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Breast cancer is the most commonly diagnosed malignancy in women, with triple-negative breast cancer (TNBC) accounting for 10–20% of cases. Historically, fewer treatment options have existed for this subtype of breast cancer, with cytotoxic chemotherapy playing a predominant role. This article aims to review the current treatment paradigm for curative-intent TNBC, while also reviewing potential future developments in this landscape. In addition to chemotherapy, recent advances in the understanding of the molecular biology of TNBC have led to promising new studies of targeted and immune checkpoint inhibitor therapies in the curative-intent setting. The appropriate selection of TNBC patient subgroups with a higher likelihood of benefit from treatment is critical to identify the best treatment approach.  相似文献   
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Background: Positive correlations have been reported between wastewater SARS-CoV-2 concentrations and a community’s burden of infection, disease or both. However, previous studies mostly compared wastewater to clinical case counts or nonrepresentative convenience samples, limiting their quantitative potential.Objectives: This study examined whether wastewater SARS-CoV-2 concentrations could provide better estimations for SARS-CoV-2 community prevalence than reported cases of COVID-19. In addition, this study tested whether wastewater-based epidemiology methods could identify neighborhood-level COVID-19 hotspots and SARS-CoV-2 variants.Methods: Community SARS-CoV-2 prevalence was estimated from eight randomized door-to-door nasal swab sampling events in six Oregon communities of disparate size, location, and demography over a 10-month period. Simultaneously, wastewater SARS-CoV-2 concentrations were quantified at each community’s wastewater treatment plant and from 22 Newport, Oregon, neighborhoods. SARS-CoV-2 RNA was sequenced from all positive wastewater and nasal swab samples. Clinically reported case counts were obtained from the Oregon Health Authority.Results: Estimated community SARS-CoV-2 prevalence ranged from 8 to 1,687/10,000 persons. Community wastewater SARS-CoV-2 concentrations ranged from 2.9 to 5.1log10 gene copies per liter. Wastewater SARS-CoV-2 concentrations were more highly correlated (Pearson’s r=0.96; R2=0.91) with community prevalence than were clinically reported cases of COVID-19 (Pearson’s r=0.85; R2=0.73). Monte Carlo simulations indicated that wastewater SARS-CoV-2 concentrations were significantly better than clinically reported cases at estimating prevalence (p<0.05). In addition, wastewater analyses determined neighborhood-level COVID-19 hot spots and identified SARS-CoV-2 variants (B.1 and B.1.399) at the neighborhood and city scales.Discussion: The greater reliability of wastewater SARS-CoV-2 concentrations over clinically reported case counts was likely due to systematic biases that affect reported case counts, including variations in access to testing and underreporting of asymptomatic cases. With these advantages, combined with scalability and low costs, wastewater-based epidemiology can be a key component in public health surveillance of COVID-19 and other communicable infections. https://doi.org/10.1289/EHP10289  相似文献   
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The aim of this study was to investigate the mechanisms involved in the immunomodulatory effects of Morinda citrifolia L. (noni) in vitro and in vivo in mice. In vitro, Tahitian Noni Juice (TNJ) and Noni fruit juice concentrates (NFJC) (1, 5mg/mL) potently activate cannabinoid 2 (CB2), but inhibit cannabinoid 1 (CB1) receptors in a concentration-dependant manner. In vivo, oral administration of TNJ ad libitum for 16 days decreased the production of IL-4, but increased the production of IFN-gamma. These results suggest that noni modulates the immune system via activating of the CB2 receptors, and suppressing of the IL-4, but increasing the production of IFN-gamma cytokines. It may also exert beneficial immunomodulation effects in conditions involving inadequate immune responses.  相似文献   
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