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The performances of the models and the derived Bayesian estimators were evaluated in the validation set. RESULTS The best limited sampling strategy led to a bias (min, max), root mean square error between observed and modeled interdose areas under the curve in the validation dataset of -11.72% (-31.08%, 5.00%), 14.9% for ITSIM and -2.21% (-23.40%, 30.01%), 12.4% for Pmetrics with three samples collected at 0.33, 2 and 3 hours post dosing. CONCLUSION Population pharmacokinetic models and Bayesian estimators for IV MMF in HCT have been developed and are now available online (https//pharmaco.chu-limoges.fr) for individual dose adjustment based on the interdose area under the curve. © 2020 The British Pharmacological Society.Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections. Published 2020. This article is a U.S. Governmaent work and is in the public domain in the USA.OBJECTIVE This study aimed to investigate the longitudinal association of the combination of poor appetite (PA) and low masticatory function (LMF) with sarcopenia in community-dwelling older adults. METHODS In total, 173 community-dwelling Japanese adults aged ≥ 75 years participated in the 3-year cohort study. Appetite assessment using the Simplified Nutritional Appetite Questionnaire (SNAQ) and masticatory function assessment using spectrophotometric measurement of differences in gum colour before and after masticating colour-changeable chewing gum (ΔE*ab) were performed at baseline. SNAQ score of ≤ 14 was defined as PA. The lowest tertile of ΔE*ab was defined as LMF. Follow-up examinations were administered annually over a 3-year period to determine sarcopenia incidence, which was defined by the criteria proposed by the Asian Working Group for Sarcopenia. Adjusted hazard ratios (HRs) of sarcopenia incidence according to the presence of PA and LMF were calculated using Cox proportional hazards regression models. RESULTS At baseline, 81 participants (46.8%) had neither PA nor LMF, 34 (19.7%) had PA alone, 35 (20.2%) had LMF alone, and 23 (13.3%) had both PA and LMF. On follow-up, 31 participants (17.9%) developed sarcopenia. After adjusting for covariates, the adjusted HR for sarcopenia in participants with both PA and LMF was 4.4 (95% confidence interval = 1.6-12.2) compared with those without PA or LMF. PA or LMF alone was not significantly associated with sarcopenia development. CONCLUSIONS Coexisting PA and LMF increase the risk of sarcopenia development among community-dwelling Japanese adults aged ≥ 75 years. © 2020 John Wiley & Sons Ltd.To maintain cellular homeostasis, the endoplasmic reticulum (ER) necessitates a continuous removal of ER fragments via a selective, receptor-mediated, form of autophagy known as ER-phagy. In this issue of The EMBO Journal, Jiang et al (2020) shed light on how the best characterized autophagy receptor FAM134B mediates ER membrane fragmentation, the earliest event during ER-phagy. They propose a dynamic model for FAM134B protein oligomerization and ER membrane scission, which are driven by CAMK2B-mediated phosphorylation of the receptor and are altered in sensory neuropathy. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.The meeting, which brought together leading scientists and clinicians in the field of leukemia and lymphoma, was held at the new headquarters of the Josep Carreras Leukaemia Research Institute (IJC) in Badalona, Catalonia, Spain, September 19-20, 2019. Its purpose was to highlight the latest advances in our understanding of the molecular mechanisms driving blood cancers, and to discuss how this knowledge can be translated into an improved management of the disease. Special emphasis was placed on the role of genetic and epigenetic heterogeneity, and the exploitation of epigenetic regulation for developing biomarkers and novel treatment approaches. © 2020 The Authors. Hematological Oncology published by John Wiley & Sons, Ltd.Studies on the temperature (T) responses of photosynthesis and leaf hydraulic conductance (Kleaf ) are important to plant gas exchange. In this study, the temperature responses of photosynthesis and Kleaf were studied in Shanyou 63 (Oryza sativa) and Yannong 19 (Triticum aestivum). Leaf water potential (Ψleaf ) was insensitive to T in Shanyou 63, while it significantly decreased with T in Yannong 19. The differential Ψleaf  - T relationship partially accounted for the differing gm -T relationships, where gm was less sensitive to T in Yannong 19 than in Shanyou 63. With different gm -T and Ψleaf -T relationships, the temperature responses of photosynthetic limitations were surprisingly similar between the two lines, and the photosynthetic rate was highly correlated with gm . With the increasing T, Kleaf increased in Shanyou 63 while it decreased in Yannong 19. Sunitinib The different Kleaf -T relationships were related to different Ψleaf -T relationships. When excluding the effects of water viscosity and Ψleaf , Kleaf was insensitive to T in both lines.

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