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Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.

Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. CC-92480 modulator To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment.

One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson's Chi-Square/Fisher's exact test.

Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40Gy), with individual cases showing exposures as low as 0-2Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ.

ORN diagnosis should only be considered in cases of radiation exposure >40Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure <40Gy in the necrotic site is included. In cases with exposure >40Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used.

40 Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used.Diatoms are a diverse and globally important phytoplankton group, responsible for an estimated 20% of carbon fixation on Earth. They frequently form spatially extensive phytoplankton blooms, responding rapidly to increased availability of nutrients, including phosphorus (P) and nitrogen (N). Although it is well established that diatoms are common first responders to nutrient influxes in aquatic ecosystems, little is known of the sensory mechanisms that they employ for nutrient perception. Here, we show that P-limited diatoms use a Ca2+-dependent signaling pathway, not previously described in eukaryotes, to sense and respond to the critical macronutrient P. We demonstrate that P-Ca2+ signaling is conserved between a representative pennate (Phaeodactylum tricornutum) and centric (Thalassiosira pseudonana) diatom. Moreover, this pathway is ecologically relevant, being sensitive to sub-micromolar concentrations of inorganic phosphate and a range of environmentally abundant P forms. Notably, we show that diatom recovery from P limitation requires rapid and substantial increases in N assimilation and demonstrate that this process is dependent on P-Ca2+ signaling. P-Ca2+ signaling thus governs the capacity of diatoms to rapidly sense and respond to P resupply, mediating fundamental cross-talk between the vital nutrients P and N and maximizing diatom resource competition in regions of pulsed nutrient supply.One function of perceptual systems is to construct and maintain a reliable representation of the environment. A useful strategy intrinsic to modern "Bayesian" theories of perception1-6 is to take advantage of the relative stability of the input and use perceptual history (priors) to predict current perception. This strategy is efficient1-7 but can lead to stimuli being biased toward perceptual history, clearly revealed in a phenomenon known as serial dependence.8-14 However, it is still unclear whether serial dependence biases sensory encoding or only perceptual decisions.15,16 We leveraged on the "surround tilt illusion"-where tilted flanking stimuli strongly bias perceived orientation-to measure its influence on the pattern of serial dependence, which is typically maximal for similar orientations of past and present stimuli.7,10 Maximal serial dependence for a neutral stimulus preceded by an illusory one occurred when the perceived, not the physical, orientations of the two stimuli matched, suggesting that the priors biasing current perception incorporate the effect of the illusion. However, maximal serial dependence of illusory stimuli induced by neutral stimuli occurred when their physical (not perceived) orientations were matched, suggesting that priors interact with incoming sensory signals before they are biased by flanking stimuli. The evidence suggests that priors are high-level constructs incorporating contextual information, which interact directly with early sensory signals, not with highly processed perceptual representations.Honeybees1 and bumblebees2 perform learning flights when leaving a newly discovered flower. During these flights, bees spend a portion of the time turning back to face the flower when they can memorize views of the flower and its surroundings. In honeybees, learning flights become longer when the reward offered by a flower is increased.3 We show here that bumblebees behave in a similar way, and we add that bumblebees face an artificial flower more when the concentration of the sucrose solution that the flower provides is higher. The surprising finding is that a bee's size determines what a bumblebee regards as a "low" or "high" concentration and so affects its learning behavior. The larger bees in a sample of foragers only enhance their flower facing when the sucrose concentration is in the upper range of the flowers that are naturally available to bees.4 In contrast, smaller bees invest the same effort in facing flowers whether the concentration is high or low, but their effort is less than that of larger bees.