Tobacco or human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent different clinical and epidemiologic entities. This study investigated the prevalence of ...HPV-positive and HPV-negative OPSCC in a reference cancer hospital in Brazil and its association with clinical and demographic data, as well as its impact on overall survival.
HPV infection was determined by p16-IHC in pre-treatment formalin-fixed paraffin-embedded samples from all patients with OPSCC diagnosed at Barretos Cancer Hospital between 2008 and 2018. The prevalence of HPV-positive cases and its temporal trend was assessed, and the association of clinical and demographic data with HPV infection and the impact on patient overall survival was evaluated.
A total of 797 patients with OPSCC were included in the study. The prevalence of HPV-associated tumors in the period was 20.6% 95% confidence interval, 17.5-24.0 with a significant trend for increase of HPV-positive cases over the years (annual percentage change = 12.87). In a multivariate analysis, the variables gender, level of education, smoking, tumor sublocation, region of Brazil, and tumor staging had a significant impact in HPV positivity, and a greater overall survival (OS) was observed in HPV-positive patients (5-year OS: 47.9% vs. 22.0%;
= 0.0001).
This study represents the largest cohort of Brazilian patients with OPSCC characterized according to HPV status. We report significant differences in demographics and clinical presentation according to HPV status, and an increasing trend in prevalence for HPV-induced tumors.
These findings can potentially contribute to a better stratification and management of patients as well as assist in prevention strategies.
The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, ...provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.
Following optical excitations’ life span from creation to decay into photons is crucial in understanding materials photophysics. Macroscopically, this is studied using optical techniques, such as ...photoluminescence excitation spectroscopy. However, excitation and emission pathways can vary at nanometer scales, preventing direct access, as no characterization technique has the relevant spatial, spectral, and time resolution. Here, using combined electron spectroscopies, we explore excitations’ creation and decay in two representative optical materials: plasmonic nanoparticles and luminescent two-dimensional layers. The analysis of the energy lost by an exciting electron that is coincident in time with a visible-ultraviolet photon unveils the decay pathways from excitation toward light emission. This is demonstrated for phase-locked (coherent) interactions (localized surface plasmons) and non–phase-locked ones (point defect excited states). The developed cathodoluminescence excitation spectroscopy images energy transfer pathways at the nanometer scale, widening the available toolset to explore nanoscale materials.
Nanosecond temporal electron-based nano-optical coincidence techniques reveals energy transfer pathways
Relative brain sizes in birds can rival those of primates, but large-scale patterns and drivers of avian brain evolution remain elusive. Here, we explore the evolution of the fundamental brain-body ...scaling relationship across the origin and evolution of birds. Using a comprehensive dataset sampling> 2,000 modern birds, fossil birds, and theropod dinosaurs, we infer patterns of brain-body co-variation in deep time. Our study confirms that no significant increase in relative brain size accompanied the trend toward miniaturization or evolution of flight during the theropod-bird transition. Critically, however, theropods and basal birds show weaker integration between brain size and body size, allowing for rapid changes in the brain-body relationship that set the stage for dramatic shifts in early crown birds. We infer that major shifts occurred rapidly in the aftermath of the Cretaceous-Paleogene mass extinction within Neoaves, in which multiple clades achieved higher relative brain sizes because of a reduction in body size. Parrots and corvids achieved the largest brains observed in birds via markedly different patterns. Parrots primarily reduced their body size, whereas corvids increased body and brain size simultaneously (with rates of brain size evolution outpacing rates of body size evolution). Collectively, these patterns suggest that an early adaptive radiation in brain size laid the foundation for subsequent selection and stabilization.
•Dinosaurs and early birds had similar relative brain sizes•Major shifts in brain-body integration occur in the aftermath of the K-Pg extinction•Rates of brain-body evolution are highest in non-avian dinosaurs, early-diverging birds, parrots, and crows•Corvids, like hominins, evolved larger relative brains and bodies simultaneously
Ksepka et al. reconstruct brain-body scaling in a study of >2,000 birds and non-avian dinosaurs. Their results show that avian brain size evolution was profoundly impacted by the K-Pg mass extinction, in the aftermath of which many clades achieved larger relative brain sizes via body size reduction.
Sulfite reductase (SIR) is a key enzyme in higher plants in the assimilatory sulfate reduction pathway. SIR, being exclusively localized in plastids, catalyzes the reduction of sulfite (SO
) to ...sulfide (S
) and is essential for plant life. We characterized transgenic plants leading to co-suppression of the
gene in tobacco (
Samsun NN). Co-suppression resulted in reduced but not completely extinguished expression of
and in a reduction of SIR activity to about 20-50% of the activity in control plants. The reduction of SIR activity caused chlorotic and necrotic phenotypes in tobacco leaves, but with varying phenotype strength even among clones and increasing from young to old leaves. In transgenic plants compared to control plants, metabolite levels upstream of SIR accumulated, such as sulfite, sulfate and thiosulfate. The levels of downstream metabolites were reduced, such as cysteine, glutathione (GSH) and methionine. This metabolic signature resembles a sulfate deprivation phenotype as corroborated by the fact that
-acetylserine (OAS) accumulated. Further, chlorophyll contents, photosynthetic electron transport, and the contents of carbohydrates such as starch, sucrose, fructose, and glucose were reduced. Amino acid compositions were altered in a complex manner due to the reduction of contents of cysteine, and to some extent methionine. Interestingly, sulfide levels remained constant indicating that sulfide homeostasis is crucial for plant performance and survival. Additionally, this allows concluding that sulfide does not act as a signal in this context to control sulfate uptake and assimilation. The accumulation of upstream compounds hints at detoxification mechanisms and, additionally, a control exerted by the downstream metabolites on the sulfate uptake and assimilation system. Co-suppression lines showed increased sensitivity to additionally imposed stresses probably due to the accumulation of reactive compounds because of insufficient detoxification in combination with reduced GSH levels.
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