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Aim: To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants. Materials and methods: In SOUL, the effects of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double-blind, parallel-group, placebo-controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate

Dental calculus and other preserved microbiome substrates are an attractive target for dietary reconstruction in past populations through a variety of physical, chemical, and molecular means. Recently, studies have attempted to reconstruct diet from archaeological dental calculus using archaeogenetic techniques. While dental calculus may provide a relatively stable environment for DNA preservation, the detection of plants and animals possibly consumed by an individual through DNA analysis is primarily hindered by microbial richness and incomplete reference databases. Moreover, high genomic similarity within eukaryotic groups 1. Introduction 2. Materials and methods 3. Results 3.1. Effects of low read counts on damage patterns 3.2. Identification of dietary reads from synthetic datasets 3.3. Identification of dietary reads from real datasets 4. Discussion and conclusions 4.1. Checklist for authors and reviewers 4.1.1. Field/storage contamination 4.1.2. Is the laboratory methodology suitable for aDNA authentication? 4.1.3. Is the database and pipeline suitable? 4.1.4. Is the taxonomic resolution analyzed sufficient for reliable interpretation? 4.1.5. Have unexpected taxa been reported and evaluated? 4.1.6. Have laboratory controls been evaluated alongside samples? 4.1.7. Has evidence of aDNA authenticity been provided? 4.1.8. Is there other evidence supporting that dietary organisms were consumed?

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth’s energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth’s climate system. In 2022, the world’s oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0–2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the “salty gets saltier—fresh gets fresher” pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Hydrogen peroxide is an aerobic metabolite playing a central role in redox signaling and oxidative stress. H

To understand the presence of transient autophony symptoms in patients being treated for severe anorexia nervosa (AN), and whether those symptoms were due to patulous eustachian tube (PET).A prospective observational study was performed in patients requiring admission for treatment of severe AN. All enrolled patients completed The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and were screened for symptoms of autophony. If patients reported autophony and had a score of ≥14.5 on the ETDQ-7 they were asked to undergo comprehensive audiological testing and an evaluation with an otolaryngologist.Of the 73 patients enrolled in the study, 35 patients (44%) reported autophony and 36 (49%) scored 14.5 or higher on the ETDQ-7. Of the 16 (22%) patients who had both autophony and an ETDQ-7 score of 14.5 or higher, 7 patient s (representing 11 symptomatic ears) underwent evaluations by audiology and otolaryngology. Every evaluation of a symptomatic ear revealed objective evidence of PET. Nine of 11 (81.8%) symptomatic ears had subjectively resolved within 12 days of admission after nutritional rehabilitation and weight gain.Transient autophony in severe AN patients is due to PET, and was present in at least 8% of patients within our cohort. Further study is warranted to understand the quality of life impact and pathophysiology of transient PET in this patient population.

High-amplitude quasi-stationary atmospheric Rossby waves with zonal wave numbers 6 to 8 associated with the phenomenon of quasi-resonant amplification (QRA) have been linked to persistent summer extreme weather events in the Northern Hemisphere. We project future occurrence of QRA events based on an index derived from the zonally averaged surface temperature field, comparing results from CMIP5 and CMIP6 (Coupled Model Intercomparison Projects) climate projections. Under the scenarios analyzed, there is a general agreement among models, with most simulations projecting a substantial increase in QRA index. Larger increases are found among CMIP6-SSP585 (42 models, 46 realizations) models with 85% of models displaying a positive trend, as compared with as compared with 60% of CMIP5-RCP85 (35 models, 75 realizations), and a reduced spread among SSP585 models. The CMIP6-SSP370 (24 models, 28 realizations) simulations display qualitatively similar behavior to SSP585, indicating a substantial increase in QRA events under business-as-usual emissions scenarios. Our analysis suggests that anthropogenic warming will likely lead to an even more substantial increase in QRA events (and associated summer weather extremes) than our previous analysis of CMIP5 simulations.

Lipid metabolism and signalling play pivotal functions in biology and disease development. Despite this, there is currently no optical technique available that can directly visualise the lipidome in tissues. In this study, we introduce opto-lipidomics, a new approach to optical molecular tissue imaging. We expand the capability of vibrational Raman spectroscopy to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionisation (DESI) - mass spectrometry imaging in an integrated instrument. A computational pipeline of inter-modality regression analysis is established to extract lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualisation and identification of lipids in disease with unprecedented molecular specificity using light. Furthermore, we deploy opto-lipidomics in a handheld fiber-optic Raman probe and demonstrate real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.

The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year’s record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.

BackgroundChronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and lower body weight in people with T2D, and some reduce the risk of cardiovascular (CV) events in those with high CV risk. GLP-1RAs might also have kidney-protective effects. We report the design and baseline data for FLOW (NCT03819153), a trial investigating the effects of semaglutide, a once-weekly (OW) GLP-1RA, on kidney outcomes in participants with CKD and T2D.MethodsFLOW is a randomised, double-blind, parallel-group, multinational, phase 3b trial. Participants with T2D, estimated glomerular filtration rate (eGFR) ≥50‒≤75 ml/min/1.73 m2 and urine albumin:creatinine ratio (UACR) >300‒100‒ResultsEnrolled participants (N = 3534) had a baseline mean age of 66.6 years [standard deviation (SD) 9.0], haemoglobin A1c of 7.8% (SD 1.3), diabetes duration of 17.4 years (SD 9.3), eGFR of 47.0 ml/min/1.73 m2 (SD 15.2) and median UACR of 568 mg/g (range 2‒11 852). According to Kidney Disease: Improving Global Outcomes guidelines categorisation, 68.2% were at very high risk for CKD progression.ConclusionFLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to be completed in late 2024.