Gardnermccollum1980

Although chest CT has been widely used in patients with COVID-19, its role for early diagnosis of COVID-19 is unclear. We report the diagnostic performance of chest CT using structured reporting in a routine clinical setting during the early phase of the epidemic in Germany.

Patients with clinical suspicion of COVID-19 and moderate-to-severe symptoms were included in this retrospective study. CTs were performed and reported before RT-PCR results (reference standard) became available. A structured reporting system was used that concluded in a recently described five-grade score ("CO-RADS"), indicating the level of suspicion for pulmonary involvement of COVID-19 from 1 = very low to 5 = very high. Structured reporting was performed by three Radiologists in consensus.

In 96 consecutive patients (50 male, mean age 64), RT-PCR was positive in 20 (21%) cases. CT features significantly more common in RT-PCR-positive patients were ground-glass opacities as dominant feature, crazy paving, hazy margins of opacities, and multifocal bilateral distribution (

< 0.05). Using a cut-off point between CO-RADS 3 and 4, sensitivity was 90%, specificity 91%, positive predictive value 72%, negative predictive value 97%, and accuracy 91%. ROC analysis showed an AUC of 0.938.

Structured reporting of chest CT with a five-grade scale provided accurate diagnosis of COVID-19. Its use was feasible and helpful in clinical routine.

Chest CT with structured reporting may be a provisional diagnostic alternative to RT-PCR testing for early diagnosis of COVID-19, especially when RT-PCR results are delayed or test capacities are limited.

