keynote 412 phase iii study of pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma hnscc

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CorE from Myxococcus xanthus Is a Copper-Dependent RNA Polymerase Sigma Factor

The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many proteins involved in copper homeostasis that are differentially regulated by this metal. A σ factor of the ECF (extracytoplasmic function) family, CorE, has been found to regulate the expression of the multicopper oxidase cuoB, the P1B-type ATPases copA and copB, and a gene encoding a protein with a heavy-metal-associated domain. Characterization of CorE has revealed that it requires copper to bind DNA in vitro. Genes regulated by CorE exhibit a characteristic expression profile, with a peak at 2 h after copper addition. Expression rapidly decreases thereafter to basal levels, although the metal is still present in the medium, indicating that the activity of CorE is modulated by a process of activation and inactivation. The use of monovalent and divalent metals to mimic Cu(I) and Cu(II), respectively, and of additives that favor the formation of the two redox states of this metal, has revealed that CorE is activated by Cu(II) and inactivated by Cu(I). The activation/inactivation properties of CorE reside in a Cys-rich domain located at the C terminus of the protein. Point mutations at these residues have allowed the identification of several Cys involved in the activation and inactivation of CorE. Based on these data, along with comparative genomic studies, a new group of ECF σ factors is proposed, which not only clearly differs mechanistically from the other σ factors so far characterized, but also from other metal regulators

A qualitative evaluation of the impact of a palliative care course on preregistration nursing students' practice in Cameroon

Background Current evidence suggests that palliative care education can improve preregistration nursing students’ competencies in palliative care. However, it is not known whether these competencies are translated into students’ practice in the care of patients who are approaching the end of life. This paper seeks to contribute to the palliative care evidence base by examining how nursing students in receipt of education report transfer of learning to practice, and what the barriers and facilitators may be, in a resource-poor country. Methods We utilised focus groups and individual critical incident interviews to explore nursing students’ palliative care learning transfer. Three focus groups, consisting of 23 participants and 10 individual critical incident interviews were conducted with preregistration nursing student who had attended a palliative care course in Cameroon and had experience caring for a patient approaching the end of life. Data was analysed thematically, using the framework approach. Results The results suggest that nursing students in receipt of palliative care education can transfer their learning to practice. Students reported recognizing patients with palliative care needs, providing patients with physical, psychosocial and spiritual support and communicating patient information to the wider care team. They did however perceive some barriers to this transfer which were either related to themselves, qualified nurses, the practice setting or family caregivers and patients. Conclusion The findings from this study suggest that nursing student in receipt of palliative care education can use their learning in practice to provide care to patients and their families approaching the end of life. Nevertheless, these findings need to be treated with some caution given the self-reported nature of the data. Demonstrating the link between preregistration palliative care education and patient care is vital to ensuring that newly acquired knowledge and skills are translated and embedded into clinical practice. This study also has implications for advocating for palliative care policies and adequately preparing clinical placement sites for students’ learning and transfer of learning

Genetic parameters for growth, reproductive and maternal traits in a multibreed meat sheep population

The genetic parameters for growth, reproductive and maternal traits in a multibreed meat sheep population were estimated by applying the Average Information Restricted Maximum Likelihood method to an animal model. Data from a flock supported by the Programa de Melhoramento Genético de Caprinos e Ovinos de Corte (GENECOC) were used. The traits studied included birth weight (BW), weaning weight (WW), slaughter weight (SW), yearling weight (YW), weight gain from birth to weaning (GBW), weight gain from weaning to slaughter (GWS), weight gain from weaning to yearling (GWY), age at first lambing (AFL), lambing interval (LI), gestation length (GL), lambing date (LD - number of days between the start of breeding season and lambing), litter weight at birth (LWB) and litter weight at weaning (LWW). The direct heritabilities were 0.35, 0.81, 0.65, 0.49, 0.20, 0.15 and 0.39 for BW, WW, SW, YW, GBW, GWS and GWY, respectively, and 0.04, 0.06, 0.10, 0.05, 0.15 and 0.11 for AFL, LI, GL, LD, LWB and LWW, respectively. Positive genetic correlations were observed among body weights. In contrast, there was a negative genetic correlation between GBW and GWS (-0.49) and GBW and GWY (-0.56). Positive genetic correlations were observed between AFL and LI, LI and GL, and LWB and LWW. These results indicate a strong maternal influence in this herd and the presence of sufficient genetic variation to allow mass selection for growth traits. Additive effects were of little importance for reproductive traits, and other strategies are necessary to improve the performance of these animals

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Reactive oxygen-derived free radicals are key to the endothelial dysfunction of diabetes.

