760 research outputs found

    COVID-19 and lung cancer: risks, mechanisms and treatment interactions.

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    Cases of the 2019 novel coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to rise worldwide. To date, there is no effective treatment. Clinical management is largely symptomatic, with organ support in intensive care for critically ill patients. The first phase I trial to test the efficacy of a vaccine has recently begun, but in the meantime there is an urgent need to decrease the morbidity and mortality of severe cases. It is known that patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments. Therefore, these patients might be at increased risk of pulmonary complications from COVID-19. The SARS-CoV-2 could in some case induce excessive and aberrant non-effective host immune responses that are associated with potentially fatal severe lung injury and patients can develop acute respiratory distress syndrome (ARDS). Cytokine release syndrome and viral ARDS result from uncontrolled severe acute inflammation. Acute lung injury results from inflammatory monocyte and macrophage activation in the pulmonary luminal epithelium which lead to a release of proinflammatory cytokines including interleukin (IL)-6, IL-1 and tumor necrosis factor-Ī±. These cytokines play a crucial role in immune-related pneumonitis, and could represent a promising target when the infiltration is T cell predominant or there are indirect signs of high IL-6-related inflammation, such as elevated C-reactive protein. A monoclonal anti-IL-6 receptor antibody, tocilizumab has been administered in a number of cases in China and Italy. Positive clinical and radiological outcomes have been reported. These early findings have led to an ongoing randomized controlled clinical trial in China and Italy. While data from those trials are eagerly awaited, patients' management will continue to rely for the vast majority on local guidelines. Among many other aspects, this crisis has proven that different specialists must join forces to deliver the best possible care to patients

    Gender-specific aspects of epidemiology, molecular genetics and outcome: lung cancer.

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    Lung cancer remains the leading cause of cancer-related deaths worldwide in women and men. In incidence, lung cancer ranks second, surpassed by breast cancer in women and prostate cancer in men. However, the historical differences in mortality and incidence rate between both sexes have changed in the last years. In the last decades, we have also witnessed an increased number of lung cancer in female never-smokers. These disparities have grown our interest in studying the impact of the gender and sex in the presentation of lung cancer. The aetiology is yet to be fully elucidated, but the data are clear so far: there is a growing divide between lung cancer presentation in women and men that will change our management and study of lung cancer. This article aims to review the sex and gender differences in lung cancer

    Embracing conservation success of recovering humpback whale populations: Evaluating the case for downlisting their conservation status in Australia

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    Optimism and hope in conservation biology are supported by examples of endangered species recovery, such as the population growth observed in humpback whales in several of the world's oceans. In Australia, monitoring data suggest rapid recovery for both east and west coast populations, which are now larger than 50% of their pre-whaling abundance. The measured growth rates exceed known species trends worldwide and have no indication of diminishing. Under Australian Commonwealth legislation and regulations, these populations should be considered for downlisting, as they are not eligible for listing as a threatened species against all statutory criteria. A change in conservation status will produce new challenges for the conservation and management of a recovered species, especially with the Australian economic landscape experiencing large-scale growth and development in recent years. More importantly, a recovered humpback whale population may bring a positive shift in the research goals and objectives throughout Australia by ensuring other endangered species an equal chance of recovery while delivering hope, optimism, and an opportunity to celebrate a conservation success

    Novel targets for immune-checkpoint inhibition in cancer.

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    Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer. We highlight their biology, emphasizing the current understanding of resistance mechanisms and focusing on promising strategies that are under investigation. We also summarize current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients

    Temporal and regional variability in the skin microbiome of humpback whales along the Western Antarctic Peninsula

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    Ā© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Applied and Environmental Microbiology 84 (2018): e02574-17, doi:10.1128/AEM.02574-17.The skin is the first line of defense between an animal and its environment, and disruptions in skin-associated microorganisms can be linked to an animal's health and nutritional state. To better understand the skin microbiome of large whales, high-throughput sequencing of partial small subunit ribosomal RNA genes was used to study the skin-associated bacteria of 89 seemingly healthy humpback whales (Megaptera novaeangliae) sampled along the Western Antarctic Peninsula (WAP) during early (2010) and late (2013) austral summers. Six core genera of bacteria were present in 93% or more of all humpback skin samples. A shift was observed in the average relative abundance of these core genera over time, with the emergence of four additional core genera corresponding to a decrease in water temperature, possibly caused by seasonal or foraging related changes in skin biochemistry that influenced microbial growth, or other temporal-related factors. The skin microbiome differed between whales sampled at several regional locations along the WAP, suggesting that environmental factors or population may also influence the whale skin microbiome. Overall, the skin microbiome of humpback whales appears to provide insight into animal and environmental-related factors and may serve as a useful indicator for animal health or ecosystem alterations.This project was supported by 67 donors to the ā€œWhale Bacterial Buddiesā€ crowdfunded project supported by WHOI, the Edna Bailey Sussman Fund, and the Michael K. Orbach Enrichment Fund awarded to K. C. Bierlich

    The Genetic Structure of Pacific Islanders

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    Human genetic diversity in the Pacific has not been adequately sampled, particularly in Melanesia. As a result, population relationships there have been open to debate. A genome scan of autosomal markers (687 microsatellites and 203 insertions/deletions) on 952 individuals from 41 Pacific populations now provides the basis for understanding the remarkable nature of Melanesian variation, and for a more accurate comparison of these Pacific populations with previously studied groups from other regions. It also shows how textured human population variation can be in particular circumstances. Genetic diversity within individual Pacific populations is shown to be very low, while differentiation among Melanesian groups is high. Melanesian differentiation varies not only between islands, but also by island size and topographical complexity. The greatest distinctions are among the isolated groups in large island interiors, which are also the most internally homogeneous. The pattern loosely tracks language distinctions. Papuan-speaking groups are the most differentiated, and Austronesian or Oceanic-speaking groups, which tend to live along the coastlines, are more intermixed. A small ā€œAustronesianā€ genetic signature (always <20%) was detected in less than half the Melanesian groups that speak Austronesian languages, and is entirely lacking in Papuan-speaking groups. Although the Polynesians are also distinctive, they tend to cluster with Micronesians, Taiwan Aborigines, and East Asians, and not Melanesians. These findings contribute to a resolution to the debates over Polynesian origins and their past interactions with Melanesians. With regard to genetics, the earlier studies had heavily relied on the evidence from single locus mitochondrial DNA or Y chromosome variation. Neither of these provided an unequivocal signal of phylogenetic relations or population intermixture proportions in the Pacific. Our analysis indicates the ancestors of Polynesians moved through Melanesia relatively rapidly and only intermixed to a very modest degree with the indigenous populations there
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