Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Risankizumab Efficacy and Safety Based on Prior Inadequate Response or Intolerance to Advanced Therapy: Post Hoc Analysis of the INSPIRE and COMMAND Phase 3 Studies.

Background And Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).

Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo.

Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.

Objective: Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown.

Methods: Plasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to mass spectrometry.

Identification of a circulating carbohydrate antigen as a highly specific and sensitive target for schistosomiasis serology.

Unlabelled: The World Health Organization (WHO) 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production.

Age-associated differences in FIRES: Characterizing prodromal presentation and long-term outcomes via the web-based NORSE/FIRES Family Registry.

Febrile infection-related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web-based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long-term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti-seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES.

Egg allergen-specific T-cell and cytokine responses in healthy and egg-allergic children naturally tolerating baked egg.

Background: Type 1 regulatory T (Tr1) cells are critical players in maintaining peripheral tolerance, by producing high IL-10 levels in association with inducible T-cell co-stimulator (ICOS) expression. Whether these cells play a role in naturally acquired baked egg tolerance is unknown.

Objectives: Evaluate frequencies of egg-responsive Tr1 and Th2 cells in egg-allergic children that naturally acquired baked egg tolerance (BET) versus non-egg-allergic (NEA) children.

Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy.

Recently, avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV). Avacopan is an inhibitor of the C5a-receptor, which plays an important role in chemotaxis and the amplification loop of inflammation in AAV. In the most recent, international guidelines avacopan is recommended as steroid-sparing agents for the management of AAV.

Practical Considerations for the rapid titration of VNS.

For patients with drug-resistant epilepsy who are not candidates for epilepsy surgery, Vagus nerve stimulation (VNS) is the most widely available neuromodulation option and has been available in several countries for 30 years. Given its broad availability and extended history on the market, many healthcare providers (HCPs) have developed individualized practice habits regarding the titration and dosing of VNS. This study provides novel evidence to describe the extent to which VNS management differs among providers and discusses recent literature that indicates how unique programming approaches may impact patient outcomes.

Fit for purpose testing and independent GMP validation of the monocyte activation test.

The present study describes the "fit for purpose" testing and the independent product-specific GMP validation of the monocyte activation test (MAT) to detect pyrogenic and pro-inflammatory contaminants, MAT Method A, Quantitative Test (European Pharmacopoeia, Ph. Eur. chapter 2.

Variations in linear energy transfer distributions within a European proton therapy planning comparison of paediatric posterior fossa tumours.

Background And Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres.

The Cost of Regulating Effort: Reward and Difficulty Cues With Longer Prediction Horizons Have a Stronger Impact on Performance.

Many theories on cognitive effort start from the assumption that cognitive effort can be expended at will, and flexibly up- or down-regulated depending on expected task demand and rewards. However, while effort regulation has been investigated across a wide range of incentive conditions, few investigated the cost of effort regulation itself. Across four experiments, we studied the effects of reward expectancy and task difficulty on effort expenditure in a perceptual decision-making task (random-dot-motion) and a cognitive control task (colour-naming Stroop), and within each task comparted cues between short (cueing the next trial) and long (cueing the next six trials) prediction horizons.

The Role of Morphological Information in Processing Pseudo-words in Italian L2 Learners: It's a Matter of Experience.

The productive use of morphological information is considered one of the possible ways in which speakers of a language understand and learn unknown words. In the present study we investigate if, and how, also adult L2 learners exploit morphological information to process unknown words by analyzing the impact of language proficiency in the processing of novel derivations. Italian L2 learners, divided into three proficiency groups, participated in a lexical decision where pseudo-words could embed existing stems (e.

How to Run Linear Mixed Effects Analysis for Pairwise Comparisons? A Tutorial and a Proposal for the Calculation of Standardized Effect Sizes.

This tutorial provides guidelines for conducting linear mixed effects (LME) analyses for simple designs, aimed at researchers familiar with t-tests, analysis of variance (ANOVA) and linear regression. First, we compare LME analyses with traditional methods when participants are the only source of random variation. We show that LME analysis is more interesting as soon as you have more than one observation per participant per condition.

From knife to needle - the trend of vascular neurosurgery in Belgium.

Introduction: The management of neurovascular pathologies has changed globally over the last few decades. Endovascular treatments are increasing, and fewer surgical procedures are performed.

Research Question: Evaluate the evolution of vascular neurosurgery in Belgium over the last 30 years and compare with other countries.

Recommendations on the management of meningioma and sex hormone therapy: The results of a collaborative effort between neurosurgical, endocrine and gynecological societies.

Introduction: Exogenous and endogenous sex hormones, especially Progesterone agonists, may be causally linked to meningioma progression. Cessation of treatment leads to stabilization or regression of Progestin-induced meningioma. In many cases, avoiding sex hormone therapy may be possible in the context of meningioma treatment.

