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The restrictive measures implemented to stem the spread of COVID-19 abruptly changed the lives of many cats and their owners. This study explored whether the lockdown in Italy affected the cat–owner relationship, as well as cat behaviour and welfare. A survey that included questions on owner and cat’s demographics, living environment, cat behaviour and a modified version of the Cat/Dog Relationship Scale (C/DORS) was distributed online during the lockdown and was completed by 548 cat owners, mainly women (81.6%). With regard to the C/DORS subscales, both emotional closeness and cat–owner interactions increased during confinement, as opposed to a reduction in perceived costs. The effect of the type of job, family role and owner’s age on the C/DORS scores suggests that the relationship improved for those owners that, due to the lockdown, increased the time spent with their cats. For 58.8% of respondents, their cat’s general behaviour did not change, but when changes occurred, they were mostly positive (20.4%). Attention-seeking and demanding behaviours were the most increased during lockdown (25.7%). Cats with pre-existing problematic behaviours tended to either remain stable or improve during confinement. The overall positive effects of lockdown-related environmental changes on a cat’s behaviour suggest that some aspects of commonly implemented cat management practices should be revised to improve cat welfare in normal circumstances.

Tezepelumab is a monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell–derived cytokine implicated in the pathogenesis of asthma. This randomized, placebo-controlled clinical trial showed a reduction in the annualized rate of asthma exacerbations among patients with severe, uncontrolled asthma treated with tezepelumab.

The Omicron variant of SARS‐CoV‐2 achieved worldwide dominance in late 2021. Early work suggests that infections caused by the Omicron variant may be less severe than those caused by the Delta variant. We sought to compare clinical outcomes of infections caused by these two strains, confirmed by whole genome sequencing, over a short period of time, from respiratory samples collected from SARS‐CoV‐2 positive patients at a large medical center. We found that infections caused by the Omicron variant caused significantly less morbidity, including admission to the hospital and requirement for oxygen supplementation, and significantly less mortality than those caused by the Delta variant.

Acute promyelocytic leukaemia is a chemotherapy-sensitive subgroup of acute myeloid leukaemia characterised by the presence of the PML–RARA fusion transcript. The present standard of care, chemotherapy and all-trans retinoic acid (ATRA), results in a high proportion of patients being cured. In this study, we compare a chemotherapy-free ATRA and arsenic trioxide treatment regimen with the standard chemotherapy-based regimen (ATRA and idarubicin) in both high-risk and low-risk patients with acute promyelocytic leukaemia. In the randomised, controlled, multicentre, AML17 trial, eligible patients (aged ≥16 years) with acute promyelocytic leukaemia, confirmed by the presence of the PML–RARA transcript and without significant cardiac or pulmonary comorbidities or active malignancy, and who were not pregnant or breastfeeding, were enrolled from 81 UK hospitals and randomised 1:1 to receive treatment with ATRA and arsenic trioxide or ATRA and idarubicin. ATRA was given to participants in both groups in a daily divided oral dose of 45 mg/m2 until remission, or until day 60, and then in a 2 weeks on–2 weeks off schedule. In the ATRA and idarubicin group, idarubicin was given intravenously at 12 mg/m2 on days 2, 4, 6, and 8 of course 1, and then at 5 mg/m2 on days 1–4 of course 2; mitoxantrone at 10 mg/m2 on days 1–4 of course 3, and idarubicin at 12 mg/m2 on day 1 of the final (fourth) course. In the ATRA and arsenic trioxide group, arsenic trioxide was given intravenously at 0·3 mg/kg on days 1–5 of each course, and at 0·25 mg/kg twice weekly in weeks 2–8 of course 1 and weeks 2–4 of courses 2–5. High-risk patients (those presenting with a white blood cell count >10 × 109 cells per L) could receive an initial dose of the immunoconjugate gemtuzumab ozogamicin (6 mg/m2 intravenously). Neither maintenance treatment nor CNS prophylaxis was given to patients in either group. All patients were monitored by real-time quantitative PCR. Allocation was by central computer minimisation, stratified by age, performance status, and de-novo versus secondary disease. The primary endpoint was quality of life on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status. All analyses are by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN55675535. Between May 8, 2009, and Oct 3, 2013, 235 patients were enrolled and randomly assigned to ATRA and idarubicin (n=119) or ATRA and arsenic trioxide (n=116). Participants had a median age of 47 years (range 16–77; IQR 33–58) and included 57 high-risk patients. Quality of life did not differ significantly between the treatment groups (EORTC QLQ-C30 global functioning effect size 2·17 [95% CI −2·79 to 7·12; p=0·39]). Overall, 57 patients in the ATRA and idarubicin group and 40 patients in the ATRA and arsenic trioxide group reported grade 3–4 toxicities. After course 1 of treatment, grade 3–4 alopecia was reported in 23 (23%) of 98 patients in the ATRA and idarubicin group versus 5 (5%) of 95 in the ATRA and arsenic trioxide group, raised liver alanine transaminase in 11 (10%) of 108 versus 27 (25%) of 109, oral toxicity in 22 (19%) of 115 versus one (1%) of 109. After course 2 of treatment, grade 3–4 alopecia was reported in 25 (28%) of 89 patients in the ATRA and idarubicin group versus 2 (3%) of 77 in the ATRA and arsenic trioxide group; no other toxicities reached the 10% level. Patients in the ATRA and arsenic trioxide group had significantly less requirement for most aspects of supportive care than did those in the ATRA and idarubicin group. ATRA and arsenic trioxide is a feasible treatment in low-risk and high-risk patients with acute promyelocytic leukaemia, with a high cure rate and less relapse than, and survival not different to, ATRA and idarubicin, with a low incidence of liver toxicity. However, no improvement in quality of life was seen. Cancer Research UK.

