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Abstract Over-use of SABA is associated with poor asthma control and greater risk of exacerbations and death. Identifying and addressing the beliefs driving SABA over-reliance is key to reducing over-use. This study aimed to assess the utility, impact and acceptability of the Reliever Reliance Test (RRT), a brief patient self-test behaviour-change tool to identify and address SABA over-reliance. Patients with asthma who completed the RRT in Argentina were invited to an online survey exploring the acceptability of the RRT, and its impact on patients’ perceptions of SABA and intention to discuss asthma treatment with a doctor. 93 patients completed the questionnaire. The RRT classified 76/93 (82%) as medium-to-high risk of SABA over-reliance (a mindset where SABA is perceived as the most important aspect of asthma treatment), with 73% of these reporting SABA overuse (3 or more times a week). 75% intended to follow the RRT recommendations to review their asthma treatment with their doctor. The RRT is acceptable to patients and was effective at raising awareness of, identifying and addressing SABA over-reliance and encouraging patients to review their treatment with their doctor.

Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively. Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability. Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels. Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Abstract Current evidence suggests that macroalgal-dominated habitats are important contributors to the oceanic carbon cycle, though the role of those formed by calcifiers remains controversial. Globally distributed coralline algal beds, built by pink coloured rhodoliths and maerl, cover extensive coastal shelf areas of the planet, but scarce information on their productivity, net carbon flux dynamics and carbonate deposits hampers assessing their contribution to the overall oceanic carbon cycle. Here, our data, covering large bathymetrical (2–51 m) and geographical ranges (53°N–27°S), show that coralline algal beds are highly productive habitats that can express substantial carbon uptake rates (28–1347 g C m−2 day−1), which vary in function of light availability and species composition and exceed reported estimates for other major macroalgal habitats. This high productivity, together with their substantial carbonate deposits (0.4–38 kilotons), renders coralline algal beds as highly relevant contributors to the present and future oceanic carbon cycle.

In Italy alone, dozens of abandoned holiday camps for children are scattered throughout the landscape. The size and diffusion of this heritage calls for a scientific debate on the history and future of these buildings, which are often in a state of serious decay. From Alpine valleys to coastlines, former holiday camps for children tell a long story of educational, architectural, health and social experimentation, which has influenced generations of Europeans in the last 150 years. Holiday camps were hosted in traditional or modern structures, built from long-lasting materials such as reinforced concrete or temporary camping tents. Whatever their nature, holiday camps have left both physical and intangible traces on the European landscape and society. With this issue, in_bo engages in a debate on the history of holiday camps in Europe between the nineteenth and twentieth centuries, with particular consideration of contemporary reuse and restoration strategies of this architectural heritage.

Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 (n = 1023), we observed 22 and 31 methylation markers associated (FDR P ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 (n = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis-meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.

Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Little is known about immune checkpoint inhibitor activity in the central nervous system, especially in patients receiving monotherapy for tumors with a tumor proportion score (TPS) ≥ 50%. This noninterventional, retrospective, multicenter study, conducted with the GFPC, included treatment-naïve patients strongly positive for PD-L1 (TPS ≥ 50%) with BM receiving first-line single-agent pembrolizumab treatment between May 2017 and November 2019. The primary endpoints were centrally reviewed intracranial overall response rates (ORRs), centrally reviewed intracranial progression-free survival (cPFS), extracranial PFS, and overall survival were secondary endpoints. Forty-three patients from five centers were included. Surgical or local radiation therapy was administered to 31 (72%) patients, mostly before initiating ICI therapy (25/31). Among 38/43 (88.4%) evaluable patients, the intracranial ORR was 73%. The median PFS was 8.3 months. The cerebral and extracerebral median PFS times were 9.2 and 5.3 months, respectively. The median OS was 25.5 months. According to multivariate analysis, BM surgery before ICI therapy was the only factor significantly associated with both improved PFS (HR = 0.44) and OS (HR = 0.45). This study revealed the feasibility and outcome of front-line pembrolizumab treatment in this population with BM.

