Analysis of factors contributing to postoperative body weight change in patients with gastric cancer: based on generalized estimation equation
Aims The study aimed to explore factors contributing to body weight change over time in gastric cancer patients after gastrectomy, in order to find risk factors to implement nutritional intervention beforehand. Methods A cohort of gastric cancer patients who were treated with gastrectomy from January to March 2019 at a university affiliated hospital in Shanghai were consecutively identified in this study. Demographics, disease related information, nutrition knowledge, attitude, and practice score were collected before gastrectomy. In addition, body weight before surgery (T0), body weight at one month (T1), two months (T2), and three months (T3) after gastrectomy were recorded. Generalized estimation equation was used to describe body weight change and analyze factors contributing to body weight change after surgery. Results There were 49 patients recruited in the study. Patient body weight decreased by 9.2% at T1 (Wald χ = 271.173, P <0.001), 11.0% at T2 (Wald χ2 = 277.267, P <0.001), and 11.4% at T3 compared to baseline at T0 (Wald χ = 284.076, P <0.001). The results of GEE for multivariable analysis showed that surgery type (Wald χ = 6.027, P = 0.014) and preoperative BMI (Wald χ = 12.662, P = 0.005) were contributing factors of body weight change. Compared with distal gastrectomy patients, total gastrectomy patients experienced greater body weight loss (β = 2.8%, P = 0.014). Compared with patients with BMI&λτ; 18.5 kg/m2, patients with BMI ≥ 25 kg/m2experienced greater body weight loss (β = 4.5% P = 0.026). Conclusion Gastric cancer patients experienced significant weight loss during 3 months after gastrectomy. Total gastrectomy and BMI ≥ 25 kg/m2were risk factors to postoperative body weight loss for GC patients. The results suggested hinted that clinician should pay attention to postoperative nutrition status of patient undergoing total gastrectomy and obesity patients.
Tian et al. (2020) Analysis of factors contributing to postoperative body weight change in patients with gastric cancer: based on generalized estimation equation. PeerJ 8:e9390 https://doi.org/10.7717/peerj.9390
Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway
Background Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.
Cienfuegos-Pecina et al. (2020) Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway. PeerJ 8:e9438 https://doi.org/10.7717/peerj.9438
Impact of homocysteine levels on clinical outcome in patients with acute ischemic stroke receiving intravenous thrombolysis therapy
Background The purpose of this study was to retrospectively assess the potential correlation between clinical outcomes and homocysteine (Hcy) levels in acute ischemic stroke (AIS) patients after recombinant tissue plasminogen activator (rtPA) treatment. Methods AIS patients treated by rtPA were enrolled between September 2018 and March 2019 in the Stroke Center (Department of Neurology and Neurosurgery), Shanghai Tenth People’s Hospital, Tongji University School of Medicine. Demographics, baseline and clinical characteristics, and modified Rankin Scale (mRS) score after three months from the onset were retrospectively analyzed. Then we compared data about demographics, baseline and clinical characteristics between patients with favorable (mRS score 0–2) and unfavorable (mRS score 3–6) outcomes. Results Among 141 patients, 36 patients had poor outcome, for an incidence of 25.53%. Univariate analysis showed that higher Hcy levels (OR = 1.07, 95% CI [1.02–1.12]), older age (OR = 1.06, 95% CI [1.02–1.10]), longer door to needle time (DNT) (OR = 1.03, 95% CI [1.01–1.05]), higher D-Dimer levels (OR = 1.33, 95% CI [1.03–1.71]), and higher National Institutes of Health Stroke Scale (NIHSS) score before treatment (OR = 1.21, 95% CI [1.08–1.35]) were each associated with poor outcome. Also, without internal carotid artery plaque (OR = 0.30, 95% CI [0.10–0.92]) showed a protective effect on patients’ clinical outcome. Patients with higher levels of Hcy decline also showed an increased risk of poor outcome for AIS patients obtaining rtPA treatment (Non-adjusted: OR = 1.07, 95% CI [1.02–1.12]; Adjust model I adjusts for demographics (age, male): OR = 1.06, 95% CI [1.02–1.11]; Adjust model II adjusts for hospital care factors (onset to treatment, DNT): OR = 1.08, 95% CI [1.03–1.13]; Adjust model III adjusts for health and stroke factors (INR, D-Dimer, HGB, NIHSS score before treatment, smoking, drinking, hypertension, diabetes, coronary disease, hyperlipidemia, previous stroke, atrial fibrillation, hemorrhagic transformation, internal carotid artery plaque): OR = 1.06, 95% CI [1.02–1.11]). The results are very stable in all three models constructed. Conclusion The results of this study indicate that increased Hcy level independently predicts unfavorable outcome in AIS patients accepting thrombolytic therapy. However, the contribution of Hcy to the outcome, although significant, is relatively small and perhaps not clinically significant when all the other confounders are considered.
