Genotype-Guided Asthma Treatment Reduces Exacerbations in Children: Meta-Analysis of Two RCTs.

Background: Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment.

Development of the Dutch translational knowledge agenda for inherited metabolic diseases.

Background: Inherited metabolic diseases (IMDs) may have considerable implications for patients and their families. Despite their individual rarity, covering a spectrum of over 1800 distinct diseases, the diseases collectively exert a significant impact, with often lifelong disabilities. The United for Metabolic Diseases consortium was established to catalyze research with translation into the best possible care.

Boron Designer Enzyme with a Hybrid Catalytic Dyad.

Genetically encoded noncanonical amino acids can introduce new-to-nature activation modes into enzymes. While these amino acids can act as catalysts on their own due to their inherent chemical properties, interactions with adjacent residues in an enzyme, such as those present in natural catalytic dyads or triads, unlock a higher potential for designer enzymes. We incorporated a boron-containing amino acid into the protein scaffold RamR to create an active enzyme for the kinetic resolution of α-hydroxythioesters.

Magma Ocean Evolution at Arbitrary Redox State.

Interactions between magma oceans and overlying atmospheres on young rocky planets leads to an evolving feedback of outgassing, greenhouse forcing, and mantle melt fraction. Previous studies have predominantly focused on the solidification of oxidized Earth-similar planets, but the diversity in mean density and irradiation observed in the low-mass exoplanet census motivate exploration of strongly varying geochemical scenarios. We aim to explore how variable redox properties alter the duration of magma ocean solidification, the equilibrium thermodynamic state, melt fraction of the mantle, and atmospheric composition.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Lost and found: dynamics of relationship and employment status over time in people with affective and psychotic spectrum disorders.

Background: Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.

Aims: We investigated employment and relationship status changes among patients across the affective and psychotic spectrum - in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.

Lower risk of revision in fixed-bearing compared to mobile-bearing total ankle arthroplasties: A register based evaluation of 1246 patients in the Netherlands.

Background: Total ankle arthroplasty (TAA) has been developed as treatment for disabling tibiotalar osteoarthritis. TAAs are divided into mobile- and fixed-bearings. The aim was to determine the incidence and trends of fixed- and mobile bearings over time and investigate the association of bearing type and risk of revision after primary TAA in the Netherlands.

Does a Restrictive Diagnostic Work-up for Thyroid Nodules Lead to a Different Papillary Thyroid Cancer Patient Population? A Comparison Between Dutch and U.S. T1-T3 Patient Population.

Introduction: The 2015 American Thyroid Association guidelines recommend de-escalating surgical treatment for papillary thyroid cancer (PTC). We hypothesize that the Dutch PTC population might differ due to a restrictive diagnostic policy that mainly selects symptomatic and palpable thyroid nodules for further diagnostics, potentially selecting relatively more aggressive tumors. We aimed to describe the Dutch PTC population because differences in populations can have consequences for the adoption of foreign guidelines.

Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.

Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce.

Genomic structural equation modeling of reward-related traits: exploring the genetic factor structure and its relationship with psychopathology.

Reward sensitivity has a partial genetic background, and extreme levels may increase vulnerability to psychopathology. This study explores the genetic factor structure underlying reward-related traits and examines how genetic variance links to psychopathology. We modeled GWAS data from ten reward-related traits: risk tolerance (N = 975,353), extraversion (N = 122,886), sensation seeking (N = 132,395), (lack of) premeditation (N = 132,667), (lack of) perseverance (N = 133,517), positive urgency (N = 132,132), negative urgency (N = 132,559), attentional impulsivity (N = 124,739), motor impulsivity (N = 124,104), and nonplanning impulsivity (N = 123,509) to derive their genetic factor structure.

Multiple Sclerosis: Glial Cell Diversity in Time and Space.