Vascular complications are an important pathological issue in diabetes that lead to the further functional deterioration of several organs. The balance between endothelium-dependent relaxing factors and endothelium-dependent contracting factors (EDCFs) is crucial in controlling local vascular tone and function under normal conditions. Diabetic endothelial dysfunction is characterized by reduced endothelium-dependent relaxations and/or enhanced endothelium-dependent contractions. Elevated levels of oxygen-derived free radicals are the initial source of endothelial dysfunction in diabetes. Oxygen-derived free radicals not only reduce nitric oxide bioavailability, but also facilitate the production and/or action of EDCFs. Thus, the endothelial balance tips towards vasoconstrictor responses over the course of diabetes. © 2009 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.postprin

Functionalized carboxyl nanoparticles enhance mucus dispersion and hydration

Luminal accumulation of viscous, poorly hydrated, and less transportable mucus has been associated with altered mucus rheology and reduced mucociliary clearance. These symptoms are some of the cardinal clinical manifestations found throughout major respiratory diseases as well as gastrointestinal and digestive disorders. Applications of current mucolytics may yield short-term improvements but are continuously challenged by undesirable side-effects. While nanoparticles (NPs) can interact with mucin polymers, whether functionalized NPs can rectify mucus rheology is unknown. Herein, we report that carboxyl-functionalized NPs (24 nm and 120 nm) dramatically reduced mucin gel size and accelerated mucin matrix hydration rate (diffusivity). Our results suggest that carboxyl-functionalized NPs disperse mucin gels possibly by enhancing network hydration. This report highlights the prospective usages of carboxyl-functionalized NPs as a novel mucus dispersant or mucolytic agent in adjusting mucus rheological properties and improving mucociliary transport to relieve clinical symptoms of patients suffering from relevant diseases

The Effect of Particulate Air Pollution on Emergency Admissions for Myocardial Infarction: A Multicity Case-Crossover Analysis

Recently, attention has focused on whether particulate air pollution is a specific trigger of myocardial infarction (MI). The results of several studies of single locations assessing the effects of ambient particular matter on the risk of MI have been disparate. We used a multicity case-crossover study to examine risk of emergency hospitalization associated with fine particulate matter (PM) with aerodynamic diameter < 10 μm (PM(10)) for > 300,000 MIs during 1985–1999 among elderly residents of 21 U.S. cities. We used time-stratified controls matched on day of the week or on temperature to detect possible residual confounding by weather. Overall, we found a 0.65% [95% confidence interval (CI), 0.3–1.0%] increased risk of hospitalization for MI per 10 μg/m(3) increase in ambient PM(10) concentration. Matching on apparent temperature yielded a 0.64% increase in risk (95% CI, 0.1–1.2%). We found that the effect size for PM(10) doubled for subjects with a previous admission for chronic obstructive pulmonary disease or a secondary diagnosis of pneumonia, although these differences did not achieve statistical significance. There was a weaker indication of a larger effect on males but no evidence of effect modification by age or the other diagnoses. We also found that the shape of the exposure–response relationship between MI hospitalizations and PM(10) is almost linear, but with a steeper slope at levels of PM(10) < 50 μg/m(3). We conclude that increased concentrations of ambient PM(10) are associated with increased risk of MI among the elderly

An Antimicrobial Peptide Regulates Tumor-Associated Macrophage Trafficking via the Chemokine Receptor CCR2, a Model for Tumorigenesis

Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human β-defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown., applying a cross-desensitization strategy of CCR2 and its pharmacological inhibitor (RS102895), respectively, was also carried out. outcome and demonstrates the importance of the innate immune system in the development of tumors