© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The microwave spectra of the natural substance coumarin, a planar aromatic molecule with the specific scent of maibowle, a popular fruit punch served in spring and early summer, were recorded using a molecular jet Fourier transform microwave spectrometer working in the frequency range from 4.0 to 26.5 GHz. The rotational constants and centrifugal distortion constants were determined with high precision, reproducing the spectra to experimental accuracy. The spectra of all singly-substituted 13 C and 18 O isotopologues were observed in their natural abundances to determine the experimental heavy atom substitution r s and semi-experimental equilibrium r e SE structures. The experimental bond lengths and bond angles were compared to those obtained from quantum chemical calculations and those of related molecules reported in the literature with benzene as the prototype. The alternation of the C-C bond lengths to the value of 1.39 Å found for benzene reflects the localization of π electrons in coumarin, where the benzene ring and the lactone-like chain -CH=CH-(C=O)-O- are fused. The large, negative inertial defect of coumarin is consistent with out-of-plane vibrations of the fused rings. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Spin-orbit (SO) heavy-atom on the light-atom (SO-HALA) effect is the largest relativistic effect caused by a heavy atom on its light-atom neighbors, leading, e.g. to unexpected NMR chemical shifts of 1H, 13C, and 15N nuclei, when bonded to a HA. In this study, a combined experimental and theoretical evidence for the SO-HALA effect transmitted through hydrogen bond is presented. Solid-state NMR data for a series of 4-dimethylaminopyridine salts containing I-, Br- and Cl- counter ions were obtained experimentally and by theoretical calculations. A comparison of the experimental chemical shifts with those calculated by a standard DFT methodology without the SO contribution to the chemical shifts revealed a remarkable error of the calculated proton chemical shift of a hydrogen atom that is in close contact with the iodide anion. The addition of the relativistic SO correction in the calculations significantly improves overall agreement with the experiment and confirms the propagation of the SO-HALA effect through hydrogen bond. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.On a comprehensive database with 1,644 datapoints, covering several aspects of main-group as well as of transition metal chemistry, we assess the performance of 60 density functional approximations (DFA), among them 36 double hybrids (DH). All calculations are performed using a Slater type orbital (STO) basis set of triple-ζ (TZ) quality and the highly efficient pair atomic resolution of the identity approach for the exchange- and Coulomb-term of the KS matrix (PARI-K and PARI-J, respectively) and for the evaluation of the MP2 energy correction (PARI-MP2). Employing the quadratic scaling SOS-AO-PARI-MP2 algorithm, DHs based on the spin-opposite-scaled (SOS) MP2 approximation are benchmarked against a database of large molecules. We evaluate the accuracy of STO/PARI calculations for B3LYP as well as for the DH B2GP-PLYP and show that the combined basis set and PARI-error is comparable to the one obtained using the well-known def2-TZVPP Gaussian-type basis set in conjunction with global density fitting. While quadruple-ζ (QZ) calculations are currently not feasible for PARI-MP2 due to numerical issues, we show that, on the TZ level, Jacob’s ladder for classifying DFAs is reproduced. However, while the best DHs are more accurate than the best hybrids, the improvements are less pronounced than the ones commonly found on the QZ level. For conformers of organic molecules and noncovalent interactions where very high accuracy is required for qualitatively correct results, DHs provide only small improvements over hybrids, while they still excel in thermochemistry, kinetics, transition metal chemistry and the description of strained organic systems. © 2020 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.BACKGROUND Sparse information regarding plasma iron concentration in neonatal foals and its utility as an inflammatory marker in this population has been published. OBJECTIVES To determine the physiologic plasma iron concentration in neonatal foals. To assess its utility as an inflammatory marker to predict systemic inflammatory response syndrome (SIRS) and as a prognostic marker. ANIMALS Forty-seven ill neonatal foals admitted to a referral equine hospital were divided in 2 groups based on the SIRS criteria (24 SIRS and 23 non-SIRS). Two control groups of 43 hospital and 135 stud farm healthy neonatal foals were also included. METHODS Observational prospective study. Data were summarized by mean and its 95% confidence interval and absolute frequency and percentage for quantitative andqualitative variables. One-way ANOVA, ANCOVA (group and age effects) and Dunnett as posthoc analysis were used to compare plasma iron concentration among groups. RESULTS Neonatal foals with SIRS did not have had any statistically significant different plasma iron concentrations compared to non-SIRS (P = .56) and stud farm control group (P = .99), 172.8 μg/dL (95% CI; 126.0-219.6), 193.1 μg/dL (139.1-247.2), and 181.8 μg/dL (171.3-192.4), respectively. Plasma iron concentration had a large variability in healthy neonatal foals, and was negatively correlated with age in hospital controls (rho = -0.387) and sick neonatal foals (rho = -0.598) (P less then  .001). CONCLUSIONS AND CLINICAL IMPORTANCE Plasma iron was not a useful marker of SIRS in neonatal foals and was not associated with outcome. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.Telehealth has the potential to improve the efficiency of healthcare while reducing the burden on patients and caregivers. Encounters can be synchronous or asynchronous. When used for care of those with amyotrophic lateral sclerosis (ALS) by individual health care providers or by a multidisciplinary team, synchronous telehealth is feasible, acceptable, may produce outcomes comparable to those of in-person care, and is cost effective. Individuals with ALS who use telehealth tend to have lower physical and respiratory function and to live farther from an ALS clinic than those who exclusively attend in-person clinic visits. Asynchronous telehealth can be used as a substitute full multidisciplinary visits, or for remote monitoring of pulmonary function, gait/falls, and speech. Barriers to implementing telehealth on a wider scale include disparities in access to technology and challenges surrounding medical licensure and billing, but these are being addressed. © 2020 Wiley Periodicals, Inc.Currently, methods for conducting multiple treatment propensity scoring in the presence of high-dimensional covariate spaces that result from „big data” are lacking-the most prominent method relies on inverse probability treatment weighting (IPTW). However, IPTW only utilizes one element of the generalized propensity score (GPS) vector, which can lead to a loss of information and inadequate covariate balance in the presence of multiple treatments. This limitation motivates the development of a novel propensity score method that uses the entire GPS vector to establish a scalar balancing score that, when adjusted for, achieves covariate balance in the presence of potentially high-dimensional covariates. Specifically, the generalized propensity score cumulative distribution function (GPS-CDF) method is introduced. A one-parameter power function fits the CDF of the GPS vector and a resulting scalar balancing score is used for matching and/or stratification. Simulation results show superior performance of the new method compared to IPTW both in achieving covariate balance and estimating average treatment effects in the presence of multiple treatments. The proposed approach is applied to a study derived from electronic medical records to determine the causal relationship between three different vasopressors and mortality in patients with non-traumatic aneurysmal subarachnoid hemorrhage. Results suggest that the GPS-CDF method performs well when applied to large observational studies with multiple treatments that have large covariate spaces. © 2020 John Wiley & Sons, Ltd.Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause that is characterized by progressive fibrotic lung remodeling. An abnormal emergence of airway epithelial-like cells within the alveolar compartments of the lung, herein termed bronchiolization, is often observed in IPF. However, the origin of this dysfunctional distal lung epithelium remains unknown due to a lack of suitable human model systems. In this study, we established a human induced pluripotent stem cell (iPSC)-derived air-liquid interface (ALI) model of alveolar epithelial type II (ATII)-like cell differentiation that allows us to investigate alveolar epithelial progenitor cell differentiation in vitro. We treated this system with an IPF-relevant cocktail (IPF-RC) to mimic the pro-fibrotic cytokine milieu present in IPF lungs. Stimulation with IPF-RC during differentiation increases secretion of IPF biomarkers and RNA sequencing (RNA-seq) of these cultures reveals significant overlap with human IPF patient data. IPF-RC treatment further impairs ATII differentiation by driving a shift toward an airway epithelial-like expression signature, providing evidence that a pro-fibrotic cytokine environment can influence the proximo-distal differentiation pattern of human lung epithelial cells. In conclusion, we show for the first time, the establishment of a human model system that recapitulates aspects of IPF-associated bronchiolization of the lung epithelium in vitro. © 2020 Boehringer Ingelheim Pharma GmbH & Co. KG. The FASEB journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.Nearly 6 million Americans suffer from heart failure. Increased fibrosis contributes to functional decline of the heart that leads to heart failure. Previously, we identified a mechanosensitive protein, small proline-rich repeat 3 (SPRR3), in vascular smooth muscle cells of atheromas. In this study, we demonstrate SPRR3 expression in cardiac fibroblasts which is induced in activated fibroblasts following pressure-induced heart failure. Sprr3 deletion in mice showed preserved cardiac function and reduced interstitial fibrosis in vivo and reduced fibroblast proliferation and collagen expression in vitro. SPRR3 loss resulted in reduced activation of Akt, FAK, ERK, and p38 signaling pathways, which are coordinately regulated by integrins and growth factors. SPRR3 deletion did not impede integrin-associated functions including cell adhesion, migration, or contraction. SPRR3 loss resulted in reduced activation of PDGFRβ in fibroblasts. This was not due to the reduced PDGFRβ expression levels or decreased binding of the PDGF ligand to PDGFRβ. SPRR3 facilitated the association of integrin β1 with PDGFRβ and subsequently fibroblast proliferation, suggesting a role in PDGFRβ-Integrin synergy. We postulate that SPRR3 may function as a conduit for the coordinated activation of PDGFRβ by integrin β1, leading to augmentation of fibroblast proliferation and matrix synthesis downstream of biomechanical and growth factor signals. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.