Closed-loop transfer enables artificial intelligence to yield chemical knowledge.

Artificial intelligence-guided closed-loop experimentation has emerged as a promising method for optimization of objective functions, but the substantial potential of this traditionally black-box approach to uncovering new chemical knowledge has remained largely untapped. Here we report the integration of closed-loop experiments with physics-based feature selection and supervised learning, denoted as closed-loop transfer (CLT), to yield chemical insights in parallel with optimization of objective functions. CLT was used to examine the factors dictating the photostability in solution of light-harvesting donor-acceptor molecules used in a variety of organic electronics applications, and showed fundamental insights including the importance of high-energy regions of the triplet state manifold.

A Modular Communicative Leadless Pacing-Defibrillator System.

Background: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown.

Methods: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system.

Delocalized, asynchronous, closed-loop discovery of organic laser emitters.

Contemporary materials discovery requires intricate sequences of synthesis, formulation, and characterization that often span multiple locations with specialized expertise or instrumentation. To accelerate these workflows, we present a cloud-based strategy that enabled delocalized and asynchronous design-make-test-analyze cycles. We showcased this approach through the exploration of molecular gain materials for organic solid-state lasers as a frontier application in molecular optoelectronics.

Minimizing higher-order aggregation maximizes iron mobilization by small molecules.

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization.

Predictive value of the PRAETORIAN score for defibrillation test success in patients with subcutaneous ICD: A subanalysis of the PRAETORIAN-DFT trial.

Background: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events.

Objective: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias.

Computational prediction of complex cationic rearrangement outcomes.

Recent years have seen revived interest in computer-assisted organic synthesis. The use of reaction- and neural-network algorithms that can plan multistep synthetic pathways have revolutionized this field, including examples leading to advanced natural products. Such methods typically operate on full, literature-derived 'substrate(s)-to-product' reaction rules and cannot be easily extended to the analysis of reaction mechanisms.

Impact of Age on Subcutaneous Implantable Cardioverter-Defibrillator in a Large Patient Cohort: Mid-Term Follow-Up.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an accepted alternative to transvenous (TV) ICD to provide defibrillation therapy to treat life-threatening ventricular tachyarrhythmias in high-risk patients. S-ICD outcomes by age group have not been reported.

Objectives: In this study, the authors sought to report S-ICD outcomes in different age groups in a multicenter S-ICD post-approval study (PAS) involving the largest cohort of patients ever reported.

Initial Experience With Intercostal Insertion of an Extravascular ICD Lead Compatible With Existing Pulse Generators.

Background: This study assessed safety and feasibility of a novel extravascular implantable cardioverter defibrillator (ICD) lead when inserted anteriorly through a rib space and connected to various commercially available ICD pulse generators (PGs) placed in either a left mid-axillary or left pectoral pocket. Currently available or investigational, extravascular-ICDs include a subcutaneous or subxiphoid lead connected to customized extravascular-ICD PGs.

Methods: This novel extravascular-ICD (AtaCor Medical Inc, San Clemente, CA) employs a unique intercostal implant technique and is designed to function with commercial DF-4 ICD PGs.

MIDA- and TIDA-Boronates Stabilize α-Radicals Through B-N Hyperconjugation.

Multifunctional organoboron compounds increasingly enable the simple generation of complex, Csp -rich small molecules. The ability of boron-containing functional groups to modify the reactivity of α-radicals has also enabled a myriad of chemical reactions. Boronic esters with vacant p-orbitals have a significant stabilizing effect on α-radicals due to delocalization of spin density into the empty orbital.

Design and rationale of the MODULAR ATP global clinical trial: A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support.

Objective: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented.

Postapproval Study of a Subcutaneous Implantable Cardioverter-Defibrillator System.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) was developed to avoid complications related to transvenous implantable cardioverter-defibrillator (TV-ICD) leads. Device safety and efficacy were demonstrated previously with atypical clinical patients or limited follow-up.

Objectives: The S-ICD PAS (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study) is a real-world, multicenter, registry of U.

