Adaptive Measurement of Change in the Context of Item Parameter Drift.

Adaptive measurement of change (AMC) uses computerized adaptive testing (CAT) to measure and test the significance of intraindividual change on one or more latent traits. The extant AMC research has so far assumed that item parameter values are constant across testing occasions. Yet item parameters might change over time, a phenomenon termed item parameter drift (IPD).

Bioinformatic Analysis of Topoisomerase IIα Reveals Interdomain Interdependencies and Critical C-Terminal Domain Residues.

DNA Topoisomerase IIα (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis, including the PSICalc algorithm, Shannon entropy analysis, and other approaches.

Faith and facts: Exploring the intersection of religion and science among anatomy educators.

The intersection of religion and science often elicits polarizing views among scientists, though approximately half of American scientists identify as religious. Mounting evidence also supports the role of spirituality in comprehensive patient care. The purpose of this study was to explore the religiosity of faculty who teach in the anatomical sciences at U.

No Time to Relax and Unwind: Exploration of Topoisomerases and a Growing Field of Study.

With the topoisomerase field in its sixth decade [...

Inhibition of Topoisomerases by Metal Thiosemicarbazone Complexes.

Topoisomerases, common targets for anti-cancer therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effects of thiosemicarbazones (TSC) and metal-TSC complexes have been demonstrated to target several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition of topoisomerase II.

PSICalc: a novel approach to identifying and ranking critical non-proximal interdependencies within the overall protein structure.

Motivation: AlphaFold has been a major advance in predicting protein structure, but still leaves the problem of determining which sub-molecular components of a protein are essential for it to carry out its function within the cell. Direct coupling analysis predicts two- and three-amino acid contacts, but there may be essential interdependencies that are not proximal within the 3D structure. The problem to be addressed is to design a computational method that locates and ranks essential non-proximal interdependencies within a protein involving five or more amino acids, using large, multiple sequence alignments (MSAs) for both globular and intrinsically unstructured proteins.

Accessing hemodialysis clinics during the COVID-19 pandemic.

Transportation is a key element of access to healthcare. The COVID-19 pandemic posed unique and unforeseen challenges to patients receiving hemodialysis who rely on three times weekly transportation to receive their life-saving treatments, but there is little data on the problems they faced. This study explores the attitudes, fears, and concerns of hemodialysis patients during the pandemic with a focus on their travel to/from dialysis treatments.

Travel behaviour and greenhouse gas emissions during the COVID-19 pandemic: A case study in a university setting.

The year 2020 was characterized by a marked shift in daily travel patterns due to the COVID-19 pandemic. While we know that overall travel decreased, less is known about modal shift among those who continued to travel during the pandemic or about the impact of these travel-behaviour changes on transport-related greenhouse gas emissions. Focusing on a university setting and drawing from a travel survey conducted in Fall 2020 in Montreal, Canada (n = 3358), this study examines modal shifts and quantifies greenhouse gas emissions at three time periods in the year 2020: pre-pandemic, early pandemic, and later pandemic.

Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity.

Human topoisomerase IIα (TOP2A) is a vital nuclear enzyme involved in resolving knots and tangles in DNA during replication and cell division. TOP2A is a homodimer with a symmetrical, multidomain structure. While the N-terminal and core regions of the protein are well-studied, the C-terminal domain is poorly understood but is involved in enzyme regulation and is predicted to be intrinsically disordered.

Adaptive Measurement of Change: A Novel Method to Reduce Respondent Burden and Detect Significant Individual-Level Change in Patient-Reported Outcome Measures.

Objective: To describe the adaptive measurement of change (AMC) as a means to identify psychometrically significant change in reported function of hospitalized patients and to reduce respondent burden on follow-up assessments.

Design: The AMC method uses multivariate computerized adaptive testing (CAT) and psychometric hypothesis tests based in item response theory to more efficiently measure intra-individual change using the responses of a single patient over 2 or more testing occasions. Illustrations of the utility of AMC in clinical care and estimates of AMC-based item reduction are provided using the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT), a newly developed functional multidimensional CAT-based measurement of basic mobility, daily activities, and applied cognition.

Rapid buprenorphine microdosing for opioid use disorder in a hospitalized patient receiving very high doses of full agonist opioids for acute pain management: Titration, implementation barriers, and strategies to overcomes.

Conventional buprenorphine inductions for OUD are clinically useful but require patients to experience mild to moderate opioid withdrawal symptoms to avoid precipitated withdrawal. This may be intolerable/unreasonable for some, which may have precluded successful buprenorphine treatment in the past. Microdosing buprenorphine, allowing for full agonist opioid overlap, has emerged as a clinically useful strategy for those unable to complete conventional buprenorphine induction.

Cannabidiol oxidation product HU-331 is a potential anticancer cannabinoid-quinone: a narrative review.

Cannabidiol and related cannabinoids are under exploration for the treatment of a number of disease states. The cannabinoid-quinone HU-331 has been studied as a potential anticancer therapeutic. Previous studies provide evidence that HU-331 displays anticancer activity without some of the known adverse events associated with traditional anticancer agents.

Fusing subnational with national climate action is central to decarbonization: the case of the United States.

Approaches that root national climate strategies in local actions will be essential for all countries as they develop new nationally determined contributions under the Paris Agreement. The potential impact of climate action from non-national actors in delivering higher global ambition is significant. Sub-national action in the United States provides a test for how such actions can accelerate emissions reductions.

Synthesis and evaluation of etoposide and podophyllotoxin analogs against topoisomerase IIα and HCT-116 cells.

Etoposide is a widely-used anticancer agent that targets human type II topoisomerases. Evidence suggests that metabolism of etoposide in myeloid progenitor cells is associated with translocations involved in leukemia development. Previous studies suggest halogenation at the C-2' position of etoposide reduces metabolism.

Clarifying the Mechanism of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIα and IIβ.

Topoisomerase II is a nuclear enzyme involved in the maintenance of DNA and is an effective anticancer drug target. However, several clinical topoisomerase II-targeted agents display significant off-target toxicities and adverse events. Thus, it is important to continue characterizing compounds with activity against topoisomerase II.

Examining the Impact of Antimicrobial Fluoroquinolones on Human DNA Topoisomerase IIα and IIβ.

Fluoroquinolones are a class of widely prescribed antibiotics with a broad range of activity against Gram-positive, Gram-negative, and some atypical microbes. Unfortunately, these drugs are associated with significant adverse events including neuropathy, tendinopathy, cardiac rhythm abnormalities, and mental health side effects. The mechanism by which fluoroquinolones cause many of these toxicities is unknown.

Structural and Metal Ion Effects on Human Topoisomerase IIα Inhibition by α-(N)-Heterocyclic Thiosemicarbazones.

Our previous research has shown that α-(N)-heterocyclic thiosemicarbazone (TSC) metal complexes inhibit human topoisomerase IIα (TopoIIα), while the ligands without metals do not. To find out the structural elements of TSC that are important for inhibiting TopoIIα, we have synthesized two series of α-(N)-heterocyclic TSCs with various substrate ring segments, side chain substitutions, and metal ions, and we have examined their activities in TopoIIα-mediated plasmid DNA relaxation and cleavage assays. Our goal is to explore the structure-activity relationship of α-(N)-heterocyclic TSCs and their effect on TopoIIα.

HU-331 and Oxidized Cannabidiol Act as Inhibitors of Human Topoisomerase IIα and β.

Topoisomerase II is a critical enzyme in replication, transcription, and the regulation of chromatin topology. Several anticancer agents target topoisomerases in order to disrupt cell growth. Cannabidiol is a major non-euphoriant, pharmacologically active component of cannabis.

Two-Mechanism Model for the Interaction of Etoposide Quinone with Topoisomerase IIα.

Topoisomerase II is an essential nuclear enzyme involved in regulating DNA topology to facilitate replication and cell division. Disruption of topoisomerase II function by chemotherapeutic agents is in use as an effective strategy to fight cancer. Etoposide is an anticancer therapeutic that disrupts the catalytic cycle of topoisomerase II and stabilizes enzyme-bound DNA strand breaks.

Examination of the Impact of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIα.

Type II DNA topoisomerases resolve topological knots and tangles in DNA that result from routine cellular processes and are effective targets for anticancer therapeutics. To this end, thiosemicarbazones have been identified as having the ability to kill cancer cells from several cell lines. Literature evidence suggests that at least some thiosemicarbazones have an impact on topoisomerase II activity.

A decade of burn unit experience with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Clinical pathological diagnosis and risk factor awareness.

Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) is a rare and often fatal spectrum of mucocutaneous diseases usually attributable to severe adverse drug reactions. Burn units are referral centers for patients at the most extreme end of the disease continuum. Our burn center admits a much higher percentage of TEN (>30% BSA) cases than reported in most prior reviews.

HU-331 is a catalytic inhibitor of topoisomerase IIα.

Topoisomerases are essential enzymes that are involved in DNA metabolism. Topoisomerase II generates transient DNA strand breaks that are stabilized by anticancer drugs, such as doxorubicin, causing an accumulation of DNA damage. However, doxorubicin causes cardiac toxicity and, like etoposide and other topoisomerase II-targeted agents, can induce DNA damage, resulting in secondary cancers.

Catalytic core of human topoisomerase IIα: insights into enzyme-DNA interactions and drug mechanism.

Coordination between the N-terminal gate and the catalytic core of topoisomerase II allows the proper capture, cleavage, and transport of DNA during the catalytic cycle. Because the activities of these domains are tightly linked, it has been difficult to discern their individual contributions to enzyme-DNA interactions and drug mechanism. To further address the roles of these domains, we analyzed the activity of the catalytic core of human topoisomerase IIα.

Etoposide quinone is a covalent poison of human topoisomerase IIβ.

Etoposide is a topoisomerase II poison that is utilized to treat a broad spectrum of human cancers. Despite its wide clinical use, 2-3% of patients treated with etoposide eventually develop treatment-related acute myeloid leukemias (t-AMLs) characterized by rearrangements of the MLL gene. The molecular basis underlying the development of these t-AMLs is not well understood; however, previous studies have implicated etoposide metabolites (i.

Etoposide catechol is an oxidizable topoisomerase II poison.

Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic translocations.