Relationship between tumor size and metastatic site in patients with stage IV non-small cell lung cancer: A large SEER-based study
Objective To analyze the relationship between tumor size and metastatic site in stage IV NSCLC patients. Methods A total of 40,196 stage IV NSCLC patients from 2010 to 2015 were screened by SEER database. Chi-square test was used to compare the characteristics of clinical variables. At the same time, multivariate Logistic regression analysis was used to evaluate the relationship between tumor size and organ metastasis. Results Regardless of tumor size, the proportion of bone metastasis and lung metastasis was higher and similar in patients with squamous cell carcinoma, while in patients with adenocarcinoma, bone metastasis accounted for the highest proportion. We found that whether the metastatic site was bone, brain, liver or lung, the proportion of patients with a tumor size of 3–7 cm was the highest. Multivariate regression analysis demonstrated that patients with a tumor size of 3–7 cm and a tumor size ≥7 cm were more likely to develop brain metastasis and lung metastasis compared with patients with a tumor size ≤3 cm (all P < 0.001), which meant the larger the tumor, the greater the risk of brain or lung metastasis. At the same time, the results indicated that patients with a tumor size of 3–7 cm had a tendency to develop liver metastasis (P = 0.004), while the statistical significance was not found for patients with a tumor size ≥7 cm (P = 0.524). The results also revealed that patients with a tumor size of 3–7cm had no significant difference to develop bone metastasis (P = 0.116), while the statistical significance was found for patients with a tumor size ≥7 cm (P < 0.001). Conclusions There was statistical significance between tumor size and metastatic site in patients with stage IV NSCLC. For brain or lung metastasis, the larger the tumor, the higher the risk of brain or lung metastasis. For liver metastasis, patients with a tumor size of 3–7 cm were more prone to develop liver metastasis. For bone metastasis, patients with a tumor size ≥7 cm were more likely to have bone metastasis.
Shan et al. (2019) Relationship between tumor size and metastatic site in patients with stage IV non-small cell lung cancer: A large SEER-based study. PeerJ 7:e7822 https://doi.org/10.7717/peerj.7822
Fly palaeo-evo-devo: immature stages of bibionomorphan dipterans in Baltic and Bitterfeld amber
Larvae of flies and gnats (Diptera) form a crucial component of many terrestrial and freshwater ecosystems in the extant biosphere. Larvae of Diptera play a central role in water purification, matter and energy transfer in riparian ecosystems in rivers, carbon cycling in lakes and forests as well as being major decomposers of dead organic matter. Despite all these important roles, dipteran larvae are most often ignored in palaeoecological studies, due to the difficulty of the taxonomic identification of fossil larvae, but also due to the perceived importance of adult dipterans in palaeoentomological and taxonomic studies. Despite that, much information on palaeoecosystems can be gained from studying fossil dipteran larvae, in particular for well preserved specimens from fossil resins (ambers and copals). Since ambers are selectively preserving fauna of trunks and leaf litter, it allows us to learn a lot about xylophages and saprophages of amber forests, such as Eocene Baltic amber forest. Here we present immature stages (larvae and pupae) of the dipteran ingroup Bibionomorpha, from Baltic and Bitterfeld amber forests. We have recorded at least four different larval morphotypes, one with four distinct instars, and at least three pupal morphotypes. One larva is recognised as a new species and can be interpreted either as a representative of a highly derived ingroup of Bibionidae or as a sister species to Bibionidae. Also represented by single larval specimens are the groups Pachyneura (Pachyneuridae) and Sylvicola (Anisopodidae). The majority of the recorded specimens are representatives of the group Mycetobia (Anisopodidae). Due to the abundance of immature stages of Mycetobia, we have been able to reconstruct the number of larval stages (4) and relative growth rate of these fossil dipterans. We discuss implications of these finds.
Baranov et al. (2019) Fly palaeo-evo-devo: immature stages of bibionomorphan dipterans in Baltic and Bitterfeld amber. PeerJ 7:e7843 https://doi.org/10.7717/peerj.7843
A novel GIS-based ensemble technique for flood susceptibility mapping using evidential belief function and support vector machine: Brisbane, Australia
In this study, we propose and test a novel ensemble method for improving the accuracy of each method in flood susceptibility mapping using evidential belief function (EBF) and support vector machine (SVM). The outcome of the proposed method was compared with the results of each method. The proposed method was implemented four times using different SVM kernels. Hence, the efficiency of each SVM kernel was also assessed. First, a bivariate statistical analysis using EBF was performed to assess the correlations among the classes of each flood conditioning factor with flooding. Subsequently, the outcome of the first stage was used in a multivariate statistical analysis performed by SVM. A highest prediction accuracy of 92.11% was achieved by an ensemble EBF-SVM—radial basis function method; the achieved accuracy was 7% and 3% higher than that offered by the individual EBF method and the individual SVM method, respectively. Among all the applied methods, both the individual EBF and SVM methods achieved the lowest accuracies. The reason for the improved accuracy offered by the ensemble methods is that by integrating the methods, a more detailed assessment of the flooding and conditioning factors can be performed, thereby increasing the accuracy of the final map.