Intraoperative Neurophysiological Monitoring During Lead Placement for Dorsal Root Ganglion Stimulation: A Literature Review and Case Series.

Introduction: Dorsal root ganglion stimulation (DRG-S) is a viable interventional option for intractable pain management. Although systematic data are lacking regarding the immediate neurologic complications of this procedure, intraoperative neurophysiological monitoring (IONM) can be a valuable tool to detect real-time neurologic changes and prompt intervention(s) during DRG-S performed under general anesthesia and deep sedation.

Materials And Methods: In our single-center case series, we performed multimodal IONM, including peripheral nerve somatosensory evoked potentials (pnSSEPs) and dermatomal somatosensory evoked potentials (dSSEPs), spontaneous electromyography (EMG), transcranial motor evoked potentials (MEPs), and electroencephalogram (EEG) for some trials and all permanent DRG-S lead placement per surgeon preference.

A Materials Acceleration Platform for Organic Laser Discovery.

Conventional materials discovery is a laborious and time-consuming process that can take decades from initial conception of the material to commercialization. Recent developments in materials acceleration platforms promise to accelerate materials discovery using automation of experiments coupled with machine learning. However, most of the automation efforts in chemistry focus on synthesis and compound identification, with integrated target property characterization receiving less attention.

Closed-loop optimization of general reaction conditions for heteroaryl Suzuki-Miyaura coupling.

General conditions for organic reactions are important but rare, and efforts to identify them usually consider only narrow regions of chemical space. Discovering more general reaction conditions requires considering vast regions of chemical space derived from a large matrix of substrates crossed with a high-dimensional matrix of reaction conditions, rendering exhaustive experimentation impractical. Here, we report a simple closed-loop workflow that leverages data-guided matrix down-selection, uncertainty-minimizing machine learning, and robotic experimentation to discover general reaction conditions.

Outcomes and challenges of the provisional stenting technique: Insights from the PROGRESS-BIFURCATION registry.

Background: Provisional stenting is the most commonly used coronary bifurcation stenting strategy.

Methods: We examined the clinical and angiographic characteristics, challenges encountered, and procedural outcomes with the provisional bifurcation stenting strategy in the Prospective Global Registry of Percutaneous Coronary Intervention (PCI) in Bifurcation Lesions (PROGRESS-BIFURCATION, NCT05100992).

Results: Provisional stenting was used in 334 of 430 bifurcation interventions (78%).

FAIR data pipeline: provenance-driven data management for traceable scientific workflows.

Modern epidemiological analyses to understand and combat the spread of disease depend critically on access to, and use of, data. Rapidly evolving data, such as data streams changing during a disease outbreak, are particularly challenging. Data management is further complicated by data being imprecisely identified when used.

Infection in patients with subcutaneous implantable cardioverter-defibrillator: Results of the S-ICD Post Approval Study.

Background: Early subcutaneous implantable cardioverter-defibrillator (S-ICD) studies included atypical cohorts of patients who were younger with fewer comorbidities. Recent S-ICD studies included patient populations with more comorbidities.

Objectives: The goals of this study were to determine the incidence and predictors of S-ICD-related infection over a 3-year follow-up period and to use these results to develop an infection risk score.

Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation.

Fungal infections cause more than 1.5 million deaths annually. With an increase in immune-deficient susceptible populations and the emergence of antifungal drug resistance, there is an urgent need for novel strategies to combat these life-threatening infections.

A small molecule redistributes iron in ferroportin-deficient mice and patient-derived primary macrophages.

Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause the iron misdistribution that underlies ferroportin disease, anemia of inflammation, and several other human diseases and conditions. A small molecule natural product, hinokitiol, was recently shown to serve as a surrogate transmembrane iron transporter that can restore hemoglobinization in zebrafish deficient in other iron transporting proteins and can increase gut iron absorption in FPN1-deficient flatiron mice. However, whether hinokitiol can restore normal iron physiology in FPN1-deficient animals or primary cells from patients and the mechanisms underlying such targeted activities remain unknown.