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Article ; Online: Advances in bone-targeting drug delivery: Emerging strategies using adeno-associated virus.

Sato, Tadatoshi / Chaugule, Sachin / Greenblatt, Matthew / Gao, Guangping / Shim, Jae-Hyuck

2024

Abstract: The development of bone-targeting drug delivery systems holds immense promise for improving the treatment of skeletal diseases. By precisely delivering therapeutic agents to the affected areas of bone, these strategies can enhance drug efficacy, minimize ...

Abstract	The development of bone-targeting drug delivery systems holds immense promise for improving the treatment of skeletal diseases. By precisely delivering therapeutic agents to the affected areas of bone, these strategies can enhance drug efficacy, minimize off-target effects, and promote patient adherence, ultimately leading to improved treatment outcomes and an enhanced quality of life for patients. This review aims to provide an overview of the current state of affinity-based bone-targeting agents and recent breakthroughs in innovative bone-targeting adeno-associated virus (AAV) strategies to treat skeletal diseases in mice. In particular, this review will delve into advanced AAV engineering, including AAV serotype selection for bone targeting and capsid modifications for bone-specific tropism. Additionally, we will highlight recent advancements in AAV-mediated gene therapy for skeletal diseases and discuss challenges and future directions of this promising therapeutic approach.
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2024.034
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Zs.A 2988: Show issues

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Article ; Online: Depression and Medicine Use among Older Adults during the COVID-19 Pandemic: The Role of Psychosocial Resources and COVID-19 Perceived Susceptibility.

Greenblatt-Kimron, Lee / Shinan-Altman, Shiri / Alperin, Mordechai / Levkovich, Inbar

International journal of environmental research and public health

2023 Volume 20, Issue 4

Abstract: A relationship was found between the COVID-19 pandemic and depression among older adults and between depressed mood and increased use of antidepressant medication among older adults during the pandemic. With the aim of broadening the understanding of ... ...

Abstract	A relationship was found between the COVID-19 pandemic and depression among older adults and between depressed mood and increased use of antidepressant medication among older adults during the pandemic. With the aim of broadening the understanding of these relationships, the study examined whether COVID-19 perceived susceptibility mediates the relationship between psychosocial resources (optimism and perceived social support) and depressive symptoms and medication use. Participants included 383 older adults (
MeSH term(s)	Humans ; Aged ; COVID-19 ; Depression ; Pandemics ; Drug-Related Side Effects and Adverse Reactions ; Medicine
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20043398
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Article ; Online: Negatively charged, intrinsically disordered regions can accelerate target search by DNA-binding proteins.

Wang, Xi / Bigman, Lavi S / Greenblatt, Harry M / Yu, Binhan / Levy, Yaakov / Iwahara, Junji

Nucleic acids research

2023 Volume 51, Issue 10, Page(s) 4701–4712

Abstract: In eukaryotes, many DNA/RNA-binding proteins possess intrinsically disordered regions (IDRs) with large negative charge, some of which involve a consecutive sequence of aspartate (D) or glutamate (E) residues. We refer to them as D/E repeats. The ... ...

Abstract	In eukaryotes, many DNA/RNA-binding proteins possess intrinsically disordered regions (IDRs) with large negative charge, some of which involve a consecutive sequence of aspartate (D) or glutamate (E) residues. We refer to them as D/E repeats. The functional role of D/E repeats is not well understood, though some of them are known to cause autoinhibition through intramolecular electrostatic interaction with functional domains. In this work, we investigated the impacts of D/E repeats on the target DNA search kinetics for the high-mobility group box 1 (HMGB1) protein and the artificial protein constructs of the Antp homeodomain fused with D/E repeats of varied lengths. Our experimental data showed that D/E repeats of particular lengths can accelerate the target association in the overwhelming presence of non-functional high-affinity ligands ('decoys'). Our coarse-grained molecular dynamics (CGMD) simulations showed that the autoinhibited proteins can bind to DNA and transition into the uninhibited complex with DNA through an electrostatically driven induced-fit process. In conjunction with the CGMD simulations, our kinetic model can explain how D/E repeats can accelerate the target association process in the presence of decoys. This study illuminates an unprecedented role of the negatively charged IDRs in the target search process.
MeSH term(s)	DNA/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Intrinsically Disordered Proteins/chemistry ; Intrinsically Disordered Proteins/metabolism ; Molecular Dynamics Simulation ; Kinetics ; Homeodomain Proteins/chemistry ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Synthetic Biology
Chemical Substances	DNA (9007-49-2) ; DNA-Binding Proteins ; Intrinsically Disordered Proteins ; Homeodomain Proteins
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad045
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Zs.A 1067: Show issues