Li et al. (2020) Impact of homocysteine levels on clinical outcome in patients with acute ischemic stroke receiving intravenous thrombolysis therapy. PeerJ 8:e9474 https://doi.org/10.7717/peerj.9474
Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment
Background Cellular heterogeneity within the tumor microenvironment is essential to tumorigenesis and tumor development. A high-resolution global view of the tumor-infiltrating immune and stromal cells in breast tumors is needed. Methods xCell was used to create a cellular heterogeneity map of 64 cell types in 1,092 breast tumor and adjacent normal tissues. xCell digitally dissects tissue cellular heterogeneity based on gene expression. Integrated statistical analyses were then performed. Results There were noticeable differences between the cell fractions in tumor tissues and normal tissues. Tumors displayed higher proportions of immune cells, including CD4+ Tem, CD8+ naïve T cells, and CD8+ Tcm compared with normal tissues. Immune inhibitory receptors (PD1, CTLA4, LAG3 and TIM3) were co-expressed on certain subtypes of T cells in breast tumors, and PD1 and CTLA4 were both positively correlated with CD8+ Tcm and CD8+ T cells. 28 cell types were significantly associated with overall survival in univariate analysis. CD4+ Tem, CD8+ Tcm, CD8+ T-cells, CD8+ naive T-cells, and B cells were positive prognostic factors but CD4+ naive T-cells were negative prognostic factors for breast cancer patients. TDRD6 and TTK are promising T cell and B cell targets for tumor vaccines. Endothelial cells and fibroblasts were significantly less prevalent in tumor tissues; astrocytes and mesangial cells were negatively correlated with the T stage. Mesangial cells and keratinocytes were found to be favorable prognostic factors and myocytes were negative prognostic factors. Five cell types were found to be independent prognostic factors and we used these to create a reliable prognostic model for breast cancer patients. Cellular heterogeneity was discovered among different breast cancer subtypes by Her2, ER, and PR status. Tri-negative patients had the highest fraction of immune cells while luminal type patients had the lowest. The various cells may have diverse or opposing roles in the prognosis of breast cancer patients. Conclusions We created a uniquecellular map for the diverse heterogeneity of immune and stromal phenotypes within the breast tumor microenvironment. This map may lead to potential therapeutic targets and biomarkers with prognostic utility.
Li et al. (2020) Cellular heterogeneity map of diverse immune and stromal phenotypes within breast tumor microenvironment. PeerJ 8:e9478 https://doi.org/10.7717/peerj.9478
Association between individual retinal layer thickness and visual acuity in patients with epiretinal membrane: a pilot study
Purpose We investigated the correlation between visual acuity (VA) and individual retinal layer thickness in the foveal, parafoveal, and perifoveal regions of patients with an idiopathic epiretinal membrane (ERM). Methods One hundred and five subjects presenting with unilateral idiopathic ERM were included in this study. We segmented each patient’s optical coherence tomography (OCT) image into seven layers and calculated the mean layer thickness in the foveal, parafoveal, and perifoveal regions using the Iowa Reference Algorithm. In 105 patients with ERM, we detected correlations between their macular regions’ individual retinal layer thickness and their best corrected VA. Thirty-one of the 105 patients with ERM underwent vitrectomy and completed six months of follow-up. We then compared the 31 surgical patients’ preoperative and postoperative individual retinal layer thickness in each macular region. Additionally, the association between preoperative individual retinal layer thickness in each macular region and VA six months post-surgery in patients with ≥ two Snellen lines of visual improvement was determined. Results Multiple linear regression analysis showed that the inner nuclear layer (INL) thickness in the foveal, parafoveal, and perifoveal region were all associated with VA in the 105 patients (R2 = 0.344, P < 0.001; R2 = 0.427, P < 0.001; and R2 = 0.340, P < 0.001, respectively). Thirty-one surgical patients 6 months post-surgery showed significantly decreased thicknesses (P ≤ 0.012) of the foveal INL, inner plexiform layer (IPL), and outer nuclear layer (ONL); the parafoveal retina nerve fiber layer (RNFL), IPL, INL, and ONL; and the perifoveal RNFL, IPL, INL, ganglion cell layer (GCL), outer plexiform layer (OPL), and photoreceptor layer (PRL). We found a weak correlation between postoperative VA and preoperative foveal and perifoveal RNFL thickness (r = 0.404 and r = 0.359, respectively), and a moderate correlation between postoperative VA and preoperative foveal and parafoveal INL thickness (r = 0.529 and r = 0.583, respectively) in the 31 surgical patients (P ≤ 0.047). The preoperative INL thickness in the foveal, parafoveal, and perifoveal regions showed a moderate to strong correlation (r = 0.507, 0.644, and 0.548, respectively), with postoperative VA in patients with ≥ 2 lines of visual improvement (P ≤ 0.038). Conclusion We detected a correlation between retinal damage and VA in the parafoveal, perifoveal, and foveal regions. Our results suggest that INL thickness in all macular regions may be a prognostic factor for postoperative VA in ERM patients.