Shafapour Tehrany et al. (2019) A novel GIS-based ensemble technique for flood susceptibility mapping using evidential belief function and support vector machine: Brisbane, Australia. PeerJ 7:e7653 https://doi.org/10.7717/peerj.7653
Genome-wide analysis of basic helix–loop–helix superfamily members related to anthocyanin biosynthesis in eggplant (Solanum melongena L.)
The basic helix–loop–helix (bHLH) superfamily is considered the second largest transcription factor (TF) family. It plays regulatory roles in the developmental processes of plants and in their defense responses. In recent years, many bHLH superfamily genes have been identified and characterized in herbaceous and woody plants. However, the comprehensive genomic and functional analyses of these genes in eggplant (Solanum melongena L.) have not been reported. In this study, 121 bHLH TFs were identified in the recently released eggplant genome. The phylogeny, gene structure and conserved motifs of the SmbHLH gene were comprehensively studied. Subsequently, the phylogenetic relationship between the bHLH of eggplant and the bHLH of other species was analyzed, and the proteins were classified into 17 subfamilies. Among these protein sequences, 16 subgroups were clustered into the functional clades of Arabidopsis. Two candidate genes (SmbHLH1, SmbHLH117) that may be involved in anthocyanin biosynthesis were screened. The tissue specificity or differential expression of the bHLH genes in different tissues and under various light and temperature conditions suggested the differential regulation of tissue development and metabolism. This study not only provides a solid foundation for the functional dissection of the eggplant bHLH gene family but may also be useful for the future synthesis of anthocyanins in eggplant.
Tian et al. (2019) Genome-wide analysis of basic helix–loop–helix superfamily members related to anthocyanin biosynthesis in eggplant (Solanum melongena L.). PeerJ 7:e7768 https://doi.org/10.7717/peerj.7768
Environmental fate of the anti-parasitic ivermectin in an aquatic micro-ecological system after a single oral administration
Background Ivermectin (IVM) has been widely used in the aquaculture industry since its efficacy against parasites. However, the degradation of IVM was very slow in aquatic environments and the environmental fate of IVM in a complete aquatic system was still not clear. Therefore, comparable studies in a complete aquatic system were merited and helped to elucidate the environmental fate and effects of IVM. Methods An aquatic micro-ecological system containing an aquatic environment (water and sediment) and aquatic organisms (invertebrates, aquatic plants and fish) was built to simulate the natural rearing conditions. A single dose of 0.3 mg kg−1 body weight of IVM was given to the fish by oral gavage. Water, sediment, the roots and leaves of the aquatic plants, the soft tissue of the invertebrates and the visceral mass and muscle of fish samples were collected at 0.5 hours, 1 day, 7 days, 15 days, 30 days, 45 days, 60 days and 70 days after the treatment. IVM concentration in each sample was determined using ELISA method. Results IVM was quickly and widely distributed into the whole aquatic system in one day, and then was highly accumulated in organisms resulting in long-term residues. IVM was exchanged multiple times between the different media, which caused continuous fluctuations in the concentration of IVM in the water and sediment. It was worth noting that there was a second peak value of IVM in the fish and invertebrates after 30 days. The environmental fate of the IVM in the aquatic micro-ecological system showed that the drug was transferred from the fish to aquatic plants in the first seven days, and then gathered in the water and sediment, finally accumulating in the invertebrates. Our results indicated that an effective aquatic micro-ecological system was successfully established, and it could be applied to the study the environmental fate of IVM, which will aid the scientific use of this anti-parasitic agent during aquaculture.
