Publications by authors named "Matthew Harrington"

Marine mussels fabricate tough collagenous fibers known as byssal threads to anchor themselves. Threads are produced individually in minutes via secretion of liquid crystalline (LC) collagenous precursors (preCols); yet the physical and chemical parameters influencing thread formation remain unclear. Here, we characterized the structural anisotropy of native and artificially induced threads using quantitative polarized light microscopy and transmission electron microscopy to elucidate spontaneous vs regulated aspects of thread assembly, discovering that preCol LC phases form aligned domains of several hundred microns, but not the cm-level alignment of native threads.

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Article Synopsis
  • Osteogenesis imperfecta (OI) is a genetic bone disorder that causes low bone density and frequent fractures, primarily treated with bisphosphonates in children, while adult treatment options are limited.
  • The ASTEROID trial tested a new treatment, setrusumab, which showed improvements in bone density and strength for adults with OI types I, III, and IV.
  • Analysis of bone biopsies revealed that while treatment with setrusumab did not significantly change the bone matrix properties, it did increase bone mass, suggesting that the fragility associated with OI may be due to other factors beyond just mineral content and matrix structure.
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Background: Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life.

Objective: We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs.

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Zebra and quagga mussels () are invasive freshwater biofoulers that perpetrate devastating economic and ecological impact. Their success depends on their ability to anchor onto substrates with protein-based fibers known as byssal threads. Yet, compared to other mussel lineages, little is understood about the proteins comprising their fibers or their evolutionary history.

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The mussel byssus stem provides a strong and compact mechanically mismatched biointerface between living tissue and a nonliving biopolymer. Yet, in a poorly understood process, mussels can simply jettison their entire byssus, rebuilding a new one in just hours. We characterized the structure and composition of the byssus biointerface using histology, confocal Raman mapping, phase contrast-enhanced microcomputed tomography, and advanced electron microscopy, revealing a sophisticated junction consisting of abiotic biopolymer sheets interdigitated between living extracellular matrix.

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Background: Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with antibody-drug conjugates, despite tens of clinical trials.

Methods: A systematic review of randomized controlled trials evaluating antibody-drug conjugate efficacy in anticancer treatment was conducted.

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Nature is rich with examples of highly specialized biological materials produced by organisms for functions, including defense, hunting, and protection. Along these lines, velvet worms (Onychophora) expel a protein-based slime used for hunting and defense that upon shearing and dehydration forms fibers as stiff as thermoplastics. These fibers can dissolve back into their precursor proteins in water, after which they can be drawn into new fibers, providing biological inspiration to design recyclable materials.

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Taking advantage of their thixotropic behavior, microporosity, and modular properties, granular hydrogels formed from jammed hydrogel microparticles have emerged as an exciting class of soft, injectable materials useful for numerous applications, ranging from the production of biomedical scaffolds for tissue repair to the therapeutic delivery of drugs and cells. Recently, the annealing of hydrogel microparticles in situ to yield a porous bulk scaffold has shown numerous benefits in regenerative medicine, including tissue-repair applications. Current annealing techniques, however, mainly rely either on covalent connections, which produce static scaffolds, or transient supramolecular interactions, which produce dynamic but mechanically weak hydrogels.

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For prey capture and defense, velvet worms eject an adhesive slime which has been established as a model system for recyclable complex liquids. Triggered by mechanical agitation, the liquid bio-adhesive rapidly transitions into solid fibers. In order to understand this mechanoresponsive behavior, here, the nanostructural organization of slime components are studied using small-angle scattering with neutrons and X-rays.

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Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 10  Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 10  Pa in storage modulus is used.

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Mistletoe viscin is a natural cellulosic adhesive consisting of hierarchically organized cellulose microfibrils (CMFs) surrounded by a humidity-responsive matrix that enables mechanical drawing into stiff and sticky fibers. Here, we explored the processability and adhesive capacity of viscin and demonstrated its potential as a source material for various material applications, as well as a source for bioinspired design. Specifically, we revealed that viscin fibers exhibit humidity-activated self-adhesive properties that enable "contact welding" into complex 2D and 3D architectures under ambient conditions.

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Functionally graded interfaces are prominent in biological tissues and are used to mitigate stress concentrations at junctions between mechanically dissimilar components. Biological mechanical gradients serve as important role models for bioinspired design in technically and biomedically relevant applications. However, this necessitates elucidating exactly how natural gradients mitigate mechanical mismatch and how such gradients are fabricated.

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There is an urgent need to improve the sustainability of the materials we produce and use. Here, we explore what humans can learn from nature about how to sustainably fabricate polymeric fibers with excellent material properties by reviewing the physical and chemical aspects of materials processing distilled from diverse model systems, including spider silk, mussel byssus, velvet worm slime, hagfish slime, and mistletoe viscin. We identify common and divergent strategies, highlighting the potential for bioinspired design and technology transfer.