Chest CT with structured reporting may be a provisional diagnostic alternative to RT-PCR testing for early diagnosis of COVID-19, especially when RT-PCR results are delayed or test capacities are limited.Canonical histones (H2A, H2B, H3, and H4) are present in all eukaryotes where they package genomic DNA and participate in numerous cellular processes, such as transcription regulation and DNA repair. In addition to the canonical histones, there are many histone variants, which have different amino acid sequences, possess tissue-specific expression profiles, and function distinctly from the canonical counterparts. A number of histone variants, including both core histones (H2A/H2B/H3/H4) and linker histones (H1/H5), have been identified to date. Htz1 (H2A.Z) and CENP-A (CenH3) are present from yeasts to mammals, and H3.3 is present from Tetrahymena to humans. In addition to the prevalent variants, others like H3.4 (H3t), H2A.Bbd, and TH2B, as well as several H1 variants, are found to be specific to mammals. Among them, H2BFWT, H3.5, H3.X, H3.Y, and H4G are unique to primates (or Hominidae). In this review, we focus on localization and function of primate- or hominidae-specific histone variants.Distributed point charge models (DCM) and their minimal variants (MDCM) have been integrated with tools widely used for condensed-phase simulations, including a virial-based barostat and a slow-growth algorithm for thermodynamic integration. Minimal DCM is further developed in a systematic fashion to reduce fitting errors in the electrostatic interaction energy, and a new fragment-based approach offers considerable speedup of the MDCM fitting process for larger molecules with increased numbers of off-centered charged sites. Finally, polarizable (M)DCM is also introduced in the present work. The developments are used in condensed-phase simulations of popular force fields with commonly applied simulation conditions. (M)DCM equivalents for a range of widely used water force fields and for fluorobenzene (PhF) are developed and applied along with the original models to evaluate the impact of reformulating the electrostatic term. Comparisons of the molecular electrostatic potential (MEP), electrostatic interaction energies, and bulk properties from molecular dynamics simulations for a range of models from simple TIPnP (n = 3-5) to the polarizable, multipolar iAMOEBA models for water and an existing quadrupolar model for PhF confirm that DCMs retain the accuracy of the original models, providing a homogeneous, efficient, and generic point charge alternative to a multipolar electrostatic model for force field development and multilevel simulations.Fluorophores that emit in the near-infrared (NIR, 700-1700 nm) and have high quantum yields are urgently needed for many technical applications such as organic light-emitting diodes or bioimaging. The design of such chromophores is hampered by the energy gap law, which states that shifting the emission to lower wavelengths is accompanied by a dramatic increase in the nonradiative decay rate. In this article we argue that linear oligomers with J-type excitonic coupling are ideal NIR fluorophores because of the advantageous dependence of the emission energy and the radiative and nonradiative rates on the length N over which the excitation is delocalized. The lowering of the emission energy due to exciton splitting and the linear increase of the radiative rate with length (super-radiance) are well understood. However, less attention has been paid to the decrease of the nonradiative rate with length, which can compensate for the exponential increase due to the energy gap law. According to the exciton model, the Huang-Rhys factors decrease like N-2 while the strength of the nonadiabatic coupling remains approximately constant. Plugging these relations into the Englman-Jortner's energy gap law, we show that for excitonic coupling that is not too strong the nonradiative rate decreases quickly with N. This phenomenon explains the decrease of the nonradiative rate with length in J-aggregates of carbocyanine dyes and the exceptionally high fluorescence quantum yields of linear ethyne-linked zinc-porphyrin arrays, which seemed to defy the energy gap law.Multitask deep neural networks learn to predict ligand-target binding by example, yet public pharmacological data sets are sparse, imbalanced, and approximate. We constructed two hold-out benchmarks to approximate temporal and drug-screening test scenarios, whose characteristics differ from a random split of conventional training data sets. We developed a pharmacological data set augmentation procedure, Stochastic Negative Addition (SNA), which randomly assigns untested molecule-target pairs as transient negative examples during training. Under the SNA procedure, drug-screening benchmark performance increases from R2 = 0.1926 ± 0.0186 to 0.4269 ± 0.0272 (122%). This gain was accompanied by a modest decrease in the temporal benchmark (13%). SNA increases in drug-screening performance were consistent for classification and regression tasks and outperformed y-randomized controls. Our results highlight where data and feature uncertainty may be problematic and how leveraging uncertainty into training improves predictions of drug-target relationships.Minimizing the energy difference between the lowest singlet (S1) and the lowest triplet states, ΔEST, is the main strategy to design thermally activated delayed fluorescence (TADF) molecules, and spatially separating the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) is the general method in the design. However, such a separation also tends to reduce the oscillator strength of the S1 state. In real systems, vibrations change the S1 oscillator strength, and thus one needs to consider the vibronic coupling toward searching for TADF candidate molecules. Here, we evaluate the importance of vibronic coupling by including the first-order perturbative correction to the transition dipole moments of carbazolyl-phthalonitrile derivatives. Indeed, some molecules display large enhancements in their oscillator strengths, with their fluorescence lifetimes reduced by 2 orders of magnitude. The twisting mode between the carbazole groups and phthalonitrile is the most important mode in inducing the perturbations. Thus, performing the perturbative correction is crucial in attaining more reliable predictions on their fluorescence propensities. We also observe that some other molecules, whose zeroth-order predicted fluorescence rates are much slower than the actual experimental data, are affected little by the same first-order correction. For these molecules, we deduce that the geometry-dependent excited-state switching kicks in. Our results demonstrate the significance of vibronic coupling in TADF molecules and the importance of adopting correction schemes as the guidelines for screening of useful TADF molecules.Plants from the Solanaceae family are known to be sources of several nutritionally relevant steroidal glycoalkaloids (SGAs). With the aim of quantitatively investigating the occurrence of the main SGA from tomatoes, eggplants, and potatoes in various food samples and evaluating their relevance in the human diet, a rapid single-step extraction liquid chromatography-tandem mass spectrometry method was developed. Over the course of isolating several commercially unavailable SGAs from tomato products to use them as reference standards, a previously unknown derivative was detected, structurally characterized, and identified as a novel isomer of esculeoside B-1 and B-2. Selleck AM1241 After validation of the method, 36 food items exclusively derived from Solanaceae plants were analyzed for their SGA contents and a specific occurrence of each alkaloid in tomato, eggplant, or potato products was revealed. This is the first study reporting quantitative data on the occurrence of esculeoside A, B-1, B-2, and iso-esculeoside B in tomato products obtained by using appropriate reference compounds rather than applying a semi-quantitative approach based on α-tomatine as a reference. Some of the analyzed tomato products contained the esculeosides in concentrations of >500 mg/kg, clearly indicating their relevance in the human diet and the need of investigating their potential bioactivities in the future.Mining the steadily increasing amount of chemical and biological data is a key challenge in drug discovery. Graph databases offer viable alternatives for capturing interrelationships between molecules and for generating novel insights for design. In a graph database, molecules and their properties are mapped to nodes, while relationships are described by edges. Here, we introduce a graph database for navigation in chemical space, analogue searching, and structure-activity relationship (SAR) analysis. We illustrate this concept using hERG channel inhibitors from ChEMBL to extract SAR knowledge. This graph database is built using different relationships, namely 2D-fingerprint similarity, matched molecular pairs, topomer distances, and structure-activity landscape indices (SALI). Typical applications include retrieving analogues linked by single or multiple edge paths to the query compound as well as detection of nonadditive SAR features. Finally, we identify triplets of linked molecules for clustering. The speed of searching and analysis allows the user to interactively navigate the database and to address complex questions in real-time.The conformational behavior of carboxylic acids has attracted considerable attention, as it can be used as a gateway for the study of more complex phenomena. Here, we present an experimental and computational study of pyrrole-2-carboxylic acid (PCA) conformational space and the vibrational characterization of the compound by infrared spectroscopy. link2 The possibility of promoting conformational transformations using selective vibrational excitation of the 2ν(OH) and 2ν(NH) stretching overtones is explored. link3 Two conformers, exhibiting the cis configuration of the COOH group (O═C-O-H dihedral angle near 0°) and differing by the orientation of the carboxylic group with respect to the pyrrole ring (i.e., showing either a cis or a trans NCC═O arrangement), were found to coexist initially for the compound isolated in a cryogenic nitrogen matrix, in an 8614 ratio, and were characterized by infrared spectroscopy. A third conformer, with the COOH group in the trans configuration, was produced, in situ, by narrowband near-infrared (NIR) excitation of the most stable PCA form (with a cis NCC═O moiety).