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Since the start of the COVID-19 pandemic, in a short span of 3 years, vaccination against SARS-CoV-2 has resulted in the end of the pandemic. Patients with inborn errors of immunity (IEI) are at an increased risk for SARS-CoV-2 infection; however, serious illnesses and mortality, especially in primary antibody deficiencies (PADs), have been lower than expected and lower than other high-risk groups. This suggests that PAD patients may mount a reasonable effective response to the SARS-CoV-2 vaccine. Several studies have been published regarding antibody responses, with contradictory reports. The current study is, perhaps, the most comprehensive study of phenotypically defined various lymphocyte populations in PAD patients following the SARS-CoV-2 vaccine. In this study, we examined, following two vaccinations and, in a few cases, prior to and following the 1st and 2nd vaccinations, subsets of CD4 and CD8 T cells (Naïve, TCM, TEM, TEMRA), T follicular helper cells (TFH1, TFH2, TFH17, TFH1/17), B cells (naïve, transitional, marginal zone, germinal center, IgM memory, switched memory, plasmablasts, CD21low), regulatory lymphocytes (CD4Treg, CD8Treg, TFR, Breg), and SARS-CoV-2-specific activation of CD4 T cells and CD8 T cells (CD69, CD137), SARS-CoV-2 tetramer-positive CD8 T cells, and CD8 CTL. Our data show significant alterations in various B cell subsets including Breg, whereas only a few subsets of various T cells revealed alterations. These data suggest that large proportions of PAD patients may mount significant responses to the vaccine.
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Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.
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Microambiente Tumoral , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Humanos , Microambiente Tumoral/imunologia , Masculino , Células Matadoras Naturais/imunologia , Feminino , Linfócitos T CD8-Positivos/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Análise de Célula Única/métodos , Células Dendríticas/imunologia , Pessoa de Meia-Idade , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , RNA-Seq , Análise da Expressão Gênica de Célula ÚnicaRESUMO
NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors. Rather, TME-specific TGF-ß and metabolic perturbations such as hypoxia directly suppressed NK cell function. Specifically, an oxygen-dependent reduction in signaling through SLAMF6 was mechanistically responsible for poor NK cell function, as tumor-infiltrating NK cells cultured ex vivo under normoxic conditions exhibited complete restoration of function, while deletion of SLAMF6 abrogated NK cell cytolytic function even under normoxic conditions. Collectively, this work highlights the role of tissue-specific factors in dictating NK cell function, and implicates SLAMF6 signaling as a rational target for immuno-modulation to improve NK cell function in bladder cancer.
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Interactions within the tumor microenvironment (TME) significantly influence tumor progression and treatment responses. While single-cell RNA sequencing (scRNA-seq) and spatial genomics facilitate TME exploration, many clinical cohorts are assessed at the bulk tissue level. Integrating scRNA-seq and bulk tissue RNA-seq data through computational deconvolution is essential for obtaining clinically relevant insights. Our method, ProM, enables the examination of major and minor cell types. Through evaluation against existing methods using paired single-cell and bulk RNA sequencing of human urothelial cancer (UC) samples, ProM demonstrates superiority. Application to UC cohorts treated with immune checkpoint inhibitors reveals pre-treatment cellular features associated with poor outcomes, such as elevated SPP1 expression in macrophage/monocytes (MM). Our deconvolution method and paired single-cell and bulk tissue RNA-seq dataset contribute novel insights into TME heterogeneity and resistance to immune checkpoint blockade.
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BACKGROUND: Advancing age is a major risk factor for respiratory viral infections. The infections are often prolonged and difficult to resolve resulting hospitalizations and mortality. The recent COVID-19 pandemic has highlighted this as elderly subjects have emerged as vulnerable populations that display increased susceptibility and severity to SARS-CoV-2. There is an urgent need to identify the probable mechanisms underlying this to protect against future outbreaks of such nature. Innate immunity is the first line of defense against viruses and its decline impacts downstream immune responses. This is because dendritic cells (DCs) and macrophages are key cellular elements of the innate immune system that can sense and respond to viruses by producing inflammatory mediators and priming CD4 and CD8 T-cell responses. RESULTS: We investigated the changes in innate immune responses to SARS-CoV-2 as a function of age. Our results using human PBMCs from aged, middle-aged, and young subjects indicate that the activation of DCs and monocytes in response to SARS-CoV-2 is compromised with age. The impairment is most apparent in pDCs where both aged and middle-aged display reduced responses. The secretion of IL-29 that confers protection against respiratory viruses is also decreased in both aged and middle-aged subjects. In contrast, inflammatory mediators associated with severe COVID-19 including CXCL-8, TREM-1 are increased with age. This is also apparent in the gene expression data where pathways related host defense display an age dependent decrease with a concomitant increase in inflammatory pathways. Not only are the inflammatory pathways and mediators increased after stimulation with SARS-CoV-2 but also at homeostasis. In keeping with reduced DC activation, the induction of cytotoxic CD8 T cells is also impaired in aged subjects. However, the CD8 T cells from aged subjects display increased baseline activation in accordance with the enhanced baseline inflammation. CONCLUSIONS: Our results demonstrate a decline in protective anti-viral immune responses and increase in damaging inflammatory responses with age indicating that dysregulated innate immune responses play a significant role in the increased susceptibility of aged subjects to COVID-19. Furthermore, the dysregulation in immune responses develops early on as middle-aged demonstrate several of these changes.
