Four targets: an enhanced framework for guiding causal inference from observational data.

Observational studies play an increasingly important role in estimating causal effects of a treatment or an exposure, especially with the growing availability of routinely collected real-world data. To facilitate drawing causal inference from observational data, we introduce a conceptual framework centered around "four targets"-target estimand, target population, target trial, and target validity. We illustrate the utility of our proposed "four targets" framework with the example of buprenorphine dosing for treating opioid use disorder, explaining the rationale and process for employing the framework to guide causal thinking from observational data.

Analysis of Pz-1, a promising therapeutic for organophosphorus poisoning from rodent plasma by liquid chromatography-tandem mass spectrometry.

Organophosphorus (OP) pesticides (e.g., parathion) and nerve agents (e.

The relationship of medical and recreational cannabis laws with opioid misuse and opioid use disorder in the USA: Does it depend on prior history of cannabis use?

Background: Wider availability of cannabis through medical and recreational legalization (MCL alone and RCL+MCL) has been hypothesized to contribute to reductions in opioid use, misuse, and related harms. We examined whether state adoption of cannabis laws was associated with changes in opioid outcomes overall and stratified by cannabis use.

Methods: Using National Survey on Drug Use and Health (NSDUH) data from 2015 to 2019, we estimated cannabis law associations with opioid (prescription opioid misuse and/or heroin use) misuse and use disorder.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.