Search

Aims/hypothesis: A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA). Methods: We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events. Results: Model development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications. Conclusions/interpretation: Precision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries. [ABSTRACT FROM AUTHOR]

Globally, there is a concerning decline in many insect populations, and this trend likely extends to all arthropods, potentially impacting unique island biota. Native non-endemic and endemic species on islands are under threat due to habitat destruction, with the introduction of exotic, and potentially invasive, species, further contributing to this decline. While long-term studies of plants and vertebrate fauna are available, long-term arthropod datasets are limited, hindering comparisons with better-studied taxa. The Biodiversity of Arthropods of the Laurisilva of the Azores (BALA) project has allowed gathering comprehensive data since 1997 in the Azorean Islands (Portugal), using standardised sampling methods across islands. The dataset includes arthropod counts from epigean (pitfall traps) and canopy-dwelling (beating samples) communities, enriched with species information, biogeographic origins, and IUCN categories. Metadata associated with the sample protocol and events, like sample identifier, archive number, sampled tree species, and trap type are also recorded. The database is available in multiple formats, including Darwin Core, which facilitates the ecological analysis of pressing environmental concerns, such as arthropod population declines and biological invasions. [ABSTRACT FROM AUTHOR]

Beneficial microorganisms for corals (BMCs), or probiotics, can enhance coral resilience against stressors in laboratory trials. However, the ability of probiotics to restructure the coral microbiome in situ is yet to be determined. As a first step to elucidate this, we inoculated putative probiotic bacteria (pBMCs) on healthy colonies of Pocillopora verrucosa in situ in the Red Sea, three times per week, during 3 months. pBMCs significantly influenced the coral microbiome, while bacteria of the surrounding seawater and sediment remained unchanged. The inoculated genera Halomonas, Pseudoalteromonas, and Bacillus were significantly enriched in probiotic-treated corals. Furthermore, the probiotic treatment also correlated with an increase in other beneficial groups (e.g., Ruegeria and Limosilactobacillus), and a decrease in potential coral pathogens, such as Vibrio. As all corals (treated and non-treated) remained healthy throughout the experiment, we could not track health improvements or protection against stress. Our data indicate that healthy, and therefore stable, coral microbiomes can be restructured in situ, although repeated and continuous inoculations may be required in these cases. Further, our study provides supporting evidence that, at the studied scale, pBMCs have no detectable off-target effects on the surrounding microbiomes of seawater and sediment near inoculated corals. Pioneering coral probiotics study shows in situ application reshapes the coral microbiome, boosting beneficial bacteria and reducing pathogens without affecting surrounding seawater and sediment microbiomes. [ABSTRACT FROM AUTHOR]