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BACKGROUND: Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care. METHODS: Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons. RESULTS: The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories. CONCLUSIONS: The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.
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Clínica Dirigida por Estudantes , Estudantes de Medicina , Humanos , Feminino , Idoso , Estados Unidos , Pessoa de Meia-Idade , Masculino , Medicare , Instituições de Assistência Ambulatorial , Avaliação de Resultados em Cuidados de SaúdeRESUMO
The cuneiform nucleus (CnF) regulates locomotor activity, which is canonically viewed as being primarily involved in initiating locomotion and regulating speed. Recent research shows greater context dependency in the locomotor functions of this nucleus. Glutamatergic neurons, which contain vesicular glutamate transporter 2 (vGLUT2), regulate context-dependent locomotor speed in the CnF and play a role in defensive behavior. Here, we identify projections from the medial zona incerta (mZI) to CnF vGLUT2 neurons that promote exploratory behavior. Using fiber photometry recordings in male mice, we find that mZI gamma-aminobutyric acid (GABA) neurons increase activity during periods of exploration. Activation of mZI GABAergic neurons is associated with reduced spiking of CnF neurons. Additionally, activating both retrogradely labeled mZI-CnF GABAergic projection neurons and their terminals in the CnF increase exploratory behavior. Inhibiting CnF vGLUT2 neuronal activity also increases exploratory behavior. These findings provide evidence for the context-dependent dynamic regulation of CnF vGLUT2 neurons, with the mZI-CnF circuit shaping exploratory behavior.
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Zona Incerta , Camundongos , Animais , Masculino , Zona Incerta/metabolismo , Comportamento Exploratório , Neurônios GABAérgicos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Locomoção , Proteína Vesicular 2 de Transporte de Glutamato/metabolismoRESUMO
PURPOSE: Congenital heart disease affects thousands of newborns each year in the United States. Previous United States-based research has explored how sociodemographic factors may impact health outcomes in infants with congenital heart disease; however, their impact on the incidence of congenital heart disease is unclear. We explored the sociodemographic profile related to congenital heart disease to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with congenital heart disease will encourage implementation of potential preventative measures. DESIGN AND METHODS: We conducted a secondary analysis of longitudinally collected data comparing 39 infants with congenital heart disease and 30 healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with congenital heart disease and healthy controls. RESULTS: We found a statistically significant difference in maternal education between our 2 groups of infants (p = 0.004). CONCLUSION: Maternal education was associated with congenital heart disease. Future studies are needed to further characterize sociodemographic factors that may predict and impact the incidence of congenital heart disease and to determine possible interventions that may help decrease health disparities regarding the incidence of congenital heart disease. PRACTICE IMPLICATIONS: Understanding the associations between maternal sociodemographic factors and infant congenital heart disease would allow clinicians to identify mothers at higher risk of having an infant with congenital heart disease.
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Cardiopatias Congênitas , Lactente , Feminino , Recém-Nascido , Humanos , Estados Unidos/epidemiologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Mães , Escolaridade , Inquéritos e Questionários , IncidênciaRESUMO
Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53-/- and IG10 murine HGSC models. Increasing miR-146a expression in tumors improved anti-tumor immune responses by decreasing immune suppressive neutrophils and increasing CTL infiltration. Mechanistically, miR-146a targets IL-1 receptor-associated kinase 1 and tumor necrosis factor receptor-associated factor 6 adaptor molecules of the transcription factor nuclear factor κB signaling pathway in ID8-p53-/- cells and decreases production of the downstream neutrophil chemoattractant, C-X-C motif chemokine ligand 1. In addition to HGSC, tumoral miR-146a expression also correlates strongly with CTL infiltration in other cancer types including thyroid, prostate, breast, and adrenocortical cancers. Altogether, our findings highlight the ability of miR-146a to overcome immune suppression and improve CTL infiltration in tumors.