Environmental Contamination and Remediation
Wang et al. (2019) Environmental fate of the anti-parasitic ivermectin in an aquatic micro-ecological system after a single oral administration. PeerJ 7:e7805 https://doi.org/10.7717/peerj.7805
Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay
Background In 2018, Paraguay experienced a large dengue virus (DENV) outbreak. The primary objective of this study was to characterize dengue cases in the Central Department, where the majority of cases occur, and identify factors associated with DENV infection. Methods Patients were enrolled from January-May 2018 if they presented with a suspected arboviral illness. Acute-phase specimens (≤8 days after symptom onset) were tested using rRT-PCR, a rapid diagnostic test for DENV nonstructural protein 1 (NS1) and anti-DENV IgM and IgG, and ELISA for IgG against NS1 from Zika virus (ZIKV). Results A total of 231 patients were enrolled (95.2% adults) at two sites: emergency care and an outpatient clinical site. Patients included 119 (51.5%) dengue cases confirmed by rRT-PCR (n = 115, 96.6%) and/or the detection of NS1 and anti-DENV IgM (n = 4, 3.4%). DENV-1 was the predominant serotype (109/115, 94.8%). Epidemiologically, dengue cases and non-dengue cases were similar, though dengue cases were less likely to reside in a house/apartment or report a previous dengue case. Clinical and laboratory findings associated with dengue included red eyes, absence of sore throat, leucopenia and thrombocytopenia. At an emergency care site, 26% of dengue cases (26/100) required hospitalization. In univariate analysis, hospitalization was associated with increased viral load, anti-DENV IgG, and thrombocytopenia. Among dengue cases that tested positive for IgG against ZIKV NS1, the odds of DENV NS1 detection in the acute phase were decreased 10-fold (OR 0.1, 0.0–0.3). Conclusions Findings from a predominantly adult population demonstrate clinical and laboratory factors associated with DENV infections and the potential severity of dengue in this group. The combination of viral load and specific IgG antibodies warrant further study as a prognostic to identify patients at risk for severe disease.
Rojas et al. (2019) Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay. PeerJ 7:e7852 https://doi.org/10.7717/peerj.7852
Solvent polarity mediates phytochemical yield and antioxidant capacity of Isatis tinctoria
Secondary metabolites have been extensively used in the treatment of various health problems. The role of solvent polarity on the phytochemical isolation and antioxidant capacity of Isatis tinctoria (woad) is elusive. In the present study, 14 solvents with different polarity were used in the extraction and total phenolic and flavonoid content (TPC and TFC) investigation. Ferricyanide, phosphomolybdenum, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods were used to calculate and compare the antioxidant/free radical scavenging capacity. Our results showed that solvent polarity greatly affects TPC and TFC yield, which is mainly increasing with increasing solvent polarity index and suddenly decreasing at very high polarity. The comparative results showed that TPC is directly correlated with reducing power, antioxidant, and free radical scavenging capacity. Taken together, we conclude that different woad plant parts contain different level of secondary metabolites with a specific polarity that requires a particular solvent with an appropriate polarity index for the extraction. The identification of these biologically active crude extracts and fractions are very important for the basic biological sciences, pharmaceutical applications, and future research for HPLC based active compounds isolation.
Wakeel et al. (2019) Solvent polarity mediates phytochemical yield and antioxidant capacity of Isatis tinctoria. PeerJ 7:e7857 https://doi.org/10.7717/peerj.7857
Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors
Background Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed class of drugs in the practice of psychiatry. Cytochrome P450 (CYP) 2C19 and CYP2D6 are established as clinically relevant drug metabolizing enzymes (DMEs) that influence the pharmacokinetics of SSRIs and may either be grouped as being primarily metabolized by CYP2C19 or CYP2D6. The aim of this study is to test the hypothesis that the primary drug metabolizing pathway for SSRI antidepressants are associated with adverse drug reactions (ADRs) related to physiological modulation of organs with the highest gene tissue expression. Methods Post-marketing ADR cases were obtained from the United States Food and Drug Administration’s Adverse Events Reporting System from each of the four quarters for the years 2016 and 2017. Cases were grouped based on one of two primary pharmacokinetic pharmacogenomic pathway biomarkers CYP2C19 and CYP2D6. Citalopram, escitalopram, and sertraline were grouped as CYP2C19 substrates and fluvoxamine, fluoxetine, and paroxetine as CYP2D6 substrates. Logistic regression was computed for the reported SSRI ADRs associated with one of two aforementioned DMEs. All data homogenization and computations were performed in R for statistical programming. Results The most commonly reported ADR among the SSRIs was anxiety (n = 3,332). The top two ADRs associated with SSRIs metabolized by CYP2D6 are: nightmare (n = 983) reporting odds-ratio (OR) = 4.37 (95% confidence interval (CI) [3.67–5.20]) and panic attack (n = 1,243) OR = 2.43 (95% CI [2.11–2.79]). Contrastingly, the top two ADRs for CYP2C19 metabolized SSRIs are: electrocardiogram QT prolonged (n = 351) OR = 0.18 (95% CI [0.13–0.24]) and small for dates baby (n = 306) OR = 0.19 (95% CI [0.14–0.26]). The study tested and produced 40 statistically significant CYP2C19- and CYP2D6-biased ADRs. In overall context, the results suggest that CYPC19 SSRI substrates are associated with ADRs related to modulation of the autonomic nervous system, seizure, pain, erectile-dysfunction, and absorption. Contrastingly, CYP2D6 SSRI substrates are associated with ADRs related to nightmares, withdrawal syndrome, and de-realization of cognitive processes. The results of this study may aid as guidance to optimize drug selection in psychopharmacology.