A Systematic Review on the Evolution of Power Analysis Practices in Psychological Research.

Performing hypothesis tests with adequate statistical power is indispensable for psychological research. In response to several large-scale replication projects following the replication crisis, concerns about the root causes of this crisis - such as questionable research practices (QRPs) - have grown. While initial efforts primarily addressed the inflation of the type I error rate of research due to QRPs, recent attention has shifted to the adverse consequences of low statistical power.

Direct measurement of three different deformations near the ground state in an atomic nucleus.

Atomic nuclei serve as prime laboratories for investigations of complex quantum phenomena, where minor nucleon rearrangements cause significant structural changes. Pb is the heaviest known neutron-deficient Pb isotope that can exhibit three distinct shapes: prolate, oblate, and spherical, with nearly degenerate excitation energies. Here we report on the combined results from three state-of-the-art measurements to directly observe these deformations in Pb.

A Standardized Classification Scheme for Gastroduodenal Disorder Evaluation Using the Gastric Alimetry System: Prospective Cohort Study.

Background And Aims: Gastric Alimetry™ (Alimetry, New Zealand) is a new clinical test for gastroduodenal disorders involving simultaneous body surface gastric electrical mapping and validated symptom profiling. Studies have demonstrated a range of distinct pathophysiological profiles, and a classification scheme is now required. We used Gastric Alimetry spectral and symptom profiles to develop a mechanism-based test classification scheme, then assessed correlations with symptom severity, psychometrics, and quality of life.

Early Endoscopic Outcomes After Risankizumab Are Associated With Fewer Hospitalizations and Surgeries in Crohn's Disease.

Background And Aims: We evaluated the association between endoscopic outcomes following risankizumab induction and subsequent rates of hospitalization and surgery through 52 weeks of risankizumab (both doses) maintenance therapy in patients with Crohn's disease (CD).

Methods: Patients with moderately to severely active CD and clinical response to 12-week risankizumab induction were rerandomized to continued therapy or drug withdrawal in the phase 3 FORTIFY maintenance trial. Incidence rates (events/100 person-years) of CD-related hospitalization and surgery, and the composite of both, through 52 weeks of maintenance were compared between patients achieving vs not achieving predefined endoscopic outcomes following induction.

The Minimum Dietary Diversity For Women Indicator Can Be Extended To Children And Adolescents aged 4-15 Years As A Proxy Population Indicator For Good Micronutrient Adequacy Of Diets In Low- and Middle-Income Countries.

Background: The response to the global call for more data on children's and adolescents' diets and nutrition is limited by the lack of straightforward practical indicators to track their diet quality. On the basis of a food group score compiled from 10 food groups (FGS-10), the minimum dietary diversity for women, calculated as FGS-10 ≥ 5, is a validated proxy population indicator for better micronutrient intake adequacy for adult women in low- and middle-income countries (LMICs).

Objectives: This study aims to validate FGS-10 and its related cutoffs against micronutrient intake adequacy in 4-15-y-old children/adolescents in LMICs.

Selecting repetitive focal and rotational activation patterns with the highest probability of being a source of atrial fibrillation.

Introduction: Repetitive focal and rotational activation patterns are currently used as additional ablation targets for atrial fibrillation (AF). However, there is no evidence that all these detected targets are actual sources of AF. In this paper, we present an approach that detects and ranks AF activation patterns not only based on the degree of pattern repetitiveness but also on the extent to which they are able to entrain their vicinity.

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes.

Early rebleeding rate following endoscopic treatment of colonic diverticular bleeding: a systematic review and meta-analysis.

Background: Various endoscopic treatment options are available for managing colonic diverticular bleeding (CDB). We conducted a systematic review and meta-analysis to assess the effectiveness of these endoscopic interventions in achieving hemostasis in patients with CDB, focusing on early rebleeding rate (ERR) within 30 days.

Methods: A systematic literature search of the PubMed and Cochrane Library databases was performed for articles published between January 2008 and December 2023.

Circulating autophagy regulator Rubicon is linked to increased myocardial infarction risk.

Background: The identification of new biomarkers that improve existing cardiovascular risk prediction models for acute coronary syndrome is essential for accurately identifying high-risk patients and refining treatment strategies. Autophagy, a vital cellular degradation mechanism, is important for maintaining cardiac health. Dysregulation of autophagy has been described in cardiovascular conditions such as myocardial ischemia-reperfusion injury, a key factor in myocardial infarction (MI).

Transcatheter mitral valve repair with MitraClip® enabling single lung transplantation: A case report.

Post-capillary hypertension resulting from mitral regurgitation is typically considered a contraindication for single lung transplantation due to heightened risks of primary graft dysfunction. This case report highlights a 66-year-old COPD patient with severe mitral regurgitation who was deemed ineligible for surgical mitral replacement. As an alternative, transcatheter mitral valve replacement was successfully performed, resulting in the normalization of pulmonary artery pressures.