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Polyunsaturated fatty acids (PUFAs) have been extensively studied for their health benefits because they can be oxidized by lipoxygenases to form bioactive oxylipins. In this study, we investigated the impact of double bond placement on the kinetic properties and product profiles of human platelet 12-lipoxygenase (h12-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), and human endothelial 15-lipoxygenase-2 (h15-LOX-2) by using 22-carbon (C22) fatty acid substrates with differing double bond content. With respect to kcat/KM values, the loss of Δ4 and Δ19 led to an 18-fold loss of kinetic activity for h12-LOX, no change in kinetic capability for h15-LOX-1, but a 24-fold loss for h15-LOX-2 for both C22-FAs. With respect to the product profiles, h12-LOX produced mainly 14-oxylipins. For h15-LOX-1, the 14-oxylipin production increased with the loss of either Δ4 and Δ19, however, the 17-oxylipin became the major species upon loss of both Δ4 and Δ19. h15-LOX-2 produced mostly the 17-oxylipin products throughout the fatty acid series. This study also investigated the effects of various 17-oxylipins on platelet activation. The results revealed that both 17(S)-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-DHA (17-HDHA) and 17-hydroxy-4Z,7Z,10Z,13Z,15E-DPAn6 (17-HDPAn6) demonstrated anti-aggregation properties with thrombin or collagen stimulation. 17-hydroxy-7Z,10Z,13Z,15E,19Z-DPAn3 (17-HDPAn3) exhibited agonistic properties, and 17-hydroxy-7Z,10Z,13Z,15E-DTA (17-HDTA) showed biphasic effects, inhibiting collagen-induced aggregation at lower concentrationsbut promoting aggregation at higher concentrations. Both 17-hydroxy-13Z,15E,19Z-DTrA (17-HDTrA), and 17-hydroxy-13Z,15E-DDiA (17-HDDiA) induced platelet aggregation. In summary, the number and placement of the double bonds affect platelet activation, with the general trend being that more double bonds generally inhibit aggregation, while less double bonds promote aggregation. These findings provide insights into the potential role of specific fatty acids and their metabolizing LOX isozymes with respect to cardiovascular health.
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Ácidos Graxos , Oxilipinas , Humanos , Araquidonato 15-Lipoxigenase , Isoenzimas , Colágeno , Receptores Depuradores Classe ERESUMO
Phenomenon: Student-run free clinics (SRFCs) serve an integral role in most United States (US) medical schools and contribute substantially to literature on the quality of care to uninsured persons. There has been substantial growth over the past decade of scholarly work produced by SRFCs as they have increased in size and number. Research on patient care outcomes informs better care structures for patients, however there is no current synthesis of patient care outcomes research among SRFCs. This article provides an overview of SRFC research on patient outcomes to understand current research domains and to identify gaps in the literature. Approach: We completed a scoping review by searching Scopus, PubMed, and Journal of Student Run Clinics in June 2021. All peer-reviewed, English-language articles focused on patient-centered outcomes at SRFCs in the US were included. Two independent reviewers performed title, abstract, and full-text screening of relevant works, and eight reviewers conducted data extraction. Descriptive data analysis was performed along with relevant content analysis of patient-centered outcomes. Findings: The search strategy identified 784 studies, of which 87 met inclusion criteria. Most studies were published within the last six years (81.6%), located in California, New York, or Florida (43.7%), and intervention based (33.3%). Many studies (46.0%) had a specific disease of focus of which diabetes was the most researched(19.5%). Patient-centered studies were the leading focus of the study aims (40.2%), where key findings demonstrated primarily improved outcomes in clinic metrics post-intervention (36.8%) or equivalent/better clinical performance than national metrics (20.7%). Insights: This review brings to light gaps in the literature reporting research in SRFCs and can be applied to other low-resource settings. Future efforts to expand SRFC outcomes research should focus on community relationship building, understanding institutional support, and ensuring education on best practices for research within SRFCs. Doing so informs patient care improvement as SRFCs continue to operate as safety net clinics for marginalized populations.
