Girls5eva, a sitcom about a 1990s one-hit girl group trying to make a comeback. Building on scholarship into the representation of aging women in popular media and the music industry, our reading first addresses fuzzy boundaries between life stages and transgressions of the normalized life course. Second, we examine the discourse of girl power and its relationship to midlife transformation.

Phasic alertness impairs cognitive control by amplifying competition between evidence accumulators.

Although phasic alertness generally benefits cognitive performance, it often increases the impact of distracting information, resulting in impaired decision-making and cognitive control. However, it is unclear why phasic alertness has these negative effects. Here, we present a novel, biologically-informed account, according to which phasic alertness generates a transient, evidence-independent input to the decision process.

Spiritual Support for People Affected by Dementia: A Scoping Review.

As a life-limiting illness, dementia requires a holistic approach to care, where spiritual support plays a crucial role in helping individuals and their caregivers find meaning and solace. Our aim was to systematically map the research conducted on psychosocial interventions developed to provide spiritual support for people living with dementia and their caregivers from diagnosis and across the disease trajectory. A scoping review was conducted to explore the breadth of research on 'spiritual support' in dementia care, encompassing interventions, service delivery models, programs, toolkits, approaches, and activities.

Smoking at football clubs: the Netherlands compared to Germany.

Ideally, in a smoke-free generation, children could practice sports in a smoke-free setting. This article studied the prevalence of smoking at football clubs in two countries. An audit at 45 German and 116 Dutch clubs measured smoking prevalence at three places.

Multilayer thin-film produces recurrent evolution of iridescence in mammals.

Iridescent coloration is a vibrant structural colour that is widespread in nature, but in mammals is thought to be limited. Although multiple rodent and Eulipotyphlan species have been anecdotally described as iridescent, empirical evidence outside of the Chrysochloridae (golden mole) family is lacking. As iridescence in golden moles is created through a thin-film mechanism from a compressed cuticle structure, and the structure of hair is highly conserved, we expect iridescence to be present, and produced by the same mechanism, in mammals that share similar hair properties.

Seasonal variation in SARS-CoV-2 transmission in The Netherlands, 2020-2022: statistical evidence for an inverse association with solar radiation and temperature.

In temperate regions, respiratory viruses such as SARS-CoV-2 are better transmitted in winter than in summer. Understanding how the weather is associated with SARS-CoV-2 transmissibility can enhance projections of COVID-19 incidence and improve estimation of the effectiveness of control measures. During the pandemic, transmissibility was tracked by the reproduction number .

Artificial Intelligence in allergy and immunology: recent developments, implementation challenges, and the road towards clinical impact.

Artificial intelligence (AI) is increasingly recognized for its capacity to transform medicine. While publications applying AI in allergy and immunology have increased, clinical implementation substantially lags behind other specialties. By mid-2024, over 1,000 FDA-approved AI-enabled medical devices existed, but none specifically addressed allergy and immunology.

Infliximab and ustekinumab clearance better predict endoscopic outcomes than trough concentrations in Crohn's disease.

Background And Aims: Infliximab and ustekinumab clearance have been suggested as predictors of disease activity in patients with inflammatory bowel diseases. We aimed to investigate the benefits of clearance monitoring for predicting endoscopic outcomes in patients with Crohn's disease (CD).

Methods: Data from patients with moderate-to-severe CD starting infliximab (n=108) and ustekinumab (n=80) therapy were repurposed.

Systematic Review of Experimental Studies in Humans on Transcranial Temporal Interference Stimulation.

Transcranial temporal interference stimulation (tTIS) has recently emerged as a non-invasive neuromodulation method aimed at reaching deeper brain regions than conventional techniques. However, many questions about its effects remain, requiring further experimental studies. This review consolidates the experimental literature on tTIS's effects in the human brain, clarifies existing evidence, identifies knowledge gaps, and proposes future research directions to evaluate its potential.

A clinical and genotype-phenotype analysis of MACF1 variants.

Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this domain result in a distinctive cortical and brain stem malformation.

Novel bacterial strategy to hijack plant immunity through metabolic manipulation.

In this issue of Developmental Cell, Yuan et al. explores how the pathogenic bacterium Pseudomonas syringae modulates plant metabolism, particularly through methylglyoxal (MG) accumulation, to suppress immune responses in Arabidopsis. By affecting key proteins TTM2 and CAT2, the pathogen reduces hydrogen peroxide levels, weakening plant defense mechanisms and promoting infection.

Effectiveness of multisensory stimulation and priming (MuSSAP) upper limb training in 3-8 months old infants with unilateral brain lesion - a retrospective clinical cohort study.

Introduction: Multi Sensory Stimulation And Priming (MuSSAP) is an early upper limb training for infants at high risk of unilateral cerebral palsy (CP). MuSSAP is designed to enhance awareness of the affected upper limb facilitating initiation of goal-directed movements. This study assesses the effectiveness of an 8-week MuSSAP training on manual ability in a clinical setting.