The influential IPr: 25 years after its discovery.

N-Heterocyclic carbenes (NHCs) have emerged as a privileged ligand family in organometallic chemistry, widely recognized for their unique steric and electronic properties. Among them, the 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene (IPr) ligand has become a cornerstone of NHC chemistry for its remarkable versatility, stability, and broad use. Since its discovery by the Nolan group in 1999, IPr has played a pivotal role in advancing catalytic transformations and facilitating the utilization of NHC ligands in various domains.

A highly conserved sRNA downregulates multiple genes, including a σ transcriptional activator, in the virulence mode of .

Bacterial sRNAs together with the RNA chaperone Hfq post-transcriptionally regulate gene expression by affecting ribosome binding or mRNA stability. In the human pathogen , the causative agent of whooping cough, hundreds of sRNAs have been identified, but their roles in biology are mostly unknown. Here we characterize a Hfq-dependent sRNA (S17), whose level is dramatically higher in the virulence (Bvg) mode.

Recurrent activity propagates through labile ensembles in macaque dorsolateral prefrontal microcircuits.

Human and non-human primate studies clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions. It is thought that intracortical synaptic architectures within the dlPFC are the integral neurobiological substrate that gives rise to these processes. In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the "canonical" cortical microcircuit.

[Cu(NHC)(OR)] (R = C(CF)) complexes for N-H and S-H bond activation and as pre-catalysts in the Chan-Evans-Lam reaction.

The synthesis, isolation, and full characterization of a series of NHC-copper perfluoro-alkoxide complexes are reported. Their exceptional stability resides with the steric hindrance of the nonafluoro--butyl alkoxide moiety, which exhibits a strong electron withdrawing effect. These new Cu(I) complexes are synthons that can permit the activation of acidic N-H and S-H bonds.

Simple synthesis of [Au(NHC)X] complexes utilizing aqueous ammonia: revisiting the mechanism.

Aqueous ammonia has been examined as a new weak base for the synthesis of [Au(NHC)Cl] complexes, as well as for the activation of C-H, S-H, and N-H bonds. Its low cost and mild operational conditions (in air and using technical grade solvents) make it an attractive alternative for producing gold-NHC complexes. Synthetic pathways have been investigated , assessing the role of the deprotonation and metalation steps within the reaction mechanisms.

Gold-catalyzed hydrofluorination of terminal alkynes using potassium bifluoride (KHF).

A gold-catalyzed hydrofluorination of terminal alkynes is reported. The salient features of this study showcase the use of potassium bifluoride, KHF, as the fluorinating agent in conjunction with a fluorinated solvent, hexafluoroisopropanol. The reaction is mediated by a well-defined precursor, [Au(IPr)(OH)] with an acid activator.

Gold-Mediated Cyclization of -Acrylamides via Energy Transfer Photocatalysis.

We disclose a gold-mediated photocyclization method for the efficient synthesis of acrylamide-derived β-lactams and 3,4-dihydroquinolin-2-ones, two privileged bioactive scaffolds. The protocol proceeds with ease, providing good yields of product while exhibiting excellent functional group tolerance at low catalyst loadings in sustainable solvents. Additionally, reaction times are significantly reduced compared with prior-art methods.

Development and in-vitro assessment of novel oxygen-releasing feed additives to reduce enteric ruminant methane emissions.

Ruminant livestock contribute significantly to global methane production and mitigation of which is of utmost importance. Feed additives represent a cost-effective means of achieving this. A potential target for such additives is rumen Oxidative Reduction Potential (ORP), a parameter which influences CH production rates, with methanogenesis occurring optimally at ORPs below -300 mV.

Machine learning directed discovery and optimisation of a platinum-catalysed amide reduction.

The discovery and optimisation of reaction conditions leading to the reduction of amides, a fundamental large-scale industrial reaction, is achieved using a machine learning (ML) platform and a platinum catalyst. The optimisation leads to the discovery of a new platinum-based catalytic system that displays unexpectedly high performance. The approach enables rapid and high conversions at ppm-level catalyst loadings.

The role of the stabilizing/leaving group in palladium catalysed cross-coupling reactions.