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Objective: To identify perceptions of cannabis use and risk among maternal health providers who provide care for people who use cannabis during pregnancy in safety-net health settings. Methods: Using qualitative, constructivist ground theory methods, we conducted semistructured remote interviews with 10 providers (2 midwives, 6 OB/GYN physicians, and 2 OB/GYN residents) in Southern California, United States, between March 15, 2022, and April 6, 2022. We selected participants through selective sampling using a convenience sample and snowball approach. Providers were eligible for the study if they self-reported via survey to being a maternal health provider (e.g., physician, doula, midwife, and so on) providing care in a safety-net health setting and had cared for people who used cannabis during pregnancy in the last year. Analysis drew upon grounded theory methods to document the socio-structural contexts that contribute to provider perceptions about cannabis. This study was approved by the University of Southern California Institutional Review Board (UP-21-00282-AM009). Results: We identified three categories of provider perceptions of cannabis use and risk during pregnancy: (1) Relying on self-education, (2) Taking a case-by-case approach, and (3) Avoiding cannabis discussions to maintain an alliance with patients. Findings indicate that provider reluctance to counsel patients about cannabis in favor of preserving a therapeutic relationship can overlook the lack of resources and access to health care alternatives available to low-income patients that can shape self-medicating. Conclusions: Nonpunitive policies and training on cannabis use are critical steps for supporting providers to counsel patients who use cannabis during pregnancy, alongside a harm reduction approach that acknowledges the broader socio-structural contexts and barriers facing patients who disclose use.
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Lipid metabolism is a complex process crucial for energy production resulting in high levels of acyl-coenzyme A (acyl-CoA) molecules in the cell. Acyl-CoAs have also been implicated in inflammation, which could be possibly linked to lipoxygenase (LOX) biochemistry by the observation that an acyl-CoA was bound to human platelet 12-lipoxygenase via cryo-EM. Given that LOX isozymes play a pivotal role in inflammation, a more thorough investigation of the inhibitory effects of acyl-CoAs on lipoxygenase isozymes was judged to be warranted. Subsequently, it was determined that C18 acyl-CoA derivatives were the most potent against h12-LOX, human reticulocyte 15-LOX-1 (h15-LOX-1), and human endothelial 15-LOX-2 (h15-LOX-2), while C16 acyl-CoAs were more potent against human 5-LOX. Specifically, oleoyl-CoA (18:1) was most potent against h12-LOX (IC50 = 32 µM) and h15-LOX-2 (IC50 = 0.62 µM), stearoyl-CoA against h15-LOX-1 (IC50 = 4.2 µM), and palmitoleoyl-CoA against h5-LOX (IC50 = 2.0 µM). The inhibition of h15-LOX-2 by oleoyl-CoA was further determined to be allosteric inhibition with a Ki of 82 +/- 70 nM, an α of 3.2 +/- 1, a ß of 0.30 +/- 0.07, and a ß/α = 0.09. Interestingly, linoleoyl-CoA (18:2) was a weak inhibitor against h5-LOX, h12-LOX, and h15-LOX-1 but a rapid substrate for h15-LOX-1, with comparable kinetic rates to free linoleic acid (kcat = 7.5 +/- 0.4 s-1, kcat/KM = 0.62 +/- 0.1 µM-1s-1). Additionally, it was determined that methylated fatty acids were not substrates but rather weak inhibitors. These findings imply a greater role for acyl-CoAs in the regulation of LOX activity in the cell, either through inhibition of novel oxylipin species or as a novel source of oxylipin-CoAs.
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Isoenzimas , Lipoxigenase , Humanos , Oxilipinas , Acil Coenzima A/metabolismo , Inflamação , Receptores Depuradores Classe ERESUMO
This study aimed to assess whether the Teslasuit, a wearable motion-sensing technology, could detect subtle changes in gait following slip perturbations comparable to an infrared motion capture system. A total of 12 participants wore Teslasuits equipped with inertial measurement units (IMUs) and reflective markers. The experiments were conducted using the Motek GRAIL system, which allowed for accurate timing of slip perturbations during heel strikes. The data from Teslasuit and camera systems were analyzed using statistical parameter mapping (SPM) to compare gait patterns from the two systems and before and after slip. We found significant changes in ankle angles and moments before and after slip perturbations. We also found that step width significantly increased after slip perturbations (p = 0.03) and total double support time significantly decreased after slip (p = 0.01). However, we found that initial double support time significantly increased after slip (p = 0.01). However, there were no significant differences observed between the Teslasuit and motion capture systems in terms of kinematic curves for ankle, knee, and hip movements. The Teslasuit showed promise as an alternative to camera-based motion capture systems for assessing ankle, knee, and hip kinematics during slips. However, some limitations were noted, including kinematics magnitude differences between the two systems. The findings of this study contribute to the understanding of gait adaptations due to sequential slips and potential use of Teslasuit for fall prevention strategies, such as perturbation training.