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Mussels () adhere to hard surfaces in intertidal marine habitats with a porous underwater glue called the byssus plaque. The plaque is an established role model for bioinspired underwater glues and comprises at least six proteins, most of which are highly cationic and enriched in the post-translationally modified amino acid 3,4-dihydroxyphenylalanine (DOPA). While much is known about the chemistry of plaque adhesion, less is understood about the natural plaque formation process.

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We have identified a novel shell protein, accripin11, as a major soluble component of the calcitic prisms of the fan mussel Pinna nobilis. Initially retrieved from a cDNA library, its full sequence is confirmed here by transcriptomic and proteomic approaches. The sequence of the mature protein is 103 residues with a theoretical molecular weight of 11 kDa and is moderately acidic (pI 6.

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Hepatotoxicity is a major immune-related adverse event that may become life-threatening. The impact of adding immune checkpoint blockade (ICB) to systemic therapy on the incidence of hepatotoxicity remains unknown. We performed a systematic review and meta-analysis to compare the incidence of hepatotoxicity among patients with cancer who received therapy with and without addition of ICB.

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Because of structural similarities with type-I animal collagen, recombinant bacterial collagen-like proteins have been progressively used as a source of collagen for biomaterial applications. However, the intracellular expression combined with current costly and time-consuming chromatography methods for purification makes the large-scale production of recombinant bacterial collagen challenging. Here, we report the use of an adapted secretion pathway, used natively byto secrete curli fibers, for extracellular secretion of the bacterial collagen.

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To anchor in seashore habitats, mussels fabricate adhesive byssus fibers that are mechanically reinforced by protein-metal coordination mediated by 3,4-dihydroxyphenylalanine (DOPA). The mechanism by which metal ions are integrated during byssus formation remains unknown. In this study, we investigated the byssus formation process in the blue mussel, , combining traditional and advanced methods to identify how and when metals are incorporated.

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Certain organisms including species of mollusks, polychaetes, onychophorans and arthropods produce exceptional polymeric materials outside their bodies under ambient conditions using concentrated fluid protein precursors. While much is understood about the structure-function relationships that define the properties of such materials, comparatively less is understood about how such materials are fabricated and specifically, how their defining hierarchical structures are achieved via bottom-up assembly. Yet this information holds great potential for inspiring sustainable manufacture of advanced polymeric materials with controlled multi-scale structure.

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Detector technology plays a pivotal role in high-resolution and high-throughput cryo-EM structure determination. Compared with the first-generation, single-electron counting direct detection camera (Gatan K2), the latest K3 camera is faster, larger, and now offers a correlated-double sampling mode (CDS). Importantly this results in a higher DQE and improved throughput compared to its predecessor.

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Objectives: The aim of this study was to assess the impact of aortic valve replacement (AVR) on survival in patients with each subclass of low-gradient (LG) aortic stenosis (AS) and to compare outcomes following surgical AVR (SAVR) and transcatheter AVR (TAVR).

Background: LG severe AS encompasses a wide variety of pathophysiology, including classical low-flow, LG (LF-LG), paradoxical LF-LG, and normal-flow, LG (NF-LG) AS, and uncertainty exists regarding the impact of AVR on each subclass of LG AS.

Methods: PubMed and Embase were queried through October 2020 to identify studies comparing survival with different management strategies (SAVR, TAVR, and conservative) in patients with LG AS.

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Protein-based biological materials are important role models for the design and fabrication of next generation advanced polymers. Marine mussels ( spp.) fabricate hierarchically structured collagenous fibers known as byssal threads bottom-up supramolecular assembly of fluid protein precursors.

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Objectives: Hemoptysis is a complication in cystic fibrosis (CF) patients, and is associated with pulmonary exacerbations and hospitalizations. Pancreatic insufficiency is common in CF patients, and therefore these patients may benefit from the use of vitamin K therapy.

Methods: This was an observational study conducted in adult CF patients aiming to describe the utilization of vitamin K therapy in the setting of hemoptysis during an acute CF pulmonary exacerbation.

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Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition RELEASE DATE: September 20, 2019 PRIOR VERSION: Not applicable DEVELOPER: American Society for Bone and Mineral Research Task Force and Multistakeholder Coalition FUNDING SOURCE: American Society for Bone and Mineral Research and the Center for Medical Technology Policy TARGET POPULATION: Adults 65 years or older with a hip or vertebral fracture. This review will focus on the core recommendations and their application in the practice of hospital medicine.

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Article Synopsis
  • * It summarizes current knowledge about mucus structures and showcases ongoing research efforts worldwide, focusing on the properties and functions of mucus and its hierarchical organization.
  • * The authors call for a more organized approach to mucus research, aiming to create a comprehensive knowledge base for comparative studies (referred to as "mucomics") to ultimately inspire the design of new materials based on animal mucus features.
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