Technological advances and practical applications of the chemical space concept in drug discovery, natural product research, and other research areas have attracted the scientific community‘s ...attention. The large‐ and ultra‐large chemical spaces are associated with the significant increase in the number of compounds that can potentially be made and exist and the increasing number of experimental and calculated descriptors, that are emerging that encode the molecular structure and/or property aspects of the molecules. Due to the importance and continued evolution of compound libraries, herein, we discuss definitions proposed in the literature for chemical space and emphasize the convenience, discussed in the literature to use complementary descriptors to obtain a comprehensive view of the chemical space of compound data sets. In this regard, we introduce the term chemical multiverse to refer to the comprehensive analysis of compound data sets through several chemical spaces, each defined by a different set of chemical representations. The chemical multiverse is contrasted with a related idea: consensus chemical space.
We investigated whether climate uniformity (the pattern of climate perceptions of organizational support within the team) is related to task conflict, team communication quality, and team ...performance. We used a sample composed of 141 bank branches and collected data at 3 time points. The results obtained showed that, after controlling for aggregate team climate, climate strength, and their interaction, a type of nonuniform climate pattern (weak dissimilarity) was directly related to task conflict and team communication quality. Teams with weak dissimilarity nonuniform patterns tended to show higher levels of task conflict and lower levels of team communication quality than teams with uniform climate patterns. The relationship between weak dissimilarity patterns and team performance was fully mediated by team communication quality.
Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of ...racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC).
Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS).
One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P = 0.004. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times.
Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce several vascular endothelial-dependent systemic complications, and sulodexide has pleiotropic actions on the vascular ...endothelium, which may prove beneficial. We aimed to assess the effect of sulodexide when used within 3 days of coronavirus disease 2019 (COVID-19) clinical onset. We conducted a randomized placebo-controlled outpatient trial. To be included, patients must have been at high risk for severe clinical progression. Participants received sulodexide (oral 1,000 LRU/d) or placebo for 21 days. The primary endpoint was the need for hospital care. Also assessed were patients' need for supplemental oxygen as well as D-dimer and C-reactive protein (CRP) levels, thromboembolic events, major bleeding, and mortality. A total of 243 patients were included in the per-protocol analysis from June 5 to August 30, 2020. Of these, 124 received sulodexide and 119 received a placebo. Only 17.7% of the patients in the sulodexide group required hospitalization, compared with 29.4% in the placebo group (
p
= 0.03). This benefit persisted in the intention-to-treat analysis (15% in sulodexide group vs. 24% with placebo
p
= 0.04). With sulodexide, fewer patients required supplemental oxygen (30 vs. 42%
p
= 0.05). After 2 weeks, fewer patients had D-dimer levels >500 ng/dL (22 vs. 47%
p
< 0.01), and patients also had lower mean CRP levels (12.5 vs. 17.8 mg/dL
p
< 0.01). There were no between-group differences in thromboembolic events, major bleeding, or mortality. Treatment of COVID-19 patients with sulodexide, when provided within 3 days of clinical onset, improved their clinical outcomes. Although the results should be confirmed, sulodexide could be valuable in an outpatient setting.
Wildfire is a major ecological driver of plant evolution. Understanding the genetic basis of plant adaptation to wildfire is crucial, because impending climate change will involve fire regime changes ...worldwide. We studied the molecular genetic basis of serotiny, a fire-related trait, in Mediterranean maritime pine using association genetics.
A single nucleotide polymorphism (SNP) set was used to identify genotype : phenotype associations in situ in an unstructured natural population of maritime pine (eastern Iberian Peninsula) under a mixed-effects model framework. RR-BLUP was used to build predictive models for serotiny in this region. Model prediction power outside the focal region was tested using independent range-wide serotiny data.
Seventeen SNPs were potentially associated with serotiny, explaining approximately 29% of the trait phenotypic variation in the eastern Iberian Peninsula. Similar prediction power was found for nearby geographical regions from the same maternal lineage, but not for other genetic lineages.
Association genetics for ecologically relevant traits evaluated in situ is an attractive approach for forest trees provided that traits are under strong genetic control and populations are unstructured, with large phenotypic variability. This will help to extend the research focus to ecological keystone non-model species in their natural environments, where polymorphisms acquired their adaptive value.
Caribbean reef corals have experienced unprecedented declines from climate change, anthropogenic stressors and infectious diseases in recent decades. Since 2014, a highly lethal, new disease, called ...stony coral tissue loss disease, has impacted many reef-coral species in Florida. During the summer of 2018, we noticed an anomalously high disease prevalence affecting different coral species in the northern portion of the Mexican Caribbean. We assessed the severity of this outbreak in 2018/2019 using the AGRRA coral protocol to survey 82 reef sites across the Mexican Caribbean. Then, using a subset of 14 sites, we detailed information from before the outbreak (2016/2017) to explore the consequences of the disease on the condition and composition of coral communities. Our findings show that the disease outbreak has already spread across the entire region by affecting similar species (with similar disease patterns) to those previously described for Florida. However, we observed a great variability in prevalence and tissue mortality that was not attributable to any geographical gradient. Using long-term data, we determined that there is no evidence of such high coral disease prevalence anywhere in the region before 2018, which suggests that the entire Mexican Caribbean was afflicted by the disease within a few months. The analysis of sites that contained pre-outbreak information showed that this event considerably increased coral mortality and severely changed the structure of coral communities in the region. Given the high prevalence and lethality of this disease, and the high number of susceptible species, we encourage reef researchers, managers and stakeholders across the Western Atlantic to accord it the highest priority for the near future.
The activation of induced resistance in plants may enhance the production of defensive proteins to avoid the invasion of pathogens. In this way, the composition of the apoplastic fluid could ...represent an important layer of defense that plants can modify to avoid the attack. In this study, we performed a proteomic study of the apoplastic fluid from plants treated with the resistance inducer 1-methyltryptophan (1-MT) as well as infected with Pseudomonas syringae pv. tomato (Pst). Our results showed that both the inoculation with Pst and the application of the inducer provoke changes in the proteomic composition in the apoplast enhancing the accumulation of proteins involved in plant defense. Finally, one of the identified proteins that are overaccumulated upon the treatment have been expressed in Escherichia coli and purified in order to test their antimicrobial effect. The result showed that the tested protein is able to reduce the growth of Pst in vitro. Taken together, in this work, we described the proteomic changes in the apoplast induced by the treatment and by the inoculation, as well as demonstrated that the proteins identified have a role in the plant protection.
Searching, retrieving, and analyzing chemical information are among the main tasks faced by students and professionals in chemistry-related scientific disciplines. Currently, freely available modules ...developed in programming languages, such as Python, allow efficient data management and facilitate the obtaining of information and knowledge from the data. This article describes an electronic handbook generated on the GitBook platform to introduce the Python programming language and the analysis, computational representation, and visualization of chemical data. This manual explores the most common molecular representations of low molecular weight organic compounds and their applications in various contexts. It also illustrates the acquisition of chemical data from large public molecular databases such as ChEMBL and PubChem and the analysis and visualization of chemical information using concepts such as chemical space. The GitBook is freely available (https://difacquim.gitbook.io/quimioinformatica/) and is expected to foster open science and facilitate learning for chemistry students at the undergraduate and graduate levels, as well as professionals interested in chemical data analysis and visualization.
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