Russellcarney3302

Introduction Deep discriminative and generative neural-network models are becoming an integral part of the modern approach to ligand-based novel drug discovery. The variety of different architectures of neural networks, the methods of their training, and the procedures of generating new molecules require expert knowledge to choose the most suitable approach.Areas covered Three different approaches to deep learning use in ligand-based drug discovery are considered virtual screening, neural generative models, and mutation-based structure generation. Several architectures of neural networks for building either discriminative or generative models are considered in this paper, including deep multilayer neural networks, different kinds of convolutional neural networks, recurrent neural networks, and several types of autoencoders. Several kinds of learning frameworks are also considered, including adversarial learning and reinforcement learning. Different types of representations for generating molecules, including SMILES, graphs, and several alternative string representations are also considered.Expert opinion Two kinds of problem should be solved in order to make the models built using deep neural networks, especially generative models, a valuable option in ligand-based drug discovery the issue of interpretability and explainability of deep-learning models and the issue of synthetic accessibility of novel compounds designed by deep-learning algorithms.Background Chronic obstructive pulmonary disease (COPD) is one of the diseases that leads to a higher number of hospitalizations in internal medicine departments. These patients are usually older and have greater multimorbidity than COPD patients hospitalized in other departments, which hinders the implementation of clinical guidelines necessarily focused on the management of a single disease.Aims To ascertain the opinion of Spanish internists on the management of COPD in scenarios in which the available evidence is sparse and to produce a consensus document designed to assist in decision-making in COPD patients with comorbidities treated in internal medicine services.Methods After identifying the clinical areas of greatest uncertainty by consensus, a survey was designed with 89 questions on the epidemiology and diagnosis of COPD, its management both in stable phase and during decompensation, and the treatment of the associated comorbidities in outpatients and inpatients. The consensus process was carried out using the Delphi method in an anonymized two-round process.Results The survey was completed by 67 internists experienced in the clinical management of COPD. Of all the questions posed, a consensus was reached for 51 (57.3%) in the first round and for 67 (75.3%) in the second round. Tacrolimus The result of the process is a series of 67 suggestions that may assist in the care of these patients.Conclusions Our study allows us to ascertain the views of a large number of internists experienced in the management of COPD and to learn how the recommendations for guidelines are applied in clinical practice.To evaluate the change in the position of intrastromal corneal ring segments (ICRS) implanted in keratoconus patients within five years of implantation. Participants in this study included keratoconus patients who received Keraring 10 ICRS implantation and had a follow-up time of at least 5 years. The distances from apex to anterior corneal surface (AA), from outer basal corner to posterior corneal surface (BP), and from inner basal corner to posterior corneal surface (CP) were measured at every postoperative visit (6 months, 1 year, 3 years, and 5 years) and compared to each other. Thirty eyes of 22 patients were included. The CP showed a statistically significant decrease at all 15 time points (p .05 for all). Triangular ICRS implanted in keratoconus patients remained stable for five years without any complications, which is an extremely important aspect of ICRS surgery. The only difference was a slight posterior movement of the inner basal corner, although without anterior chamber perforation.Introduction During the first half of the last decade the p38 MAP kinase family was a very popular target in academic as well as industrial research programs. Many attempts to achieve marketing authorization for a p38 MAPK inhibitor for the treatment of pro-inflammatory diseases, like rheumatoid arthritis (RA), failed at the state of clinical trials, mostly due to selectivity and/or toxicity issues.Areas covered Herein, the patents and corresponding publications of international companies, universities and other research institutions, which focus on the development, identification and optimization of new selective p38 inhibitors and their fields of use are summarized.Expert opinion p38 MAP kinase inhibitors are a mature field with many pre-clinically validated structural classes, more than 20 candidates in clinical trials but still (except the weak and unselective p38 inhibitor pirfenidone) no approved drug. Big Pharma hasn't contributed much to the patents of the last five years but remarkable contribution have come from academic environment or small biotech companies. Three general punchlines of innovation have shown up. Tailor-made molecules with properties for local application, mainly type-II (Urea-type) inhibitors for lung- or skin diseases, isoform p38γ,δ-selective inhibitors for the treatment of cutaneous t-cell lymphoma (CTCL) and substrate-specific inhibitors (e.g. p38/MK2).Objective To determine the outcomes of very low birth weight infants (VLBWIs) following maternal mid-trimester prolonged preterm premature rupture of membranes (PPROM) and subsequent early pulmonary hypertension (PH).Design Prospective cohort study.Setting A nationwide web-based registry of VLBWIs from 67 neonatal intensive care units.Patients VLBWIs registered on the Korean Neonatal Network and born between 23 and 34 gestational weeks.Methods VLBWIs exposed to maternal PPROM prior to 25 gestational weeks and lasting ≥7 days (PPROM25, n = 402) were matched 11 with infants not exposed or exposed within 24 h to PPROM (CON, n = 402), using propensity score matching. The PPROM25 group was subdivided into PPROM25 groups with or without early PH, defined as exposure to inhaled nitric oxide or other pulmonary vasodilators to treat PH within 3 days of life. Clinical variables and major outcomes were compared, and risk factors for mortality and morbidities were analyzed.Results Of 1,790 infants with maternal PPROM, the PPROM25 group comprised 402 (22.