Machine Learning Methods for Identifying Atrial Fibrillation Cases and Their Predictors in Patients With Hypertrophic Cardiomyopathy: The HCM-AF-Risk Model.

Background: Hypertrophic cardiomyopathy (HCM) patients have a high incidence of atrial fibrillation (AF) and increased stroke risk, even with low CHADS-VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack) scores. Hence, there is a need to understand the pathophysiology of AF/stroke in HCM. In this retrospective study, we develop and apply a data-driven, machine learning-based method to identify AF cases, and clinical/imaging features associated with AF, using electronic health record data.

Hydrogenation and electrocatalytic reduction of carbon dioxide to formate with a single Co catalyst.

A cobalt(i) complex is shown to be capable of both electrocatalytic reduction and hydrogenation of CO2 to formate. Several proposed intermediates are characterized and thus form the basis for a proposed mechanism that allows for the dual reactivity: reduction of CO2via H2 addition, and H+/e- equivalents. The work makes use of a novel tris(phosphino) ligand.

Toward Combined Carbon Capture and Recycling: Addition of an Amine Alters Product Selectivity from CO to Formic Acid in Manganese Catalyzed Reduction of CO.

Owing to the energetic cost associated with CO release in carbon capture (CC), the combination of carbon capture and recycling (CCR) is an emerging area of research. In this approach, "captured CO," typically generated by addition of amines, serves as a substrate for subsequent reduction. Herein, we report that the reduction of CO in the presence of morpholine (generating mixtures of the corresponding carbamate and carbamic acid) with a well-established Mn electrocatalyst changes the product selectivity from CO to H and formate.

The role of leached Zr in the photocatalytic reduction of CO to formate by derivatives of UiO-66 metal organic frameworks.

This work reports the photocatalytic reduction of CO2 to formate that is mediated by UiO-66 Zr MOF derivatives. Amino-substituted UiO-66 is a known photocatalyst for this transformation, and herein we identify that this catalysis is due to leached Zr, not the MOF itself. No correlation between catalytic activity and crystal size is observed for UiO-66-NH2.

Identifying Ventricular Arrhythmias and Their Predictors by Applying Machine Learning Methods to Electronic Health Records in Patients With Hypertrophic Cardiomyopathy (HCM-VAr-Risk Model).

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD.

Chronic Kidney Disease stratification using office visit records: Handling data imbalance via hierarchical meta-classification.

Background: Chronic Kidney Disease (CKD) is one of several conditions that affect a growing percentage of the US population; the disease is accompanied by multiple co-morbidities, and is hard to diagnose in-and-of itself. In its advanced forms it carries severe outcomes and can lead to death. It is thus important to detect the disease as early as possible, which can help devise effective intervention and treatment plan.

Co-occurrence of medical conditions: Exposing patterns through probabilistic topic modeling of snomed codes.

Patients associated with multiple co-occurring health conditions often face aggravated complications and less favorable outcomes. Co-occurring conditions are especially prevalent among individuals suffering from kidney disease, an increasingly widespread condition affecting 13% of the general population in the US. This study aims to identify and characterize patterns of co-occurring medical conditions in patients employing a probabilistic framework.

Modulation of curli assembly and pellicle biofilm formation by chemical and protein chaperones.

Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation.

Rational design of potent domain antibody inhibitors of amyloid fibril assembly.

Antibodies hold significant potential for inhibiting toxic protein aggregation associated with conformational disorders such as Alzheimer's and Huntington's diseases. However, near-stoichiometric antibody concentrations are typically required to completely inhibit protein aggregation. We posited that the molecular interactions mediating amyloid fibril formation could be harnessed to generate antibodies with potent antiaggregation.

Aggregation-resistant domain antibodies engineered with charged mutations near the edges of the complementarity-determining regions.

Antibodies commonly contain hydrophobic residues within their complementarity-determining regions (CDRs) that mediate binding to target antigens. Unfortunately, hydrophobic CDRs can also promote antibody aggregation, which is especially concerning for therapeutic antibodies due to the immunogenicity of antibody aggregates. Here we investigate how the sequences of CDRs within single-domain (V(H)) antibodies specific for the Alzheimer's amyloid β peptide can be engineered to resist aggregation without reducing binding affinity.

Polyphenolic disaccharides endow proteins with unusual resistance to aggregation.

Protein aggregation is a common problem during the purification and formulation of therapeutic proteins. Here we report that polyphenolic disaccharides are unusually effective at preventing protein aggregation. We find that two polyphenolic glycosides-naringin and rutin-endow diverse proteins with the ability to unfold without aggregating when heated, as well as the ability to refold without aggregating when cooled at low glycoside concentrations (<5 mM).

Structure-based design of conformation- and sequence-specific antibodies against amyloid β.

Conformation-specific antibodies that recognize aggregated proteins associated with several conformational disorders (e.g., Parkinson and prion diseases) are invaluable for diagnostic and therapeutic applications.

Site-specific structural analysis of a yeast prion strain with species-specific seeding activity.

Prion proteins misfold and aggregate into multiple infectious strain variants that possess unique abilities to overcome prion species barriers, yet the structural basis for the species-specific infectivities of prion strains is poorly understood. Therefore, we have investigated the site-specific structural properties of a promiscuous chimeric form of the yeast prion Sup35 from Saccharomyces cerevisiae and Candida albicans. The Sup35 chimera forms two strain variants, each of which selectively infect one species but not the other.

Mutational analysis of domain antibodies reveals aggregation hotspots within and near the complementarity determining regions.

High-affinity antibodies are critical for numerous diagnostic and therapeutic applications, yet their utility is limited by their variable propensity to aggregate either at low concentrations for antibody fragments or high concentrations for full-length antibodies. Therefore, determining the sequence and structural features that differentiate aggregation-resistant antibodies from aggregation-prone ones is critical to improving their activity. We have investigated the molecular origins of antibody aggregation for human V(H) domain antibodies that differ only in the sequence of the loops containing their complementarity determining regions (CDRs), yet such antibodies possess dramatically different aggregation propensities in a manner not correlated with their conformational stabilities.

Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers.

Misfolded proteins associated with diverse aggregation disorders assemble not only into a single toxic conformer but rather into a suite of aggregated conformers with unique biochemical properties and toxicities. To what extent small molecules can target and neutralize specific aggregated conformers is poorly understood. Therefore, we have investigated the capacity of resveratrol to recognize and remodel five conformers (monomers, soluble oligomers, non-toxic oligomers, fibrillar intermediates, and amyloid fibrils) of the Abeta1-42 peptide associated with Alzheimer disease.