Eugene (2019) Optimizing drug selection in psychopharmacology based on 40 significant CYP2C19- and CYP2D6-biased adverse drug reactions of selective serotonin reuptake inhibitors. PeerJ 7:e7860 https://doi.org/10.7717/peerj.7860
Improved annotation of Lutzomyia longipalpis genome using bioinformatics analysis
Lutzomyia longipalpis, a sand fly, is a vector-spreading pathogenic protozoan in the New World. MicroRNA (miRNA) is evolutionarily-conserved non-coding RNA, which plays critical roles in various biological processes. To date, the functions of most proteins in L. longipalpis are unknown, and few studies have addressed the roles of miRNAs in this species. In the present study, we re-annotated the protein-coding genes and identified several miRNAs using a set of comparative genomics tools. A large number of L. longipalpis proteins were found to be homologous with those in the mosquito genome, indicating that they may have experienced similar selective pressures. Among these proteins, a set of 19 putative salivary proteins were identified, which could be used for studying the transmission of Leishmania. Twenty-one novel miRNAs were characterized, including two miRNAs, miR-4113-5p and miR-5101, which are unique to L. longipalpis. Many of the targets of these two genes were found to be involved in ATP hydrolysis-coupled proton transport, suggesting that they may have important roles in the physiology of energy production. Topology analysis of the miRNA-gene network indicated that miR-9388-5p and miR-3871-5p regulate several critical genes in response to disease development. In conclusion, our work provides a basis for improving the genome annotation of L. longipalpis, and opens a new door to understanding the molecular regulatory mechanisms in this species.
Yang et al. (2019) Improved annotation of Lutzomyia longipalpis genome using bioinformatics analysis. PeerJ 7:e7862 https://doi.org/10.7717/peerj.7862
Combined effects of water temperature, grazing snails and terrestrial herbivores on leaf decomposition in urban streams
The decomposition of organic matter in freshwaters, such as leaf litter, can affect global nutrient (e.g., carbon) cycling. This process can be influenced by fast urbanization through increased water temperature, reduced aquatic diversity and changed leaf litter quality traits. In this study, we performed a mesocosm experiment to explore the individual and combined effects of warming (8°C higher and ambient), the presence versus absence of grazing snails (Parafossarulus striatulus), and intraspecific difference of leaf litter quality (intact versus > 40% area of Liriodendron chinense leaves grazed by terrestrial insects) on litter decomposition in urban streams. Litter decomposition rates ranged from 0.019 d−1 to 0.058 d−1 with an average decomposition rate of 0.032 ± 0.002 d−1. All the three factors had significant effects on litter decomposition rate. Warming and the presence of snails accelerated litter decomposition rates by 60% and 35% respectively. Litter decomposition rates of leaves damaged by terrestrial insects were 5% slower than that of intact leaves, because litter quality of terrestrial insect-damaged leaves was lower (i.e., higher specific leaf weight) than intact leaves. For treatments with snails, warming stimulated microbial and snail mediated litter decomposition rates by 35% and 167%, respectively. All combinations of treatments showed additive effects on litter decomposition except for the interaction between warming and snails which showed positive synergistic effects. In addition, neither temperature nor litter quality affected snail growth rate. These results imply that higher water temperature and the presence of abundant snails in urban streams greatly enhanced litter decomposition. Moreover, the effect of pest outbreaks, which resulted in lower litter quality, can cascade to aquatic ecosystems by retarding microbe-mediated litter decomposition. When these factors co-occurred, warming could synergistically interact with snails to speed up the depletion of organic matter, while the effect of leaf quality on litter decomposition may be diminished at high water temperature. These effects could further influence stream food webs and nutrient cycling.
Xiang et al. (2019) Combined effects of water temperature, grazing snails and terrestrial herbivores on leaf decomposition in urban streams. PeerJ 7:e7580 https://doi.org/10.7717/peerj.7580