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Marcha , Caminhada , Humanos , Adulto Jovem , Fenômenos Biomecânicos , Extremidade Inferior , Articulação do TornozeloRESUMO
Human 12-lipoxygenase (12-LOX) is a key enzyme involved in platelet activation, and the regulation of its activity has been targeted for the treatment of heparin-induced thrombocytopenia. Despite the clinical importance of 12-LOX, the exact mechanisms by which it affects platelet activation are not fully understood, and the lack of structural information has limited drug discovery efforts. In this study, we used single-particle cryo-electron microscopy to determine high-resolution structures (1.7-2.8 Å) of human 12-LOX. Our results showed that 12-LOX can exist in multiple oligomeric states, from monomer to hexamer, which may affect its catalytic activity and membrane association. We also identified different conformations within the 12-LOX dimer, which likely represent different time points in its catalytic cycle. Furthermore, we identified small molecules bound to 12-LOX. The active site of the 12-LOX tetramer was occupied by an endogenous 12-LOX inhibitor, a long-chain acyl coenzyme A. In addition, we found that the 12-LOX hexamer can simultaneously bind to arachidonic acid and ML355, a selective 12-LOX inhibitor that has passed a phase 1 clinical trial for the treatment of heparin-induced thrombocytopenia and received a fast-track designation by the Food and Drug Administration. Overall, our findings provide novel insights into the assembly of 12-LOX oligomers, their catalytic mechanism, and small molecule binding, paving the way for further drug development targeting the 12-LOX enzyme.
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Ativação Plaquetária , Trombocitopenia , Estados Unidos , Humanos , Microscopia Crioeletrônica , Ácido Araquidônico/metabolismo , Araquidonato 12-Lipoxigenase/metabolismoRESUMO
Type 1 conventional dendritic cells (cDC1s) are critical for CD8+ T cell-mediated tumor control. In this issue of Immunity, Bayerl et al.1 expose a mechanism leading to cancer progression where prostaglandin E2 induces dysfunctional cDC1s, which cannot coordinate CD8+ T cell migration and expansion.
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Dinoprostona , Neoplasias , Humanos , Linfócitos T CD8-Positivos , Movimento Celular , Células DendríticasRESUMO
The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, the basic batch mode of manufacturing vectored vaccines does not allow one to cost-effectively meet the global demand for billions of doses per year. To date, the exposure of humans to VSV infection has been limited. Therefore, a recombinant vesicular stomatitis virus (rVSV), which expresses the spike protein of SARS-CoV-2, was selected as the vector. To determine the operating upstream process conditions for the most effective production of an rVSV-SARS-CoV-2 candidate vaccine, a set of critical process parameters was evaluated in an Ambr 250 modular system, whereas in the downstream process, a streamlined process that included DNase treatment, clarification, and a membrane-based anion exchange chromatography was developed. The design of the experiment was performed with the aim to obtain the optimal conditions for the chromatography step. Additionally, a continuous mode manufacturing process integrating upstream and downstream steps was evaluated. rVSV-SARS-CoV-2 was continuously harvested from the perfusion bioreactor and purified by membrane chromatography in three columns that were operated sequentially under a counter-current mode. Compared with the batch mode, the continuous mode of operation had a 2.55-fold increase in space-time yield and a reduction in the processing time by half. The integrated continuous manufacturing process provides a reference for the efficient production of other viral vectored vaccines.
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Whole-genome sequencing can be used to better understand and assess the functional abilities of microorganisms isolated from spacecraft hardware and associated surfaces for planetary protection (PP) purposes. We sequenced 191 isolates from 6 spaceflight missions with PP requirements and identified them using Illumina-based sequencing methods and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry.
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Background: Congenital heart disease (CHD) affects thousands of newborns each year in the United States (US). Infants born with CHD have an increased risk of adverse health outcomes compared to healthy infants. These outcomes include, but are not limited to, neurodevelopmental, surgical, and mortality-related outcomes. Previous US-based research has explored how sociodemographic factors may impact these health outcomes in infants with CHD; however, their impact on the risk of CHD is unclear. This study aims to explore the sociodemographic profile related to CHD to help address health disparities that arise from race and social determinants of health. Defining the sociodemographic factors associated with CHD will encourage policy change and the implementation of preventative measures. Methods: This study is a secondary analysis of longitudinally collected data. We compared infants with CHD and healthy controls. We used a questionnaire to collect sociodemographic data. Pearson's chi-square test/Fisher's exact tests analyzed the associations among different sociodemographic factors between infants with CHD and healthy controls. Results: We obtained sociodemographic factors from 30 healthy control infants and 39 infants with CHD. We found a statistically significant difference in maternal education between our 2 groups of infants (p=0.004). Conclusion: Maternal education is associated with CHD. Future studies are needed to further characterize sociodemographic factors that may predict and impact the risk of CHD and to determine possible interventions that may help decrease health disparities regarding the risk of CHD.