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Article ; Online: What Are the Molecular Requirements for Protein Sliding along DNA?

Bigman, Lavi S / Greenblatt, Harry M / Levy, Yaakov

The journal of physical chemistry. B

2021 Volume 125, Issue 12, Page(s) 3119–3131

Abstract: DNA-binding proteins rely on linear diffusion along the longitudinal DNA axis, supported by their nonspecific electrostatic affinity for DNA, to search for their target recognition sites. One may therefore expect that the ability to engage in linear ... ...

Abstract	DNA-binding proteins rely on linear diffusion along the longitudinal DNA axis, supported by their nonspecific electrostatic affinity for DNA, to search for their target recognition sites. One may therefore expect that the ability to engage in linear diffusion along DNA is universal to all DNA-binding proteins, with the detailed biophysical characteristics of that diffusion differing between proteins depending on their structures and functions. One key question is whether the linear diffusion mechanism is defined by translation coupled with rotation, a mechanism that is often termed sliding. We conduct coarse-grained and atomistic molecular dynamics simulations to investigate the minimal requirements for protein sliding along DNA. We show that coupling, while widespread, is not universal. DNA-binding proteins that slide along DNA transition to uncoupled translation-rotation (i.e., hopping) at higher salt concentrations. Furthermore, and consistently with experimental reports, we find that the sliding mechanism is the less dominant mechanism for some DNA-binding proteins, even at low salt concentrations. In particular, the toroidal PCNA protein is shown to follow the hopping rather than the sliding mechanism.
MeSH term(s)	DNA/metabolism ; DNA-Binding Proteins/metabolism ; Diffusion ; Molecular Dynamics Simulation ; Protein Binding ; Static Electricity
Chemical Substances	DNA-Binding Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2021-03-23
Publishing country	United States
Document type	Journal Article
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.1c00757
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Article ; Online: Capacity for large language model chatbots to aid in orthopedic management, research, and patient queries.

Sosa, Branden R / Cung, Michelle / Suhardi, Vincentius J / Morse, Kyle / Thomson, Andrew / Yang, He S / Iyer, Sravisht / Greenblatt, Matthew B

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2024 Volume 42, Issue 6, Page(s) 1276–1282

Abstract: Large language model (LLM) chatbots possess a remarkable capacity to synthesize complex information into concise, digestible summaries across a wide range of orthopedic subject matter. As LLM chatbots become widely available they will serve as a powerful, ...

Abstract	Large language model (LLM) chatbots possess a remarkable capacity to synthesize complex information into concise, digestible summaries across a wide range of orthopedic subject matter. As LLM chatbots become widely available they will serve as a powerful, accessible resource that patients, clinicians, and researchers may reference to obtain information about orthopedic science and clinical management. Here, we examined the performance of three well-known and easily accessible chatbots-ChatGPT, Bard, and Bing AI-in responding to inquiries relating to clinical management and orthopedic concepts. Although all three chatbots were found to be capable of generating relevant responses, ChatGPT outperformed Bard and BingAI in each category due to its ability to provide accurate and complete responses to orthopedic queries. Despite their promising applications in clinical management, shortcomings observed included incomplete responses, lack of context, and outdated information. Nonetheless, the ability for these LLM chatbots to address these inquires has largely yet to be evaluated and will be critical for understanding the risks and opportunities of LLM chatbots in orthopedics.
MeSH term(s)	Humans ; Orthopedics
Language	English
Publishing date	2024-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25782
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Zs.A 1879: Show issues

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Article ; Online: The performance of artificial intelligence chatbot large language models to address skeletal biology and bone health queries.

Cung, Michelle / Sosa, Branden / Yang, He S / McDonald, Michelle M / Matthews, Brya G / Vlug, Annegreet G / Imel, Erik A / Wein, Marc N / Stein, Emily Margaret / Greenblatt, Matthew B

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2024

Abstract: Artificial intelligence (AI) chatbots utilizing large language models (LLMs) have recently garnered significant interest due to their ability to generate humanlike responses to user inquiries in an interactive dialog format. While these models are being ... ...

Abstract	Artificial intelligence (AI) chatbots utilizing large language models (LLMs) have recently garnered significant interest due to their ability to generate humanlike responses to user inquiries in an interactive dialog format. While these models are being increasingly utilized to obtain medical information by patients, scientific and medical providers, and trainees to address biomedical questions, their performance may vary from field to field. The opportunities and risks these chatbots pose to the widespread understanding of skeletal health and science are unknown. Here we assess the performance of 3 high-profile LLM chatbots, Chat Generative Pre-Trained Transformer (ChatGPT) 4.0, BingAI, and Bard, to address 30 questions in 3 categories: basic and translational skeletal biology, clinical practitioner management of skeletal disorders, and patient queries to assess the accuracy and quality of the responses. Thirty questions in each of these categories were posed, and responses were independently graded for their degree of accuracy by four reviewers. While each of the chatbots was often able to provide relevant information about skeletal disorders, the quality and relevance of these responses varied widely, and ChatGPT 4.0 had the highest overall median score in each of the categories. Each of these chatbots displayed distinct limitations that included inconsistent, incomplete, or irrelevant responses, inappropriate utilization of lay sources in a professional context, a failure to take patient demographics or clinical context into account when providing recommendations, and an inability to consistently identify areas of uncertainty in the relevant literature. Careful consideration of both the opportunities and risks of current AI chatbots is needed to formulate guidelines for best practices for their use as source of information about skeletal health and biology.
Language	English
Publishing date	2024-01-04
Publishing country	England
Document type	Journal Article
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1093/jbmr/zjad007
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Zs.A 2142: Show issues

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Article ; Online: Portal vein thrombosis in a patient known for congenital afibrinogenemia.

Greenblatt, Matthew / Cloutier, Stéphanie / Lemelin, Valery

Haemophilia : the official journal of the World Federation of Hemophilia

2020 Volume 26, Issue 6, Page(s) e331–e333

MeSH term(s)	Afibrinogenemia/congenital ; Female ; Humans ; Middle Aged ; Portal Vein/pathology ; Venous Thrombosis/physiopathology
Language	English
Publishing date	2020-07-14
Publishing country	England
Document type	Letter
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14092
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Zs.A 4249: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 450: Show issues

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Article ; Online: Poly(Vinyl Alcohol)-Hydrogel Microparticles with Soft Barrier Shell for the Encapsulation of Micrococcus luteus.

Mafi, Mahsa / Kushmaro, Ariel / Greenblatt, Charles / Agarwal, Seema / Greiner, Andreas

Macromolecular bioscience

2021 Volume 21, Issue 5, Page(s) e2000419

Abstract: ... transfer into the PVA core containing living Micrococcus luteus (M. luteus). Results show ... term for the biological activity of encapsulated M. luteus. ...

Abstract	The encapsulation of bacteria in polymers results in hybrid materials that are essential for the long-term biological activity of bacteria and formulations in practical applications. Here, the problem of bacterial escape and the exchange of metabolism products from hydrogel microparticles within an aqueous environment are addressed. Bacteria are encapsulated in chemically cross-linked poly(vinyl alcohol) (PVA) hydrogel-microparticles followed by their encapsulation in a pH-responsive and soft antibacterial shell of poly(N,N-diethylamino ethyl methacrylate) (PDEAEMA). This polymer shell acts selectively with regards to the mass transport in and out of the microparticle core and is affected by environmental parameters, such as pH and antibacterial effect. The pH-responsive PDEAEMA shell forms an open porous structure that accelerates nutrient transfer into the PVA core containing living Micrococcus luteus (M. luteus). Results show that the antibacterial effect of PDEAEMA retards the escape of bacteria up to 35 days when the shell is open. Additionally, the permeation of a small molecule into the gel, for example, methylene blue dye through the core/open-shell structure, certifies a flexible barrier for mass transport, which is required in the long term for the biological activity of encapsulated M. luteus.
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry ; Hydrogen-Ion Concentration ; Micrococcus luteus/chemistry ; Microscopy, Electron, Scanning ; Particle Size ; Polyvinyl Alcohol/chemistry
Chemical Substances	Anti-Bacterial Agents ; polyvinyl alcohol hydrogel ; Hydrogel, Polyethylene Glycol Dimethacrylate (25852-47-5) ; Polyvinyl Alcohol (9002-89-5)
Language	English
Publishing date	2021-03-13
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2039130-4
ISSN	1616-5195 ; 1616-5187
ISSN (online)	1616-5195
ISSN	1616-5187
DOI	10.1002/mabi.202000419
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Article ; Online: Pretreatment Methods for Human Nasopharyngeal Swabs to Increase the Signal to Noise Ratio of High Sensitivity Immunoassays.

Chen, Hui / Feng, Sheng / Zhou, Wan / Li, Zhao / Richard-Greenblatt, Melissa / Wang, Ping

ACS measurement science au

2022 Volume 2, Issue 5, Page(s) 414–421

Abstract: Mucous samples collected through nasopharyngeal (NP) swabs are considered gold standard specimens for the detection of respiratory pathogens. Matrices of these highly viscous samples often cause significant background noises in immunoassays, especially ... ...

Abstract	Mucous samples collected through nasopharyngeal (NP) swabs are considered gold standard specimens for the detection of respiratory pathogens. Matrices of these highly viscous samples often cause significant background noises in immunoassays, especially immunoassays with high sensitivity. We demonstrated such nonspecific background signals in both a chemiluminescence enzyme-linked immunosorbent assay (ELISA) and a novel highly sensitive immunoassay called Microbubbling SARS-CoV-2 Antigen Assay (MSAA). We developed and demonstrated the effectiveness of two quick sample pretreatment methods, filtration and preadsorption, to decrease nonspecific signals and increase the signal-to-noise ratio (SNR). Using these pretreatment methods, the SNR (at 3.6 × 10
Language	English
Publishing date	2022-06-29
Publishing country	United States
Document type	Journal Article
ISSN	2694-250X
ISSN (online)	2694-250X
DOI	10.1021/acsmeasuresciau.2c00024
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Article ; Online: Emergent symmetry in a low-dimensional superconductor on the edge of Mottness.

Chudzinski, P / Berben, M / Xu, Xiaofeng / Wakeham, N / Bernáth, B / Duffy, C / Hinlopen, R D H / Hsu, Yu-Te / Wiedmann, S / Tinnemans, P / Jin, Rongying / Greenblatt, M / Hussey, N E

Science (New York, N.Y.)

2023 Volume 382, Issue 6672, Page(s) 792–796

Abstract: Upon cooling, condensed-matter systems typically transition into states of lower symmetry. The converse-i.e., the emergence of higher symmetry at lower temperatures-is extremely rare. In this work, we show how an unusually isotropic magnetoresistance in ... ...

Abstract	Upon cooling, condensed-matter systems typically transition into states of lower symmetry. The converse-i.e., the emergence of higher symmetry at lower temperatures-is extremely rare. In this work, we show how an unusually isotropic magnetoresistance in the highly anisotropic, one-dimensional conductor Li
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abp8948
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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