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Background: Fibroblast activation protein-α (FAPα) is selectively overexpressed in tumor-associated fibroblasts in more than 90% of epithelial tumors, and may be a good target for anticancer treatment, for example, using an anti-FAPα recombinant antibody (rAb) labeled with radionuclides. In the present report, the radiolabeling and preclinical evaluation of novel anti-FAPα rAbs were investigated. Materials and Methods: Two novel anti-FAPα VHHs (AMS002-1 and AMS002-2) with high binding affinity to FAPα were selected from an antibody phage library. The anti-FAPα VHHs were then fused with the Fc fragment of human IgG4 to create two VHH-Fc rAbs. The VHH-Fc rAbs were radiolabeled with ⁸⁹Zr and ¹⁷⁷Lu. The radiolabeled products were evaluated by radioligand-binding assays using FAPα-expressing cells. The biodistribution and tumor-targeting properties were investigated by small-animal PET/CT. AMS002-1-Fc, which showed promising tumor-targeting properties in ⁸⁹Zr-microPET imaging, was radiolabeled with ¹⁷⁷Lu for efficacy study on HT1080 tumor-bearing mice and monitored with SPECT/CT imaging. Results: The two VHH-Fc rAbs with good affinity with K_D values in low nanomolar range were identified. Both PET/CT imaging with ⁸⁹Zr-AMS002-1-Fc rAb and SPECT/CT imaging with ¹⁷⁷Lu-AMS002-1-Fc rAb demonstrated highest tumor uptakes at 72 h p.i. and long tumor retention in the preclinical models. Furthermore, ex vivo biodistribution analysis revealed high tumor uptake of ⁸⁹Zr-AMS002-1-Fc at 48 h p.i. with the value of 6.91% ± 2.08% ID/g. Finally, radioimmunotherapy with ¹⁷⁷Lu-AMS002-1-Fc rAb delayed the tumor growth without significant weight loss in mice with HT1080 xenografts. The tumor size of untreated control group was 2.59 times larger compared with the treatment group with ¹⁷⁷Lu-AMS002-1-Fc at day 29. Conclusion: ⁸⁹Zr/¹⁷⁷Lu-AMS002-1-Fc represent a pair of promising radiopharmaceuticals for theranostics on FAPα-expressing tumors.

Habitat disturbance leads to biodiversity decline and modifications in the landscape structure and composition, affecting both dispersal movements and ecological processes at different temporal and spatial scales. The Ecuadorian Tropical Andes harbour suitable habitats for the distribution of a wide variety of species; however, there is a lack of studies focused on mammal diversity and its association with the habitat attributes in the central-eastern slopes. Here, we reported the diversity of terrestrial mammals recorded between 2019 and 2021 in a camera-trap monitoring study in the Candelaria and Machay reserves in the upper basin of the Pastaza River, Ecuador. We performed site-occupancy probability analysis to assess the influence of spatial variables in the species' occurrence and also, based on natural marks, we reported preliminary findings in Andean bear individual identification. We detected 22 species of terrestrial mammals. Alpha diversity was similar between reserves with slightly higher species richness in Machay. Evenness indices showed unequal species distribution, with the Andean bear and domestic dogs exhibiting greater dominance. In addition, species composition was dissimilar between reserves, where the species turnover mostly explained the beta diversity. We observed that Andean bear and puma detections increased according to the natural vegetation cover. Conversely, domestic dogs were frequently detected in cells with an increasing proportion of pastures and crops. Additionally, we identified 26 Andean bears and six individuals recaptured during our study. Our results caution about the disturbance derived from human activities since we recorded unprecedented detections of domestic dogs in wild habitats. Nonetheless, it highlights the importance of private conservation areas (e.g. Candelaria, Machay and others) for supporting the occurrence and dispersal of terrestrial mammal species between larger areas in the upper basin of the Pastaza River.

This study aims to analyze the asymmetric long-run relationship between economic growth (EG), foreign direct investment (FDI), and carbon emissions (CO₂) within the context of the environmental Kuznets curve (EKC) and the pollution haven hypothesis (PHH) in China. Employing the quarterly data from 1982Q1 to 2018Q4, we have used novel techniques to meet the stated objectives of our study, named quantile ARDL and quantile Granger causality. The study provides novel outcomes using the advanced quantile ARDL and quantile Granger causality tests. The significant implication of this method is that it provides locational asymmetry. We find strong evidence of the EKC and PHH for China based on the empirical results of linear and nonlinear ARDL models. Similarly, findings of quantile Granger causality validate the bidirectional relationship among all variables in upper and lower quantiles. Moreover, the results of the Wald test confirm the asymmetric long-run relationship between FDI and carbon emissions (CO₂). Thus, legal measures must be enhanced, accepted, rigorously imposed, and monitored in all provinces to assure a further reduction in carbon emissions. This study will be conducive for the policymakers to combat environmental contamination concerning economic growth and FDI inflow in China.

Objective: As the Coronavirus disease 2019 (COVID-19) pandemic spread globally, more human immunodeficiency virus (HIV) positive patients began to appear infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the clinical course of HIV and SARS-CoV-2 co-infected patients from a local perspective.

Methods: HIV and SARS-CoV-2 co-infected patients diagnosed between March 2020 to June 2021 at a tertiary hospital in Turkey were analyzed retrospectively.

