Enhanced crude oil degradation observed in sea ice following bioaugmentation with arctic bacteria.

Petroleum-derived contamination is a growing hazard for the Arctic Ocean and northern marine transportation corridors. In northern settings where the accessibility to oil spills can be limited, natural attenuation is the most promising remediation process. The goal of the presented research is to evaluate the impact of biodegradation on crude oil inside sea ice.

Genomic signatures of cold adaptation in the family Colwelliaceae.

Psychrophily is a phenotype describing microbial growth at low temperatures; elucidating the biomolecular and genomic adaptations necessary for survival in the cold is important for understanding life in extreme environments on Earth and in outer space. We used comparative genomics and temperature growth experiments of bacteria from the family Colwelliaceae to identify genomic factors correlated with optimal growth temperature (OGT). A phylogenomic analysis of 67 public and 39 newly sequenced strains revealed three main clades of Colwelliaceae.

Comparative Efficacy of Advanced Therapies in the Treatment of Radiographic Axial Spondyloarthritis or Ankylosing Spondylitis as Evaluated by the ASDAS Low Disease Activity Criteria.

Introduction: With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations.

Methods: A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS.

Stepping-Stone CBH: Benchmark and Application of a Multilayered Isodesmic-Based Correction Scheme.

We present a generalization of the connectivity-based hierarchy (CBH) of isodesmic-based correction schemes to a multilayered fragmentation platform for overall cost reduction while retaining high accuracy. The newly developed multilayered CBH approach, called stepping-stone CBH (SSCBH), is benchmarked on a diverse set of 959 medium-sized organic molecules. Applying SSCBH corrections to the PBEh-D3 density functional resulted in an average error of 0.

Prevalence and Overlap of Cardiac, Renal, and Metabolic Conditions in US Adults, 1999-2020.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date.

Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time.

Approaching Coupled Cluster Accuracy with Density Functional Theory Using the Generalized Connectivity-Based Hierarchy.

This Perspective reviews connectivity-based hierarchy (CBH), a systematic hierarchy of error-cancellation schemes developed in our group with the goal of achieving chemical accuracy using inexpensive computational techniques ("coupled cluster accuracy with DFT"). The hierarchy is a generalization of Pople's isodesmic bond separation scheme that is based only on the structure and connectivity and is applicable to any organic and biomolecule consisting of covalent bonds. It is formulated as a series of rungs involving increasing levels of error cancellation on progressively larger fragments of the parent molecule.

Interpretable Graph-Network-Based Machine Learning Models via Molecular Fragmentation.

Chemists have long benefitted from the ability to understand and interpret the predictions of computational models. With the current shift to more complex deep learning models, in many situations that utility is lost. In this work, we expand on our previously work on computational thermochemistry and propose an interpretable graph network, FragGraph(nodes), that provides decomposed predictions into fragment-wise contributions.

Quantitative Prediction of Vertical Ionization Potentials from DFT via a Graph-Network-Based Delta Machine Learning Model Incorporating Electronic Descriptors.

While accurate wave function theories like CCSD(T) are capable of modeling molecular chemical processes, the associated steep computational scaling renders them intractable for treating large systems or extensive databases. In contrast, density functional theory (DFT) is much more computationally feasible yet often fails to quantitatively describe electronic changes in chemical processes. Herein, we report an efficient delta machine learning (ΔML) model that builds on the Connectivity-Based Hierarchy (CBH) scheme─an error correction approach based on systematic molecular fragmentation protocols─and achieves coupled cluster accuracy on vertical ionization potentials by correcting for deficiencies in DFT.

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis.

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.

Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region.

A Fragmentation-Based Graph Embedding Framework for QM/ML.

We introduce a new fragmentation-based molecular representation framework "FragGraph" for QM/ML methods involving embedding fragment-wise fingerprints onto molecular graphs. Our model is specifically designed for delta machine learning (Δ-ML) with the central goal of correcting the deficiencies of approximate methods such as DFT to achieve high accuracy. Our framework is based on a judicious combination of ideas from fragmentation, error cancellation, and a state-of-the-art deep learning architecture.

Changing Medical Education When Change Is Hard: Implementing an Interdepartmental Entrustable Professional Activity.

Background: Entrustable professional activities (EPAs) are a new tool for assessing learners that represents a significant movement in graduate medical education (GME) toward competency-based assessment and serves as a bridge between milestones and clinical practice. Whenever a major change is implemented to any system, resistance to change is expected. Many change management models have been proposed to overcome this resistance; a newer model is outlined in the book .

Effective Molecular Descriptors for Chemical Accuracy at DFT Cost: Fragmentation, Error-Cancellation, and Machine Learning.