Despite the widespread use of well-defined Pd complexes as pre-catalysts for cross-coupling processes, the role of the throw-away ligand is still underexplored. In this work we focused on the complexes of the type [Pd(NHC)(η-R-allyl)Cl] (NHC = N-heterocyclic carbene) and we investigated the influence of the R substitution on the allyl moiety. Starting from the already described [Pd(IPr)(η-cinnamyl)Cl] and [Pd(IPr*)(η-cinnamyl)Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IPr* = ,'-1,3-bis[2,6-bis(diphenylmethyl)-4-methylphenyl]imidazol-2-ylidene) we prepared eight new complexes bearing new substitutions on the cinnamyl motif and we tested them in the C-N bond formation to evaluate the effect of the throw-away ligand modification in the catalytic activity.

Road to Recovery: protocol for a mixed-methods prospective cohort study evaluating the impact of a new model of substance use care in a Canadian setting.

Introduction: The Road to Recovery (R2R) Initiative is an innovative model of substance use care that seeks to increase treatment capacity by creating approximately 100 new addiction treatment beds to provide on-demand addiction care in Vancouver, British Columbia, for patients with substance use disorders. The new model also coordinates the region's existing clinical substance use services to support patients across a care continuum that includes traditional office-based addiction treatment and harm reduction services, early withdrawal management and more intensive abstinence-based treatment programming. To understand the impact of offering on-demand and coordinated substance use care, an observational cohort of individuals who access any R2R clinical service will be created to examine health and social outcomes over time.

Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue.

Nurse-led web-based self-management program to improve patient activation and health outcomes in patients with chronic low back pain: an acceptability and feasibility pilot study.

Background: Patients with chronic low back (cLBP) pain report reduced physical function and ability to participate in social roles and are more likely to use opioid pain medications. While self-management interventions have been shown to support these patients, their effectiveness has been limited due to poor patient engagement. "Patient activation" encompasses the skills, knowledge, and motivation that a person has to manage their health.

Projecting the clinical burden of chronic kidney disease at the patient level (): a microsimulation modelling study.

Background: Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. is an international initiative that aims to raise awareness of the substantial burden incurred by CKD.

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

Introduction: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992).

Methods: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision.

Synthesis and reactivity of N-heterocyclic carbene (NHC) gold-fluoroalkoxide complexes.

We disclose a novel series of N-heterocyclic carbene (NHC) gold complexes with varied steric and electronic properties, bearing fluorinated alkoxide anions. Early reactivity studies involving these synthons, lead to the synthesis of various complexes of relevance to gold chemistry and catalysis.

Synthesis of N-heterocyclic carbene (NHC)-Au/Ag/Cu benzotriazolyl complexes and their catalytic activity in propargylamide cycloisomerization and carbonyl hydrosilylation reactions.

Carbene-metal-amide (CMA) complexes of gold, silver, and copper have been studied extensively for their photochemical/photocatalytic properties and as potential (pre-)catalysts in organic synthesis. Herein, the design, synthesis, and characterization of five bench-stable Au-, Ag-, and Cu-NHC complexes bearing the benzotriazolyl anion as an amide donor, are reported. All complexes are synthesized in a facile and straightforward manner, using mild conditions.

Urate-lowering therapy in patients with hyperuricemia and heart failure: A retrospective cohort study using the UK Clinical Practice Research Datalink.

Background: Elevated serum uric acid (sUA) is associated with heart failure (HF).

Hypothesis: Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality.

Methods: Data on patients with HF and gout or hyperuricemia in the Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and the Office for National Statistics in the United Kingdom were analyzed.

Characterising individuals with a substance use disorder accessing hospital-based addiction care: Preliminary description of the outcomes for patients accessing addiction care prospective cohort study.

Introduction: Individuals with a substance use disorder (SUD) often face barriers to accessing health care, resulting in unmet needs and delayed care. Hospital-based services have the potential to engage individuals with a SUD in ongoing treatment, but there is limited literature characterising this population.

Methods: The Outcomes for Patients Accessing Addiction Care study was a prospective hospital-based cohort study conducted at St.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative.