Publications by authors named "LeBeau L"

Objective: This qualitative study aimed to examine how states implemented COVID-19 public health emergency-related federal policy flexibilities for opioid use disorder treatment from the perspective of state-level behavioral health policy makers. Recommendations are given for applying lessons learned to improve the long-term impact of these flexibilities on opioid use disorder treatment.

Methods: Eleven semistructured interviews were conducted with 13 stakeholders from six state governments, and transcripts were qualitatively coded.

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The physiological problem of chronic inflammation and its associated pathologies attract ongoing attention with regard to methods for their control. Current systemic pharmacological treatments present problematic side effects. Thus, the possibility of new anti-inflammatory compounds with differing mechanisms of action or biophysical properties is enticing.

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Usutu virus (USUV) and West Nile virus (WNV) are closely related emerging arboviruses belonging to the genus and posing global public health concerns. Although human infection by these viruses is mainly asymptomatic, both have been associated with neurological disorders such as encephalitis and meningoencephalitis. Since USUV and WNV are transmitted through the bite of an infected mosquito, the skin represents the initial site of virus inoculation and provides the first line of host defense.

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Background: Myocardial infarction is one of the leading causes of mortality worldwide; hence, there is an urgent need to discover novel cardioprotective strategies. Kynurenic acid (KYNA), a metabolite of the kynurenine pathway, has been previously reported to have cardioprotective effects. However, the mechanisms by which KYNA may be protective are still unclear.

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Carbon dots (CDs) are nanoparticles (NPs) with potential applications in the biomedical field. When in contact with biological fluids, most NPs are covered by a protein corona. As well, upon cell entry, most NP are sequestered in the lysosome.

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Cardiac complications are frequently found following a stroke in humans whose pathophysiological mechanism remains poorly understood. We used machine learning to analyse a large set of data from a metabolipidomic study assaying 630 metabolites in a rat stroke model to investigate metabolic changes affecting the heart within 72 h after a stroke. Twelve rats undergoing a stroke and 28 rats undergoing the sham procedure were investigated.

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Background: In March 2020, Veterans Health Administration (VHA) enacted policies to expand treatment for Veterans with opioid use disorder (OUD) during COVID-19. In this study, we evaluate whether COVID-19 and subsequent OUD treatment policies impacted receipt of therapy/counseling and medication for OUD (MOUD).

Methods: Using VHA's nationwide electronic health record data, we compared outcomes between a comparison cohort derived using data from prior to COVID-19 (October 2017-December 2019) and a pandemic-exposed cohort (January 2019-March 2021).

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Carbon dots are emerging nanoparticles (NPs) with tremendous applications, especially in the biomedical field. Herein is reported the first quantitative proteomic analysis of the protein corona formed on CDs with different surface charge properties. Four CDs were synthesized from citric acid and various amine group-containing passivation reagents, resulting in cationic NPs with increasing zeta (ζ)-potential and density of positive charges.

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Carbon nanomaterials, including carbon dots (CDs), form a growing family of engineered nanoparticles (NPs) with widespread applications. As the rapid expansion of nanotechnologies raises safety concerns, interaction of NPs with the immune system is receiving a lot of attention. Recent studies have reported that engineered NPs may induce macrophage death by pyroptosis.

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Inhaled transfection particles have to penetrate the mucus layer lining the airways to successfully deliver their therapeutic nucleic acid payload to target cells in the underlying epithelium. However, the in vitro models used for evaluating gene carrier efficiency often disregard this viscous defensive barrier. In this study, the two mucus-secreting cell lines NCI-H292 and Calu-3 were selected to develop a series of epithelial models displaying gradual mucus production.

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This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Q) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = -43.3 mV); CD-PEI600 (Q = 4.

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Importance: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.

Objective: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival.

Design, Setting, And Participants: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence.

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Background: As pharmacists assume a larger role in prenatal and preconception care, providing an evidence-based recommendation for a prenatal vitamin is essential.

Objectives: To identify the prenatal vitamins that community pharmacists are recommending to patients and compare the contents with national and international standards. The secondary objectives were to compare responses between the type of pharmacy (chain, grocery, or independent) and region of Michigan.

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In this work, we used an original experimental setup to examine the behavior of insoluble monolayers made with pH-sensitive lipids. Two kinds of unsaturated lipids were chosen: a cationic one (lipid ) bearing an ammonium headgroup and an anionic one (lipid ) terminated with an acidic phenol group. The lipids were deposited onto an air bubble interface maintained in an aqueous phase and, after stabilization, were subjected to a series of compressions performed at different pH values.

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With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches.

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Background: A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.

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Repetitive complete or incomplete pharyngeal collapses are leading to chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA) syndrome responsible for many metabolic disorders. In humans, an association between OSA and insulin resistance has been found independently of the degree of obesity. Based on our previous work showing that hypoxia applied to adipocytes led to cellular insulin resistance associated with caveolae flattening, we have investigated the effects of CIH on caveolae structuration in adipose tissue.

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Article Synopsis
  • PILC is a more aggressive form of invasive lobular carcinoma (ILC) linked to the activation of the PI3K/Akt/mTOR pathway, which leads to higher cell proliferation rates.
  • In a study, 85% of PILCs exhibited elevated proliferation markers (Ki67) compared to just 20% of ILCs, while differences in markers PTEN and pS6K1 were noted between the two types.
  • Gene analysis showed that PILCs overexpress genes related to cell cycle activation and repair, indicating they have distinct biological characteristics that may necessitate different therapeutic approaches.
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Alkylphospholipids (APLs) have elicited great interest as antitumor agents due to their unique mode of action on cell membranes. However, their clinical applications have been limited so far by high hemolytic activity. Recently, cationic prodrugs of erufosine, a most promising APL, have been shown to mediate efficient intracellular gene delivery, while preserving the antiproliferative properties of the parent APL.

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Importance: Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in the context of a phase 2 neoadjuvant platform trial.

Objective: To evaluate the association of pCR with event-free survival (EFS) and pCR with distant recurrence-free survival (DRFS) in subpopulations of women with high-risk operable breast cancer treated with standard therapy or one of several novel agents.

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Purpose: Hemolysis is a serious side effect of antitumor alkylphospholipids (APLs) that limits dose levels and is a constraint in their use in therapeutic regimen. Nine prodrugs of promising APLs (miltefosine, perifosine, and erufosine) were synthesized so as to decrease their membrane activity and improve their toxicity profile while preserving their antineoplastic potency.

Methods: The synthesis of the pro-APLs was straightforwardly achieved in one step starting from the parent APLs.

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Scaffold-assisted gene therapy is a highly promising tool to treat articular cartilage lesions upon direct delivery of chondrogenic candidate sequences. The goal of this study was to examine the feasibility and benefits of providing highly chondroreparative agents, the cartilage-specific sex-determining region Y-type high-mobility group 9 (SOX9) transcription factor or the transforming growth factor beta (TGF-β), to human bone marrow-derived mesenchymal stromal cells (hMSCs) via clinically adapted, independent recombinant adeno-associated virus (rAAV) vectors formulated with carbon dots (CDs), a novel class of carbon-dominated nanomaterials. Effective complexation and release of a reporter rAAV- vector was achieved using four different CDs elaborated from 1-citric acid and pentaethylenehexamine (CD-1); 2-citric acid, poly(ethylene glycol) monomethyl ether (MW 550 Da), and ,-dimethylethylenediamine (CD-2); 3-citric acid, branched poly(ethylenimine) (MW 600 Da), and poly(ethylene glycol) monomethyl ether (MW 2 kDa) (CD-3); and 4-citric acid and branched poly(ethylenimine) (MW 600 Da) (CD-4), allowing for the genetic modification of hMSCs.

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Sixteen cationic prodrugs of the antitumor alkylphospholipid (APL) erufosine were rationally synthesized to provide original gene delivery reagents with improved cytotoxicity profile. The DNA complexation properties of these cationic lipids were determined and associated transfection rates were measured. Furthermore, the self-assembly properties of the pro-erufosine compounds were investigated and their critical aggregation concentration was determined.

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Chromatin-mediated silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of chromatin-mediated silencing can result in genome rearrangements, particularly at intrinsically unstable regions of the genome such as transposons, satellite repeats, and repetitive gene clusters including the rRNA gene clusters (). It is thus expected that mutational or environmental conditions that compromise heterochromatin function might cause genome instability, and diseases associated with decreased epigenetic stability might exhibit genome changes as part of their aetiology.

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Carbon dots (CDs) are emerging nanomaterial in medicine and pharmacy. To explore the impact of physicochemical characteristics on their safety, we synthesized a library of 35 CDs exhibiting different size, charge, chemical composition and surface coating, using various starting materials (carbon source and passivation reagent) and carbonization procedures. The 35 CDs triggered different levels of viability loss when incubated with human macrophages at 3-200 µg/mL for 24 h.

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