Breast cancer is the most common cancer diagnosed in women and is often treated with chemotherapy. Although previous studies have demonstrated increasing biological age in patients who receive chemotherapy, evaluation of this association with DNA methylation-based markers of biological ageing may provide novel insight into the role of chemotherapy on the ageing process. We therefore sought to investigate the association between chemotherapy and markers of biological ageing as estimated from DNA methylation in women with breast cancer. DNA methylation profiling was performed on peripheral blood collected from 18 patients before and after the first cycle of chemotherapy using the Infinium HumanMethylation450 BeadChip. Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. After adjusting for chronological age and race, intrinsic epigenetic age acceleration (p = 0.041), extrinsic epigenetic age acceleration (p = 0.050), PhenoAge acceleration (p = 0.001), GrimAge acceleration (p

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (n = 1,030) and 20 (n = 945) were included. Liquor and total alcohol consumption were associated with a 0.31-year (P = 0.002) and a 0.12-year (P = 0.013) greater GrimAge acceleration (GAA) per additional five alcohol years, while beer and wine consumption observed marginal (P = 0.075) and no associations (P = 0.359) with GAA, respectively. Any recent binge drinking and the number of days of binge drinking were associated with a 1.38-year (P < 0.001) and a 0.15-year (P < 0.001) higher GAA, respectively. We observed statistical interactions between cumulative beer (P < 0.001) and total alcohol (P = 0.004) consumption with chronological age, with younger participants exhibiting a higher average in GAA compared to older participants. No associations were observed with the other measures of epigenetic aging. These results suggest cumulative liquor and total alcohol consumption and recent binge drinking may alter age-related epigenetic changes as captured by GAA. With the increasing aging population and widespread consumption of alcohol, these findings may have potential implications for lifestyle modification to promote healthy aging.

BackgroundMarijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana's effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.ResultsA random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P

The experimental setup GAMIPE used for gyro magnetic factor measurements at Laboratori Nazionali di Legnaro and a recent experimental work regarding K-isomers in 174W are described. Aim of the experiment is to study the detailed structure of the isomeric states wave functions, by the measurement of the magnetic dipole moments. This piece of information can provide interesting hints for theoretical models. Preliminary results concerning the population of the isomers of interest and half-lives are presented.

Coronary computed tomography angiography (CCTA) allows detailed assessment of early markers associated with coronary artery disease (CAD), such as coronary artery calcium (CAC) and tortuosity (CorT). However, their analysis can be time-demanding and biased. We present a fully automated pipeline that performs (i) coronary artery segmentation and (ii) CAC and CorT objective analysis. Our method exploits supervised learning for the segmentation of the lumen, and then, CAC and CorT are automatically quantified. 281 manually annotated CCTA images were used to train a two-stage U-Net-based architecture. The first stage employed a 2.5D U-Net trained on axial, coronal, and sagittal slices for preliminary segmentation, while the second stage utilized a multichannel 3D U-Net for refinement. Then, a geometric post-processing was implemented: vessel centerlines were extracted, and tortuosity score was quantified as the count of branches with three or more bends with change in direction forming an angle >45°. CAC scoring relied on image attenuation. CAC was detected by setting a patient specific threshold, then a region growing algorithm was applied for refinement. The application of the complete pipeline required

The ability of a cluster of three segmented Ge crystals (“AGATA module”) acting as a Compton polarimeter to measure the linear polarization of gamma rays has been investigated at an energy close to 511 keV. Partially polarized gamma rays have been produced by Coulomb excitation of the first excited state of 104Pd a and 108Pd.

The 48Ti on 40Ca reactions have been studied at 300 and 600 MeV focusing on the fusion-evaporation (FE) and fusion-fission (FF) exit channels. Energy spectra and multiplicities of the emitted light charged particles have been compared to Monte Carlo simulations based on the statistical model. Indeed, in this mass region (A ~ 100) models predict that shape transitions can occur at high spin values and relatively scarce data exist in the literature about coincidence measurements between evaporation residues and light charged particles. Signals of shape transitions can be found in the variations of the lineshape of high energy gamma rays emitted from the de-excitation of GDR states gated on different region of angular momenta. For this purpose it is important to keep under control the FE and FF processes, to regulate the statistical model parameters and to control the onset of possible pre-equilibrium emissions from 300 to 600 MeV bombarding energy.