Results: Thirty HIV and SARS-CoV-2 co-infected patients were included. Five patients were female, 25 were male, and the mean age was 44.5 ±10.2 years. Twenty-three (76.7%) patients were known to be HIV-positive before their admission to the hospital, and seven (23.7%) patients, were detected by screening after the diagnosis of COVID-19. All patients were known to be HIV-positive; they were on antiretroviral therapy (ART) and virologically suppressed. Twenty-seven patients had a mild course. Three patients were hospitalized, and of them, two patients had died. All hospitalized patients were male and were ART-naïve.

Conclusion: HIV infection alone did not increase the severity of the course of COVID-19 and did not increase the mortality in COVID-19.

The human signaling molecules Tie1 and Tie2 receptor tyrosine kinases (RTKs) play important pathophysiological roles in many diseases, including different cancers. The activity of Tie1 is mediated mainly through the downstream angiopoietin-1 (Ang1)-dependent activation of Tie2, rendering both Tie 1 and the Tie1/Tie2/Ang1 axis attractive putative targets for therapeutic intervention. However, the development of inhibitors that target Tie1 and an understanding of their effect on Tie2 and on the Tie1/Tie2/Ang1 axis remain unfulfilled tasks, due, largely, to the facts that Tie1 is an orphan receptor and is difficult to produce and use in the quantities required for immune antibody library screens. In a search for a selective inhibitor of this orphan receptor, we sought to exploit the advantages (e.g., small size that allows binding to hidden epitopes) of non-immune nanobodies and to simultaneously overcome their limitations (i.e., low expression and stability). We thus performed expression, stability, and affinity screens of yeast-surface-displayed naïve and predesigned synthetic (non-immune) nanobody libraries against the Tie1 extracellular domain. The screens yielded a nanobody with high expression and good affinity and specificity for Tie1, thereby yielding preferential binding for Tie1 over Tie2. The stability, selectivity, potency, and therapeutic potential of this synthetic nanobody were profiled using in vitro and cell-based assays. The nanobody triggered Tie1-dependent inhibition of RTK (Tie2, Akt, and Fak) phosphorylation and angiogenesis in endothelial cells, as well as suppression of human glioblastoma cell viability and migration. This study opens the way to developing nanobodies as therapeutics for different cancers associated with Tie1 activation.

In recent decades, the Black-White test score disparity has decreased, while the test score disparity between children of high- versus low-income parents has increased. This study focuses on a comparison that has, to date, fallen between the separate literatures on these diverging trends - Black and White students whose parents have similarly low, middle, or high incomes (i.e., same-income or race-within-income). To do so, I draw on three nationally representative datasets on ninth or tenth graders, covering the period from 1960 to 2009, all of which contain information on students' math test scores. I find that math test score disparities between Black and White students with same-income parents are to Blacks' disadvantage. Although these disparities have decreased since 1960, in 2009, they remain substantively large, statistically significant, and largest between children of the highest income parents. Further, family and school characteristics that scholars commonly use to explain test score disparities by race or by income have accounted for markedly decreasing shares of race-within-income disparities over time. The study integrates the literatures on test score disparities by race and by income with needed attention to race's historical and continued structural influence, net of parental income, on students' educational experiences and test score outcomes.

Hepatitis A, an acute inflammatory liver disease caused by hepatitis A virus (HAV) infection from close contact with infected people, is highly endemic in the Indian subcontinent. Due to poor sanitary conditions, most of the population is exposed to the virus in childhood. At this age, the disease is asymptomatic and provides life-long protection against the disease. Due to rapid socioeconomic development in some areas, however, pockets of the population are reaching adolescence/adulthood without prior exposure to the virus and are thus susceptible to infection. At these ages, infection carries a higher risk of symptomatic disease and complications including mortality. This review of epidemiology and burden of disease studies in the Indian subcontinent, published since 2005, shows increasing evidence of a shift from high to intermediate endemicity in high-income-typically urban-populations. The prevalence of anti-HAV antibodies (previously reported at > 90%) is lower now in adolescents and young adults (e.g., around 80% in Bangladesh and 55% in 5-15 years in India). As a result, HAV is responsible for more acute viral hepatitis predominantly in this age group (e.g., > 15 years: 3.4% in 1999 to 12.3% in 2003 or high socioeconomic status 13-20 years: 27% in 1999 to 62% in 2003), with a greater clinical and economic burden. Numerous outbreaks due to HAV have been reported [e.g., Sri Lanka (2009-2010): > 13,000 affected; Kashmir (2015-2017): 12 outbreaks; Kerala (2012-2016): 84 outbreaks] from water or food contamination. Due to current shifts in endemicity, a growing proportion of the population is no longer exposed in childhood. As the disease remains highly endemic, it also provides a source for more severe disease in susceptible people at an older age and for outbreaks. Well-tolerated and effective vaccines are available and help prevent disease burden and provide long-term protection. These should now be used more widely to protect more patients from the growing disease burden of hepatitis A. FUNDING: GlaxoSmithKline Biologicals SA. Plain language summary available for this article-please see Fig. 1 and the following link: https://doi.org/10.6084/m9.figshare.9963044.Fig. 1Plain Language Summary. Highlights the context of the article, the endemicity shift and the burden of hepatitis A in adolescents and adults and steps to be taken to address the impact of this disease.