Cheminformatics and artificial intelligence for accelerating agrochemical discovery.

The global cost-benefit analysis of pesticide use during the last 30 years has been characterized by a significant increase during the period from 1990 to 2007 followed by a decline. This observation can be attributed to several factors including, but not limited to, pest resistance, lack of novelty with respect to modes of action or classes of chemistry, and regulatory action. Due to current and projected increases of the global population, it is evident that the demand for food, and consequently, the usage of pesticides to improve yields will increase. Addressing these challenges and needs while promoting new crop protection agents through an increasingly stringent regulatory landscape requires the development and integration of infrastructures for innovative, cost- and time-effective discovery and development of novel and sustainable molecules. Significant advances in artificial intelligence (AI) and cheminformatics over the last two decades have improved the decision-making power of research scientists in the discovery of bioactive molecules. AI- and cheminformatics-driven molecule discovery offers the opportunity of moving experiments from the greenhouse to a virtual environment where thousands to billions of molecules can be investigated at a rapid pace, providing unbiased hypothesis for lead generation, optimization, and effective suggestions for compound synthesis and testing. To date, this is illustrated to a far lesser extent in the publicly available agrochemical research literature compared to drug discovery. In this review, we provide an overview of the crop protection discovery pipeline and how traditional, cheminformatics, and AI technologies can help to address the needs and challenges of agrochemical discovery towards rapidly developing novel and more sustainable products.

Practice patterns in the conservative treatment of carpal tunnel syndrome: Survey results from members of the American Society of Hand Therapy.

STUDY DESIGN: A cross-sectional descriptive design was used. INTRODUCTION: Carpal tunnel syndrome (CTS) is a complex combination of symptoms resulting from compression of the median nerve within the carpal tunnel. A study that compares the conservative interventions identified in the literature with the actual conservative interventions being implemented by therapists for the treatment of CTS is not presently available. PURPOSE OF THE STUDY: The purpose of this study was to examine conservative interventions for CTS as reported by certified hand therapists (CHTs) within various clinical settings. The study also aimed to identify the decision-making process for the selection of CTS interventions. METHOD: CHT members of the American Society of Hand Therapists were surveyed electronically to obtain quantitative data. RESULTS: Patient education, nocturnal orthosis, and ergonomic modifications ranked among the top conservative interventions utilized for CTS, whereas treatments such as magnet therapy, C-TRAC, and heating lamps ranked among the least utilized interventions. When selecting interventions, clinical expertise, research evidence, and patient preferences were all highly valued considerations for CHT. DISCUSSION: Our study offers a unique summary of CHT practice patterns for CTS interventions and the associated decision-making processes. It compares findings with existing literature on this topic, offering researchers and clinicians a glimpse of the CTS practice trends. CONCLUSION: This study may serve to prioritize future research studies based on the prevalence of intervention usage among the experts. It also serves as a guide to those seeking to understand the most common interventions utilized for conservative CTS treatment.

Levuglandinyl adducts of proteins are formed via a prostaglandin H2 synthase-dependent pathway after platelet activation.

The product of oxygenation of arachidonic acid by the prostaglandin H synthases (PGHS), prostaglandin H(2) (PGH(2)), undergoes rearrangement to the highly reactive gamma-ketoaldehydes, levuglandin (LG) E(2), and LGD(2). We have demonstrated previously that LGE(2) reacts with the epsilon-amine of lysine to form both the levuglandinyl-lysine Schiff base and the pyrrole-derived levuglandinyl-lysine lactam adducts. We also have reported that these levuglandinyl-lysine adducts are formed on purified PGHSs following the oxygenation of arachidonic acid. We now present evidence that the levuglandinyl-lysine lactam adduct is formed in human platelets upon activation with exogenous arachidonic acid or thrombin. After proteolytic digestion of the platelet proteins, and isolation of the adducted amino acid residues, this adduct was identified by liquid chromatography-tandem mass spectrometry. We also demonstrate that formation of these adducts is inhibited by indomethacin, a PGHS inhibitor, and is enhanced by an inhibitor of thromboxane synthase. These data establish that levuglandinyl-lysine adducts are formed via a PGHS-dependent pathway in whole cells, even in the presence of an enzyme that metabolizes PGH(2). They also demonstrate that a physiological stimulus is sufficient to lead to the lipid modification of proteins through the levuglandin pathway in human platelets.