Identifying metabolic biomarkers of frailty, an age‐related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance‐based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two‐sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (β per SD increase = 0.37%, 95% confidence interval: 0.12–0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development. This study explored the relationships between frailty and circulating metabolic biomarkers measured using a standardized nuclear magnetic resonance (NMR) metabolomics platform in three large European population‐based studies. Out of the 200 assessed biomarkers, 34 were found to be robustly associated with frailty in the observational analysis. Two‐sample Mendelian randomization further implicated potential causal relationships of glycoprotein acetyls, creatinine, and several lipoprotein lipids with frailty.

Background Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm 3 , and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count – focusing on blood EOS count 100 to < 300 cells/mm 3 – as a function of exacerbation history and COPD severity. Methods In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV 1 ) over 12–24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. Results Among patients with blood EOS count 100 to < 300 cells/mm 3 , least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. Conclusions These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm 3 , even if disease severity is moderate and there is no recent history of exacerbations. Trial registration ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).

Stable isotope data have made pivotal contributions to nearly every discipline of the physical and natural sciences. As the generation and application of stable isotope data continues to grow exponentially, so does the need for a unifying data repository to improve accessibility and promote collaborative engagement. This paper provides an overview of the design, development, and implementation of IsoBank ( www.isobank.org ), a community-driven initiative to create an open-access repository for stable isotope data implemented online in 2021. A central goal of IsoBank is to provide a web-accessible database supporting interdisciplinary stable isotope research and educational opportunities. To achieve this goal, we convened a multi-disciplinary group of over 40 analytical experts, stable isotope researchers, database managers, and web developers to collaboratively design the database. This paper outlines the main features of IsoBank and provides a focused description of the core metadata structure. We present plans for future database and tool development and engagement across the scientific community. These efforts will help facilitate interdisciplinary collaboration among the many users of stable isotopic data while also offering useful data resources and standardization of metadata reporting across eco-geoinformatics landscapes.

Stable isotopes encode and integrate the origin of matter; thus, their analysis offers tremendous potential to address questions across diverse scientific disciplines (1, 2). Indeed, the broad applicability of stable isotopes, coupled with advancements in high-throughput analysis, have created a scientific field that is growing exponentially, and generating data at a rate paralleling the explosive rise of DNA sequencing and genomics (3). Centralized data repositories, such as GenBank, have become increasingly important as a means for archiving information, and \"Big Data\" analytics of these resources are revolutionizing science and everyday life. However, to date a centralized database for the management of isotopic data does not exist. We believe that the absence of such a resource has impeded research progress through the unnecessary duplication of effort, restricted the near-boundless application of stable isotopes, and curtailed the exchange of information among researchers. The creation of such a centralized database would be more than a silo for data; it would be a dynamic resource to unite disciplinary fields and answer pressing questions in agriculture, animal sciences, archaeology, Anthropology, ecology, medicine, nutrition, physiology, paleontology, forensics, and earth and planetary sciences. We believe that a centralized database for isotopes would accelerate and enhance such global and multidisciplinary endeavors, thus broaden the reach of isotope science. Here, we-a group of stable isotope scientists, data managers, museum curators, journal editors, and educators-offer a vision for the public repository's identity, structure, and long-term sustainability.

We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β -agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited. KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV ) and FEV area under the curve from hours 0 to 4 (AUC ) change from baseline over 12-24 weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks with ICS/LAMA/LABA (BGF 320/14.4/10 µg), LAMA/LABA (glycopyrronium/formoterol fumarate dihydrate [GFF] 14.4/10 µg), and ICS/LABA (budesonide/formoterol fumarate dihydrate [BFF] 320/10 µg) in patients with phenotypic features of asthma defined as reversibility to salbutamol and blood eosinophils ≥300 cells/mm . Analyses were not adjusted for multiplicity. BGF improved trough FEV and FEV AUC versus GFF (least squares mean [LSM] difference [95% confidence interval (CI)] 125 [39-211] and 153 [59-247] mL) and BFF (LSM difference [95% CI] 118 [30-207] and 146 [49-243] mL). Exacerbation rates were estimated to be lower with BGF versus GFF and BFF (respective rate ratios [95% CI] 0.28 [0.19-0.43] and 0.69 [0.45-1.05]) and SGRQ total score was estimated to be improved with BGF versus GFF and BFF (respective LSM differences [95% CI] -5.18 [-8.11 to -2.24] and -1.09 [-4.08 to 1.91]). BGF was estimated to have benefits on lung function, exacerbations, and health-related quality of life versus dual therapies in patients with COPD and phenotypic features of asthma. ClinicalTrials.gov NCT02497001 and NCT02465567.

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.