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Chirality is a key factor in the safety and efficacy of many drug products and thus the production of single enantiomers of drug intermediates and drugs has become important and state ...of the art in the pharmaceutical industry. There has been an increasing awareness of the enormous potential of microorganisms and enzymes (biocatalysts) for the transformation of synthetic chemicals with high chemo-, regio- and enatioselectivities providing products in high yields and purity. In this article, biocatalytic processes are described for the synthesis of key chiral intermediates for development pharmaceuticals.
Chest radiograph interpretation is critical for the detection of thoracic diseases, including tuberculosis and lung cancer, which affect millions of people worldwide each year. This time-consuming ...task typically requires expert radiologists to read the images, leading to fatigue-based diagnostic error and lack of diagnostic expertise in areas of the world where radiologists are not available. Recently, deep learning approaches have been able to achieve expert-level performance in medical image interpretation tasks, powered by large network architectures and fueled by the emergence of large labeled datasets. The purpose of this study is to investigate the performance of a deep learning algorithm on the detection of pathologies in chest radiographs compared with practicing radiologists.
We developed CheXNeXt, a convolutional neural network to concurrently detect the presence of 14 different pathologies, including pneumonia, pleural effusion, pulmonary masses, and nodules in frontal-view chest radiographs. CheXNeXt was trained and internally validated on the ChestX-ray8 dataset, with a held-out validation set consisting of 420 images, sampled to contain at least 50 cases of each of the original pathology labels. On this validation set, the majority vote of a panel of 3 board-certified cardiothoracic specialist radiologists served as reference standard. We compared CheXNeXt's discriminative performance on the validation set to the performance of 9 radiologists using the area under the receiver operating characteristic curve (AUC). The radiologists included 6 board-certified radiologists (average experience 12 years, range 4-28 years) and 3 senior radiology residents, from 3 academic institutions. We found that CheXNeXt achieved radiologist-level performance on 11 pathologies and did not achieve radiologist-level performance on 3 pathologies. The radiologists achieved statistically significantly higher AUC performance on cardiomegaly, emphysema, and hiatal hernia, with AUCs of 0.888 (95% confidence interval CI 0.863-0.910), 0.911 (95% CI 0.866-0.947), and 0.985 (95% CI 0.974-0.991), respectively, whereas CheXNeXt's AUCs were 0.831 (95% CI 0.790-0.870), 0.704 (95% CI 0.567-0.833), and 0.851 (95% CI 0.785-0.909), respectively. CheXNeXt performed better than radiologists in detecting atelectasis, with an AUC of 0.862 (95% CI 0.825-0.895), statistically significantly higher than radiologists' AUC of 0.808 (95% CI 0.777-0.838); there were no statistically significant differences in AUCs for the other 10 pathologies. The average time to interpret the 420 images in the validation set was substantially longer for the radiologists (240 minutes) than for CheXNeXt (1.5 minutes). The main limitations of our study are that neither CheXNeXt nor the radiologists were permitted to use patient history or review prior examinations and that evaluation was limited to a dataset from a single institution.
In this study, we developed and validated a deep learning algorithm that classified clinically important abnormalities in chest radiographs at a performance level comparable to practicing radiologists. Once tested prospectively in clinical settings, the algorithm could have the potential to expand patient access to chest radiograph diagnostics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inelastic neutron scattering recently confirmed the theoretical prediction of a ↑↑↓↓-magnetic state along the legs of quasi-one-dimensional iron-based ladders in the orbital-selective Mott phase ...(OSMP). We show here that electron doping of the OSMP induces a whole class of novel block states with a variety of periodicities beyond the previously reported π/2 pattern. We discuss the magnetic phase diagram of the OSMP regime that could be tested by neutrons once appropriate quasi-1D quantum materials with the appropriate dopings are identified.
The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet ...available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding.
For the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries.
The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir–Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein.
In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir–Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.
Nanomedicine is a relatively new field that is rapidly evolving. Formulation of drugs on the nanoscale imparts many physical and biological advantages. Such advantages can in turn translate into ...improved therapeutic efficacy and reduced toxicity. While approximately 50 nanotherapeutics have already entered clinical practice, a greater number of drugs are undergoing clinical investigation for a variety of indications. This review aims to examine all the nanoformulations that are currently undergoing clinical investigation and their outlook for ultimate clinical translation. WIREs Nanomed Nanobiotechnol 2017, 9:e1416. doi: 10.1002/wnan.1416
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Cr-, W-, Mo-, and Cu-doped Co-B catalyst showed 3-4 times increment in H2 generation rate when compared to the undoped catalyst for hydrolysis of NaBH4 at 298K, while Ni and Fe are only able to ...create a marginal increment in the catalytic performance. A systematic and comparative study is conducted on Co-B-based ternary alloy catalysts for H2 generation by hydrolysis of NaBH4 . Various transition metals, namely Ni, Fe, Cu, Cr, Mo, and W, were added to Co-B catalyst by chemical reduction of the corresponding metal salts. All the transition metals in the Co-B compounds behave in a dissimilar manner while influencing the catalytic activity. Cr, W, Mo, and Cu impose significant promoting effects on the Co-B catalyst by increasing the H 2 generation rate by 3-4 times when compared to the undoped catalyst. On the contrary, Ni and Fe are only able to create a marginal increment in the catalytic performance of the Co-B catalyst. The metal/(Co+metal) molar ratio was varied in the catalyst in order to study the effect of metal doping on surface morphology, electronic interaction, and catalytic efficiency of the alloy catalyst. This systematic variation also contributed to clarify the role of each dopant metal in the electron exchange mechanism involved in NaBH 4 hydrolysis. The promoting effects of the dopant metals are mainly discussed in terms of large active surface area, ability to act as Lewis acid sites for better absorption of OH- group, electronic interaction with Co active metal, and amorphous nature of the alloy catalyst. PUBLICATION ABSTRACT
Summary
Remote dermatology consultations largely superseded face‐to‐face (FTF) consultations during the peak of the COVID‐19 pandemic in the UK. Remote examination of patients with hidradenitis ...suppurativa (HS) brings particular challenges, given the propensity of HS to affect intimate body areas. To understand the impact of remote consultations on the care of patients with HS, a retrospective analysis was conducted of all consultations from 2 April to 29 October 2020 at the HS clinic at Imperial College Healthcare NHS Trust. In this group of patients with HS, 46.3% were black, compared with 7.0% of patients attending general dermatology clinics (P < 0.001). The majority (65.9%) of patients had previously received or were currently taking adalimumab. All consultations were performed by telephone and in 50.7% of the consultations, patients were assessed as having unstable (u)HS, with 81.1% of these uHS episodes leading to a change in pharmacological therapy. The decision‐making process was aided by patient‐submitted photographs at only 8.1% of consultations involving uHS, for reasons of patient privacy, comfort and data security. The data suggest that HS is an inherently unstable disease despite maximal medical therapy, and this study highlights important reasons for the assessment of patients with HS by FTF consultations where safely possible.
TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 ...is coexpressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy.
•A unique context-dependent TRP channel regulation by disinhibitory mechanism•Tmem100 as a potentiating modulator of TRPA1 in the TRPA1-TRPV1 complex•Tmem100-mutant-derived cell-permeable peptide as novel pain therapeutics•The first mechanistic study of Tmem100, an important gene implicated in diseases
TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Weng et al. identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Targeting this modulation, they developed a strategy for blocking persistent pain.
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