Multiple sclerosis (MS) is the most prevalent human inflammatory disease of the central nervous system with demyelination and glial scar formation as pathological hallmarks. Glial cells are key drivers of lesion progression in MS with roles in both tissue damage and repair depending on the surrounding microenvironment and the functional state of the individual glial subtype. In this review, we describe recent developments in the context of glial cell diversity in MS summarizing key findings with respect to pathological and maladaptive functions related to disease-associated glial subtypes.

An atlas of the shared genetic architecture between atopic and gastrointestinal diseases.

Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4 T cells consistently across relevant tissues.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM-HF and PARAGON-HF.

Background: The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.

Unravelling the role of health literacy among individuals with multimorbidity: a systematic review and meta-analysis.

Objective: To examine existing literature regarding health literacy levels and their association with multimorbidity and the potential underlying mechanisms behind the said association.

Design: Systematic review and meta-analysis.

Data Sources: The databases MEDLINE, EMBASE, CINAHL and Science Direct were searched for articles published between 1 January 2000 and 31 October 2023 using a systematic search strategy.

Left atrial strain predicts long-term heart failure outcomes after ST-elevation myocardial infarction.

Background: Left atrial (LA) strain reflects not only LA function but also systolic and diastolic left ventricular function. We therefore hypothesize that LA strain may be a comprehensive predictor of heart failure related endpoints after ST-elevation myocardial infarction (STEMI). We aim to assess the impact of LA reservoir strain on the long-term prognosis following ST-elevation myocardial infarction (STEMI).

Application of the Time-Domain Multichromophoric Fluorescence Resonant Energy Transfer Method in the NISE Programme.

We present the implementation of the time-domain multichromophoric fluorescence resonant energy transfer (TC-MCFRET) approach in the numerical integration of the Schrödinger equation (NISE) program. This method enables the efficient simulation of incoherent energy transfer between distinct segments within large and complex molecular systems, such as photosynthetic complexes. Our approach incorporates a segmentation protocol to divide these systems into manageable components and a modified thermal correction to ensure detailed balance.

Menin inhibitors in the treatment of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the (oligo)clonal expansion of myeloid progenitor cells. Despite advances in treatment, AML remains challenging to cure, particularly in patients with specific genetic abnormalities. Menin inhibitors have emerged as a promising therapeutic approach, targeting key genetic drivers of AML such as KMT2A rearrangements and NPM1 mutations.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Contrasting genetic burden for bipolar disorder: Early onset versus late onset in an older adult bipolar disorder sample.

Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar disorder (PRS-BD), schizophrenia (PRS-SCZ), and major depressive disorder (PRS-MDD) with age of onset in OABD.

Corrigendum: Assessing effectiveness of serious game training designed to assist in upper limb prosthesis rehabilitation.

[This corrects the article DOI: 10.3389/fresc.2024.

The AI Act in a law enforcement context: The case of automatic speech recognition for transcribing investigative interviews.

Law enforcement agencies manually transcribe thousands of investigative interviews per year in relation to different crimes. In order to automate and improve efficiency in the transcription of such interviews, applied research explores artificial intelligence models, including Automatic Speech Recognition (ASR) and Natural Language Processing. While AI models can improve efficiency in criminal investigations, their successful implementation requires evaluation of legal and technical risks.

Physiological versus time based cord clamping in very preterm infants (ABC3): a parallel-group, multicentre, randomised, controlled superiority trial.

Background: Physiological-based cord clamping (PBCC) in preterm infants is beneficial for cardiovascular transition at birth and may optimize placental transfusion. Whether PBCC can improve clinical outcomes is unknown. The aim of the Aeration, Breathing, Clamping (ABC3) trial was to test whether PBCC results in improved intact survival in very preterm infants.

Corrigendum to "Understanding frailty and its opposites from community-dwelling older people's perspectives: A phenomenological qualitative study" [International Journal of Nursing Studies Advances 7 (2024) 100238].

[This corrects the article DOI: 10.1016/j.ijnsa.

Spotlight on the 2024 ESC/EACTS management of atrial fibrillation guidelines: 10 novel key aspects.

Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines.