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Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.
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The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.
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COVID-19 , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/epidemiologia , COVID-19/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , Adulto , Pandemias , Tempo para o Tratamento/estatística & dados numéricos , TireoidectomiaRESUMO
Max L. Lee was not included as an author in the original publication [...].
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Vessel electronic monitoring (EM) systems used in fisheries around the world apply a variety of cameras to record catch as it is brought on deck and during fish processing activities. In EM work conducted by the Center for Fisheries Electronic Monitoring at Mote (CFEMM) in the Gulf of Mexico commercial reef fish fishery, there was a need to improve upon current technologies to enhance camera views for accurate species identification of large sharks, particularly those that were released while underwater at the vessel side or underneath the hull. This paper describes how this problem was addressed with the development of the first known EM system integrated underwater camera (UCAM) with a specialized vessel-specific deployment device on a bottom longline reef fish vessel. Data are presented based on blind video reviews from CFEMM trained reviewers of the resulting UCAM video footage compared with video from only the overhead EM cameras from 68 gear retrievals collected from eight fishing trips. Results revealed that the UCAM was a successful tool for capturing clear underwater video footage of released large (>2m) sharks to enable reviewers to improve individual species identification, determination, and fate by 34.4%. This was particularly important for obtaining data on incidental catches of large protected shark species. It also provided clear underwater imagery of the presence of potential predators such as marine mammals close to the vessel, more specifically bottlenose dolphin (Tursiops truncatus) during gear retrieval, which often damaged or removed catch. This information is intended to assist researchers in need of gathering critical data on bycatch in close proximity to a vessel in which conventional overhead EM cameras are limited.
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Caniformia , Tubarões , Animais , Conservação dos Recursos Naturais/métodos , Pesqueiros , Golfo do México , EletrônicaRESUMO
The COVID-19 pandemic led to increased telehealth utilization in outpatient otolaryngology settings. While other studies on telehealth usage in otolaryngology settings have focused on demographic disparities during the pandemic, none have yet assessed how these demographic disparities have evolved from before versus after the pandemic. This study examines 4 recent consecutive years of demographic and clinical data from a large hospital system to investigate how the COVID-19 pandemic has changed demographic patterns in telehealth utilization. We demonstrate substantial increases in the number of otolaryngology patients participating in telehealth since the beginning of the COVID-19 pandemic but with no differences in patient distributions by race or ethnicity over time. We also found that telehealth patients, on average, were younger, more likely to be English-speaking, and more likely to be female. While these disparities widened slightly after the start of the pandemic, they were also present prior to the pandemic.
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Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.
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Quimiotaxia , Osteogênese , Animais , Coelhos , Células Endoteliais , Ligantes , Regeneração Óssea , Macrófagos , Diferenciação CelularAssuntos
Bursite , Humanos , Bursite/diagnóstico por imagem , Escápula , Biópsia Guiada por Imagem , TomografiaRESUMO
Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.
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Interface Osso-Implante , Longevidade , Humanos , Idoso , Desenvolvimento Ósseo , InflamaçãoRESUMO
Smart health applications have received significant attention in recent years. Novel applications hold significant promise to overcome many of the inconveniences faced by persons with disabilities throughout daily living. For people with blindness and low vision (BLV), environmental perception is compromised, creating myriad difficulties. Precise localization is still a gap in the field and is critical to safe navigation. Conventional GNSS positioning cannot provide satisfactory performance in urban canyons. 3D mapping-aided (3DMA) GNSS may serve as an urban GNSS solution, since the availability of 3D city models has widely increased. As a result, this study developed a real-time 3DMA GNSS-positioning system based on state-of-the-art 3DMA GNSS algorithms. Shadow matching was integrated with likelihood-based ranging 3DMA GNSS, generating positioning hypothesis candidates. To increase robustness, the 3DMA GNSS solution was then optimized with Doppler measurements using factor graph optimization (FGO) in a loosely-coupled fashion. This study also evaluated positioning performance using an advanced wearable system's recorded data in New York City. The real-time forward-processed FGO can provide a root-mean-square error (RMSE) of about 21 m. The RMSE drops to 16 m when the data is post-processed with FGO in a combined direction. Overall results show that the proposed loosely-coupled 3DMA FGO algorithm can provide a better and more robust positioning performance for the multi-sensor integration approach used by this wearable for persons with BLV.
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Sistemas de Informação Geográfica , Registros , Cegueira , Coleta de Dados , Humanos , Funções Verossimilhança , New YorkRESUMO
Despite the advent of effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) continues to pose major challenges, with extensive pathogenesis during acute and chronic infection prior to ART initiation and continued persistence in a reservoir of infected CD4 T cells during long-term ART. CD101 has recently been characterized to play an important role in CD4 Treg potency. Using the simian immunodeficiency virus (SIV) model of HIV infection in rhesus macaques, we characterized the role and kinetics of CD101+ CD4 T cells in longitudinal SIV infection. Phenotypic analyses and single-cell RNAseq profiling revealed that CD101 marked CD4 Tregs with high immunosuppressive potential, distinct from CD101- Tregs, and these cells also were ideal target cells for HIV/SIV infection, with higher expression of CCR5 and α4ß7 in the gut mucosa. Notably, during acute SIV infection, CD101+ CD4 T cells were preferentially depleted across all CD4 subsets when compared with their CD101- counterpart, with a pronounced reduction within the Treg compartment, as well as significant depletion in mucosal tissue. Depletion of CD101+ CD4 was associated with increased viral burden in plasma and gut and elevated levels of inflammatory cytokines. While restored during long-term ART, the reconstituted CD101+ CD4 T cells display a phenotypic profile with high expression of inhibitory receptors (including PD-1 and CTLA-4), immunsuppressive cytokine production, and high levels of Ki-67, consistent with potential for homeostatic proliferation. Both the depletion of CD101+ cells and phenotypic profile of these cells found in the SIV model were confirmed in people with HIV on ART. Overall, these data suggest an important role for CD101-expressing CD4 T cells at all stages of HIV/SIV infection and a potential rationale for targeting CD101 to limit HIV pathogenesis and persistence, particularly at mucosal sites.
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Infecções por HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Linfócitos T CD4-Positivos , Infecções por HIV/metabolismo , Humanos , Macaca mulattaRESUMO
The TGF-ß-regulated Chloride Intracellular Channel 4 (CLIC4) is an essential participant in the formation of breast cancer stroma. Here, we used data available from the TCGA and METABRIC datasets to show that CLIC4 expression was higher in breast cancers from younger women and those with early-stage metastatic disease. Elevated CLIC4 predicted poor outcome in breast cancer patients and was linked to the TGF-ß pathway. However, these associations did not reveal the underlying biological contribution of CLIC4 to breast cancer progression. Constitutive ablation of host Clic4 in two murine metastatic breast cancer models nearly eliminated lung metastases without reducing primary tumor weight, while tumor cells ablated of Clic4 retained metastatic capability in wildtype hosts. Thus, CLIC4 was required for host metastatic competence. Pre- and post-metastatic proteomic analysis identified circulating pro-metastatic soluble factors that differed in tumor-bearing CLIC4-deficient and wildtype hosts. Vascular abnormalities and necrosis increased in primary tumors from CLIC4-deficient hosts. Transcriptional profiles of both primary tumors and pre-metastatic lungs of tumor-bearing CLIC4-deficient hosts were consistent with a microenvironment where inflammatory pathways were elevated. Altogether, CLIC4 expression in human breast cancers may serve as a prognostic biomarker; therapeutic targeting of CLIC4 could reduce primary tumor viability and host metastatic competence.
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Neoplasias da Mama , Canais de Cloreto , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Canais de Cloreto/biossíntese , Canais de Cloreto/genética , Feminino , Humanos , Camundongos , Metástase Neoplásica , Proteômica , Fator de Crescimento Transformador beta/metabolismo , Microambiente TumoralRESUMO
Chronic inflammatory diseases occur in a large portion of the population and are associated with a poor diet. Key natural products found in fruits and vegetables may assist in lowering inflammation associated with chronic diseases such as obesity, diabetes, cardiovascular diseases, and cancer. This review seeks to examine the roles of several natural products, resveratrol (RES), quercetin (QUE), curcumin (CUR), piperine (PIP), epigallocatechin gallate (EGCG), and gingerol (GIN), in their ability to attenuate inflammatory markers in specific diseases states. Additionally, we will discuss findings in past and ongoing clinical trials, detail possible phytochemical-drug interactions, and provide a brief resource for researchers and healthcare professionals on natural product and supplement regulation as well as names of databases with information on efficacy, indications, and natural product-drug interactions. As diet and over-the-counter supplement use are modifiable factors and patients are interested in using complementary and alternative therapies, understanding the mechanisms by which natural products have demonstrated efficacy and the types of drugs they interact with and knowing where to find information on herbs and supplements is important for practicing healthcare providers and researchers interested in this field.
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Produtos Biológicos/farmacologia , Inflamação/prevenção & controle , Compostos Fitoquímicos/farmacologia , Biomarcadores/metabolismo , Doença Crônica , Terapias Complementares , Humanos , Inflamação/metabolismoRESUMO
Accurate smartphone-based outdoor localization systems in deep urban canyons are increasingly needed for various IoT applications. As smart cities have developed, building information modeling (BIM) has become widely available. This article, for the first time, presents a semantic Visual Positioning System (VPS) for accurate and robust position estimation in urban canyons where the global navigation satellite system (GNSS) tends to fail. In the offline stage, a material segmented BIM is used to generate segmented images. In the online stage, an image is taken with a smartphone camera that provides textual information about the surrounding environment. The approach utilizes computer vision algorithms to segment between the different types of material class identified in the smartphone image. A semantic VPS method is then used to match the segmented generated images with the segmented smartphone image. Each generated image contains position information in terms of latitude, longitude, altitude, yaw, pitch, and roll. The candidate with the maximum likelihood is regarded as the precise position of the user. The positioning result achieved an accuracy of 2.0 m among high-rise buildings on a street, 5.5 m in a dense foliage environment, and 15.7 m in an alleyway. This represents an improvement in positioning of 45% compared to the current state-of-the-art method. The estimation of yaw achieved accuracy of 2.3°, an eight-fold improvement compared to the smartphone IMU.
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Pedestres , Smartphone , Algoritmos , Cidades , Humanos , SemânticaRESUMO
Ipilimumab with and without anti-Programmed Death 1 (PD-1) improved overall survival (OS) in melanoma. Despite this, the optimal dose and therapeutic mechanism of ipilimumab in patients remains unclear. KEYNOTE-029 and other studies suggest that low-dose ipilimumab with anti-PD1 maintains efficacy while decreasing toxicity, emphasizing T-cell trafficking and reinvigoration as likely mechanisms. See related article by Long et al., p. 5280.
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Melanoma , Humanos , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológicoRESUMO
Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.
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Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , COVID-19/terapia , SARS-CoV-2/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Feminino , Mortalidade Hospitalar , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Glicoproteína da Espícula de Coronavírus/imunologia , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients <65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients <65 years, but data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy.
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Cognitive functions such as attention and working memory are modulated by noradrenaline receptors in the prefrontal cortex (PFC). The frontal eye field (FEF) has been shown to play an important role in visual spatial attention. However, little is known about the underlying circuitry. The aim of this study was to characterize the expression of noradrenaline receptors on different pyramidal neuron and inhibitory interneuron subtypes in macaque FEF. Using immunofluorescence, we found broad expression of noradrenaline receptors across all layers of the FEF. Differences in the expression of different noradrenaline receptors were observed across different inhibitory interneuron subtypes. No significant differences were observed in the expression of noradrenaline receptors across different pyramidal neuron subtypes. However, we found that putative long-range projecting pyramidal neurons expressed all noradrenaline receptor subtypes at a much higher proportion than any of the other neuronal subtypes. Nearly all long-range projecting pyramidal neurons expressed all types of noradrenaline receptor, suggesting that there is no receptor-specific machinery acting on these long-range projecting pyramidal neurons. This pattern of expression among long-range projecting pyramidal neurons suggests a mechanism by which noradrenergic modulation of FEF activity influences attention and working memory.
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3D-mapping-aided (3DMA) global navigation satellite system (GNSS) positioning that improves positioning performance in dense urban areas has been under development in recent years, but it still faces many challenges. This paper details a new algorithm that explores the potential of using building boundaries for positioning and heading estimation. Rather than applying complex simulations to analyze and correct signal reflections by buildings, the approach utilizes a convolutional neural network to differentiate between the sky and building in a sky-pointing fisheye image. A new skymask matching algorithm is then proposed to match the segmented fisheye images with skymasks generated from a 3D building model. Each matched skymask holds a latitude, longitude coordinate and heading angle to determine the precise location of the fisheye image. The results are then compared with the smartphone GNSS and advanced 3DMA GNSS positioning methods. The proposed method provides degree-level heading accuracy, and improved positioning accuracy similar to other advanced 3DMA GNSS positioning methods in a rich urban environment.