Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

Background: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION.

Methods: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm).

Electrically Evoked Stapedius Reflex Measurements in Cochlear Implantation and its Application in the Postoperative Fitting Process.

Measuring the electrically evoked stapedius reflex during the fitting of cochlear implants (CIs) provides a reliable estimation of maximum comfort levels, resulting in the programming of the CI with high hearing comfort and good speech understanding. Detection of the stapedius reflex and the required stimulation level on each implant channel is already being performed during surgery, whereby intraoperative stapedius reflexes are observed through the surgical microscope. Intraoperative stapedius reflex detection is both an indicator that the auditory nerve is responding to electrical stimulation up to the brainstem and a test for the ability to perform postoperative stapedius reflex measurements.

From Chalcogen Bonding to S-π Interactions in Hybrid Perovskite Photovoltaics.

The stability of hybrid organic-inorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of low-dimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions.

Microcystins with Modified Adda-Residues from a Heterologous Microcystin Expression System.

Microcystins are hepatotoxic cyclic heptapeptides produced by some cyanobacterial species and usually contain the unusual β-amino acid 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda) at position-5. The full microcystin gene cluster from PCC 7806 has been expressed in . In an earlier study, the engineered strain was shown to produce MC-LR and [d-Asp]MC-LR, the main microcystins reported in cultures of PCC 7806.

Prevalence and risk factors of intimate partner violence during the COVID-19 pandemic: Results from the population-based study DREAMCORONA.

Objectives: This study examines the 12-month prevalence rates of intimate partner violence (IPV) victimization, including psychological, physical, and sexual forms, in women and men. It also aims to identify changes in IPV victimization during the COVID-19 pandemic and to explore factors associated with the occurrence of any IPV victimization during this period.

Methods: Data from the DREAMCORONA study in Germany collected from May 2020 to February 2021 included 737 participants, i.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings.

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb) children and adults who are at risk of (confirmed single IAb) or living with (multiple IAb) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings.

Neurocomputational Mechanisms Underlying Differential Reinforcement Learning From Wins and Losses in Obesity With and Without Binge Eating.

Background: Binge-eating disorder (BED) is thought of as a disorder of cognitive control, but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations of previous research include a lack of consistent separation between effects of BED and obesity and a disregard for self-report evidence suggesting that neurocognitive alterations may emerge primarily in loss- or harm-avoidance contexts.

Methods: To address these gaps, in this longitudinal study we investigated behavioral flexibility and its underlying neurocomputational processes in reward-seeking and loss-avoidance contexts.

Medication Risks and Their Association with Patient-Reported Outcomes in Inpatients with Cancer.

Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients.

Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire.

Charge Trapping and Defect Dynamics as Origin of Memory Effects in Metal Halide Perovskite Memlumors.

Large language models for artificial intelligence applications require energy-efficient computing. Neuromorphic photonics has the potential to reach significantly lower energy consumption in comparison with classical electronics. A recently proposed memlumor device uses photoluminescence output that carries information about its excitation history via the excited state dynamics of the material.

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry.

With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry.

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders: A Systematic Review and Meta-Analysis.

Importance: Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.

Objective: To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients.

Data Sources: MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses.

Bacillamide D produced by Bacillus cereus from the mouse intestinal bacterial collection (miBC) is a potent cytotoxin in vitro.

The gut microbiota influences human health and the development of chronic diseases. However, our understanding of potentially protective or harmful microbe-host interactions at the molecular level is still in its infancy. To gain further insights into the hidden gut metabolome and its impact, we identified a cryptic non-ribosomal peptide BGC in the genome of Bacillus cereus DSM 28590 from the mouse intestine ( www.

The olfactory diary: Tracking awareness and consciousness of the sense of smell throughout the day.

Objectives: The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell.

Methods: In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin' Sticks.

Gene therapy with phosphodiesterases 2A and 4B ameliorates heart failure and arrhythmias by improving subcellular cAMP compartmentation.

Aims: Gene therapy with cardiac phosphodiesterases (PDEs), such as phosphodiesterase 4B (PDE4B), has recently been described to effectively prevent heart failure (HF) in mice. However, exact molecular mechanisms of its beneficial effects, apart from general lowering of cardiomyocyte cyclic adenosine monophosphate (cAMP) levels, have not been elucidated. Here, we studied whether gene therapy with two types of PDEs, namely PDE2A and PDE4B, can prevent pressure-overload-induced HF in mice by acting on and restoring altered cAMP compartmentation in distinct subcellular microdomains.

Gold Nanoparticles with N-Heterocyclic Carbene/Triphenylamine Surface Ligands: Stable and Electrochromically Active Hybrid Materials for Optoelectronics.

Organic-hybrid particle-based materials are increasingly important in (opto)electronics, sensing, and catalysis due to their printability and stretchability as well as their potential for unique synergistic functional effects. However, these functional properties are often limited due to poor electronic coupling between the organic shell and the nanoparticle. N-heterocyclic carbenes (NHCs) belong to the most promising anchors to achieve electronic delocalization across the interface, as they form robust and highly conductive bonds with metals and offer a plethora of functionalization possibilities.

Gene Methylation Affects Salivary Levels of the Taste Buds' Trophic Factor, Gustin Protein.

The salivary protein, Gustin/carbonic anhydrase VI, has been described as a trophic factor responsible for the growth of taste buds. We found, in a genetically homogeneous population, that the polymorphism (A/G) of the Gustin gene is crucial for the full functionality of the protein and is associated with taste sensitivity. However, other studies have failed to find this evidence.

Efficacy of an Internet- and Mobile-Based Intervention for Subclinical Anxiety and Depression (ICare Prevent) with Two Guidance Formats: Results from a Three-Armed Randomized Controlled Trial.

Introduction: Limited research exists on intervention efficacy for comorbid subclinical anxiety and depressive disorders, despite their common co-occurrence. Internet- and mobile-based interventions (IMIs) are promising to reach individuals facing subclinical symptoms.

Objective: This study aimed to evaluate the efficacy of a transdiagnostic and self-tailored IMI in reducing subclinical anxiety and depressive symptom severity with either individualized (IG-IMI) or automated (AG-IMI) guidance compared to a waitlist control group with care-as-usual access (WLC).

Water status dynamics and drought tolerance of juvenile European beech, Douglas fir and Norway spruce trees as dependent on neighborhood and nitrogen supply.

To increase the resilience of forests to drought and other hazards, foresters are increasingly planting mixed stands. This requires knowledge about the drought response of tree species in pure and mixed-culture neighborhoods. In addition, drought frequently interacts with continued atmospheric nitrogen (N) deposition.

Reducing Abdominal Aortic Aneurysm Progression by Blocking Neutrophil Extracellular Traps Depends on Thrombus Formation.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start.