Recent advances in theoretical thermochemistry have allowed the study of small organic and bio-organic molecules with high accuracy. However, applications to larger molecules are still impeded by the steep scaling problem of highly accurate quantum mechanical (QM) methods, forcing the use of approximate, more cost-effective methods at a greatly reduced accuracy. One of the most successful strategies to mitigate this error is the use of systematic error-cancellation schemes, in which highly accurate QM calculations can be performed on small portions of the molecule to construct corrections to an approximate method.

The effects of augmenting clozapine with oxytocin in schizophrenia: An initial case series.

Background: Debilitating symptoms of schizophrenia often persist after sustained treatment with atypical antipsychotics. To date, clozapine has been the most effective of the atypical antipsychotics; however, negative symptoms may persist, indicating a critical need to develop augmenting treatment approaches.

Methods: A retrospective chart review evaluated outcomes for 5 young adult inpatients with treatment-resistant schizophrenia who were prescribed off-label oxytocin (OT; 10 IU/sublingual, 1 time per day, to 20 IU/sublingual, 3 times per day) after their therapeutic response to clozapine plateaued (dose range: 200 to 600 mg).

Implementation of Entrustable Professional Activities into a General Surgery Residency.

Objective: Concerns over resident ability to practice effectively after graduation have led to the competency-based medical education movement. Entrustable professional activities (EPAs) may facilitate competency-based medical education in surgery, but implementation is challenging. This manuscript describes 1 strategy used to implement EPAs into an academic general surgery residency.

Identification and Characterization of a Dominant Sulfolane-Degrading Rhodoferax sp. via Stable Isotope Probing Combined with Metagenomics.

Sulfolane is an industrial solvent and emerging organic contaminant affecting groundwater around the world, but little is known about microbes capable of biodegrading sulfolane or the pathways involved. We combined DNA-based stable isotope probing (SIP) with genome-resolved metagenomics to identify microorganisms associated with sulfolane biodegradation in a contaminated subarctic aquifer. In addition to 16S rRNA gene amplicon sequencing, we performed shotgun metagenomics on the C-labeled DNA to obtain functional and taxonomic information about the active sulfolane-degrading community.

Accurate Thermochemistry for Organic Cations via Error Cancellation using Connectivity-Based Hierarchy.

Connectivity-Based Hierarchy (CBH) is an effective error-cancellation scheme for the determination of chemically accurate thermochemical properties of a variety of organic and biomolecules. Neutral molecules and open-shell radicals have already been treated successfully by this approach utilizing inexpensive computational methods such as density functional theory. Herein, we present an extension of the method to a new class of molecules, specifically, organic cations.

Insane: James Holmes, Clark v. Arizona, and America's Insanity Defense.

Insanity is a legal term of art that changes definitions depending on the legal standard in American jurisprudence, which explains why a man who mental health professionals described as having an uncontrollable obsession with killing people can be found not insane and guilty. This Note addresses the current state of the Insanity Defense Reform Act of 1984 and its widespread implementation at the state level. Part II supplies background information on the history of the insanity defense and how it has transformed over the years in American jurisprudence.

The Development and Application of Random Match Probabilities to Firearm and Toolmark Identification.

The field of firearms and toolmark analysis has encountered deep scrutiny of late, stemming from a handful of voices, primarily in the law and statistical communities. While strong scrutiny is a healthy and necessary part of any scientific endeavor, much of the current criticism leveled at firearm and toolmark analysis is, at best, misinformed and, at worst, punditry. One of the most persistent criticisms stems from the view that as the field lacks quantified random match probability data (or at least a firm statistical model) with which to calculate the probability of a false match, all expert testimony concerning firearm and toolmark identification or source attribution is unreliable and should be ruled inadmissible.

The FHA domain determines Drosophila Chk2/Mnk localization to key mitotic structures and is essential for early embryonic DNA damage responses.

DNA damage responses, including mitotic centrosome inactivation, cell-cycle delay in mitosis, and nuclear dropping from embryo cortex, maintain genome integrity in syncytial Drosophila embryos. A conserved signaling kinase, Chk2, known as Mnk/Loki, is essential for the responses. Here we demonstrate that functional EGFP-Mnk expressed from a transgene localizes to the nucleus, centrosomes, interkinetochore/centromere region, midbody, and pseudocleavage furrows without DNA damage and in addition forms numerous foci/aggregates on mitotic chromosomes upon DNA damage.

An inter-order horizontal gene transfer event enables the catabolism of compatible solutes by Colwellia psychrerythraea 34H.

Colwellia is a genus of mostly psychrophilic halophilic Gammaproteobacteria frequently isolated from polar marine sediments and sea ice. In exploring the capacity of Colwellia psychrerythraea 34H to survive and grow in the liquid brines of sea ice, we detected a duplicated 37 kbp genomic island in its genome based on the abnormally high G + C content. This island contains an operon encoding for heterotetrameric sarcosine oxidase and is located adjacent to several genes used in the serial demethylation of glycine betaine, a compatible solute commonly used for osmoregulation, to dimethylglycine, sarcosine, and glycine.