Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS).

Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial.

Objective: To assess clinical outcomes in patients from BOREAS by emphysema status.

Methods: Patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks.

Soft Tissue Changes at the Pontic Sites of Cantilever Zirconia Ceramic Resin-Bonded Fixed Dental Protheses in the Esthetic Zone: A Clinical Observational Study.

Objective: Data on the stability of soft tissues at pontic sites of resin-bonded fixed dental protheses (RBFDP) are lacking. The purpose of this study was to evaluate soft tissue changes at pontic sites of cantilever zirconia ceramic RBFDPs with and without surgical pretreatment after different follow-up periods in the esthetic zone.

Materials And Methods: Impressions were taken after the insertion of the restorations and an intraoral scan was performed at follow-up examinations.

Early Flowering and Maturity Promote the Successful Adaptation and High Yield of Quinoa ( Willd.) in Temperate Regions.

Quinoa ( Willd.) can offer an alternative for staple food considering its tolerance to abiotic stresses and high seed quality. However, its cultivation in temperate regions has not been successful due to its photoperiod sensitivity and low seed yield.

Regulatory Peptide Pro-Gly-Pro Accelerates Neuroregeneration of Primary Neuroglial Culture after Mechanical Injury in Scratch Test.

The scratch test is used as an experimental in vitro model of mechanical damage to primary neuronal cultures to study the mechanisms of cell death in damaged areas. The involvement of NMDA receptors in processes leading to delayed neuronal death, due to calcium dysregulation and synchronous mitochondrial depolarization, has been previously demonstrated. In this study, we explored the neuroregenerative potential of Pro-Gly-Pro (PGP)-an endogenous regulatory peptide with neuroprotective and anti-inflammatory properties and a mild chemoattractant effect.

Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors.

The DNA repair protein PARP-1 emerged as a valuable target in the treatment of tumor entities with deficiencies of , such as breast cancer. More recently, the application of PARP inhibitors (PARPi) such as olaparib has been expanded to other cancer entities including colorectal cancer (CRC). We previously demonstrated that PARP-1 is overexpressed in human CRC and promotes CRC progression in a mouse model.

Calcification in sea urchin larvae is associated with low metabolic costs.

The energetic costs of generating calcium carbonate skeletons and shells in marine organisms remain largely speculative because of the scarcity of empirical data. However, this information is critical for estimating energetic limitations of marine calcifiers that can explain their sensitivity to changes in sea water carbonate chemistry in past, present and future marine systems. Here, the cost of calcification was evaluated using larval stages of the purple sea urchin, Strongylocentrotus purpuratus.

Insular monoaminergic deficits in prodromal α-synucleinopathies.

Methods: This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB.

Influence of different sample preparation approaches on proteoform identification by top-down proteomics.

Top-down proteomics using mass spectrometry facilitates the identification of intact proteoforms, that is, all molecular forms of proteins. Multiple past advances have lead to the development of numerous sample preparation workflows. Here we systematically investigated the influence of different sample preparation steps on proteoform and protein identifications, including cell lysis, reduction and alkylation, proteoform enrichment, purification and fractionation.

Does Injectable Platelet-Rich Fibrin Combined With Autogenous Demineralized Dentine Enhance Alveolar Ridge Preservation? A Randomized Controlled Trial.

Objective: The present trial evaluated the first-time application of autogenous demineralized dentin graft with injectable platelet-rich fibrin (ADDG + i-PRF) versus autogenous demineralized dentin graft (ADDG), in alveolar ridge preservation (ARP) in the maxillary aesthetic zone.

Material And Methods: Twenty-two maxillary (n = 22) non-molar teeth indicated for extraction were randomized into two groups (n = 11/group). Extracted teeth were prepared into ADDG, implanted into extraction sockets with or without i-PRF amalgamation and covered by collagen sponge.

Paired coral Sr/Ca and δO records reveal increasing ENSO influence on Malaysian Borneo's hydroclimate.

The El Niño Southern Oscillation (ENSO) is a worldwide climate phenomenon impacting temperatures and precipitation regimes across the globe. Previous studies have shown this climate phenomenon to influence Malaysian Borneo's hydroclimate. In the context of a changing climate and increasingly strong extreme ENSO events, understanding the influence of ENSO on this region, and its evolution through time, is essential to better constrain the future impacts it will have on the Maritime Continent's hydroclimate.

Dupilumab Induces Long-Term On-Treatment Clinical Remission in Patients With Type 2 Asthma.

Background: Remission is proposed as a multicomponent outcome for patients with severe asthma.

Objective: This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids.

Clinical and radiological outcome of extended lateral approach via epicondyle osteotomy in complex lateral tibia plateau fractures involving the central and postero-lateral segments.

Introduction: The purpose of this study was to evaluate the clinical and radiological results of complex lateral tibial plateau fractures involving the central segments of the lateral tibial plateau. It was hypothesized that an extended lateral approach by using the lateral epicondyle osteotomy improves the rate of malreduction and yields to good and excellent clinical results at a mid-term follow-up.

Methods: This retrospective case series conducted at two centers evaluated complex lateral tibial plateau fractures treated with an extended lateral approach by lateral epicondyle osteotomy.

Nutritional value and environmental aspects of high-protein ultra-processed foods on the German market.

Objective: To compare nutritional value and aspects with environmental impact of high-protein (HP) and 'normal-protein' (NP) ultra-processed foods (UPF).

Design: 299 HP and 286 NP products were evaluated regarding aspects of nutritional value, energy density, Nutri-Score, number of additives as well as hyper-palatability and price. Environmental impact of HP UPF was addressed by analysing protein sources and the use of environmentally persistent non-nutritive artificial sweeteners.

Synthesis and characterization of core-shell magnetic molecularly imprinted polymer nanocomposites for the detection of interleukin-6.

Interleukin-6 (IL-6) belongs to the cytokine family and plays a vital role in regulating immune response, bone maintenance, body temperature adjustment, and cell growth. The overexpression of IL-6 can indicate various health complications, such as anastomotic leakage, cancer, and chronic diseases. Therefore, the availability of highly sensitive and specific biosensing platforms for IL-6 detection is critical.

as an Alternative Model to Higher Organisms for In Vivo Lung Research.

COPD and asthma are lung diseases that cause considerable burden to more than 800 million people worldwide. As both lung diseases are so far incurable, it is mandatory to understand the mechanisms underlying disease development and progression for developing novel therapeutic approaches. Exposures to environmental cues such as cigarette smoke in earliest life are known to increase disease risks in the individual's own future.

Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics.

Background: Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence.

Methods: We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort.

Molecular Fractionation of Ancient Organic Compounds in Deeply Buried Halite Crystals.

The molecular fractionation of organic compounds through adsorption in minerals has wide implications, including tracing the origins of life, carbon sequestration, and climate change. Here we present the first in situ examination of molecular fractionation within individual crystals via optical-photothermal infrared (O-PTIR) spectroscopy. Our study focuses on a unique inclusion trail within deeply buried halite crystals, characterized by a distinctive orange-to-blue fluorescence gradient, providing primary evidence of molecular variation in ancient carbon-based fluids within the inclusion trail.

An array of Zymoseptoria tritici effectors suppress plant immune responses.

Zymoseptoria tritici is the most economically significant fungal pathogen of wheat in Europe. However, despite the importance of this pathogen, the molecular interactions between pathogen and host during infection are not well understood. Herein, we describe the use of two libraries of cloned Z.