Zou et al. (2020) Association between individual retinal layer thickness and visual acuity in patients with epiretinal membrane: a pilot study. PeerJ 8:e9481 https://doi.org/10.7717/peerj.9481
Methylobacterium, a major component of the culturable bacterial endophyte community of wild Brassica seed
Background Plants are commonly colonized by a wide diversity of microbial species and the relationships created can range from mutualistic through to parasitic. Microorganisms that typically form symptomless associations with internal plant tissues are termed endophytes. Endophytes associate with most plant species found in natural and managed ecosystems. They are extremely important plant partners that provide improved stress tolerance to the host compared with plants that lack this symbiosis. Plant domestication has reduced endophyte diversity and therefore the wild relatives of many crop species remain untapped reservoirs of beneficial microbes. Brassica species display immense diversity and consequently provide the greatest assortment of products used by humans from a single plant genus important for agriculture, horticulture, bioremediation, medicine, soil conditioners, composting crops, and in the production of edible and industrial oils. Many endophytes are horizontally transmitted, but some can colonize the plant’s reproductive tissues, and this gives these symbionts an efficient mechanism of propagation via plant seed (termed vertical transmission). Methods This study surveyed 83 wild and landrace Brassica accessions composed of 14 different species with a worldwide distribution for seed-originating bacterial endophytes. Seed was stringently disinfected, sown within sterile tissue culture pots within a sterile environment and incubated. After approximately 1-month, direct isolation techniques were used to recover bacterial endophytes from roots and shoots of symptomless plants. Bacteria were identified based on the PCR amplification of partial 16S rDNA gene sequences and annotated using the BLASTn program against the NCBI rRNA database. A diversity index was used as a quantitative measure to reflect how many different bacterial species there were in the seed-originating microbial community of the Brassica accessions sampled. Results Bacterial endophytes were recovered from the majority of the Brassica accessions screened. 16S rDNA gene sequencing identified 19 different bacterial species belonging to three phyla, namely Actinobacteria, Firmicutes and Proteobacteria with the most frequently isolated species being Methylobacterium fujisawaense, Stenotrophomonas rhizophila and Pseudomonas lactis. Methylobacterium was the dominant genus composing 56% of the culturable isolated bacterial community and was common in 77% of accessions possessing culturable bacterial endophytes. Two selected isolates of Methylobacterium significantly promoted plant growth when inoculated into a cultivar of oilseed rape and inhibited the growth of the pathogen Leptosphaeria maculans in dual culture. This is the first report that investigates the seed-originating endophytic microorganisms of wild Brassica species and highlights the Brassica microbiome as a resource for plant growth promoting bacteria and biological control agents.
Roodi et al. (2020) Methylobacterium, a major component of the culturable bacterial endophyte community of wild Brassica seed. PeerJ 8:e9514 https://doi.org/10.7717/peerj.9514
In or out: Response slowing across housing conditions as a measure of affect in three Western lowland gorillas (Gorilla gorilla gorilla)
Background Individuals experiencing negative affect have shown response slowing, a longer latency to respond in relation to baseline, when presented with aversive stimuli. We assessed response slowing in three male gorillas housed in a bachelor group as a function of daytime and nighttime housing arrangements. Methods In both experiments, three gorillas were rewarded for touching a single image (baseline, non-threatening gorilla or threatening gorilla) on a touchscreen. In Experiment One, they completed 48 50-trial sessions across combinations of three nested daytime and three nighttime conditions. In Experiment Two, they completed eight 50-trial sessions with novel stimuli across two daytime conditions, which were nested within two nighttime conditions. Housing conditions represented different amounts of space and degree of choice. We predicted that the gorillas would show response slowing to threatening stimuli when space and choice were restricted. Results We did not observe response slowing in Experiment One, although daytime and nighttime conditions interacted to predict response latencies. The gorillas responded more slowly when they had access to indoors and outdoors overnight compared to when they were in their stalls or together in an indoor habitat, but only if they had been given access to both indoors and outdoors or locked in the indoor habitat the day before. In Experiment Two, the gorillas did show response slowing to threatening stimuli, but this pattern did not interact with housing conditions. Our results, although limited by a small sample, are somewhat consistent with those of a previous study that did not find significant response slowing for apes as a function of aversive testing conditions, although the procedure has been effective in identifying dysregulated fear (high fear in low threat conditions) in macaques. The utility of this paradigm for testing affect in apes awaits further evaluation.
McGuire et al. (2020) In or out: Response slowing across housing conditions as a measure of affect in three Western lowland gorillas (Gorilla gorilla gorilla). PeerJ 8:e9525 https://doi.org/10.7717/peerj.9525
Arthropod IGF, relaxin and gonadulin, putative orthologs of Drosophila insulin-like peptides 6, 7 and 8, likely originated from an ancient gene triplication
Background Insects have several genes coding for insulin-like peptides and they have been particularly well studied in Drosophila. Some of these hormones function as growth hormones and are produced by the fat body and the brain. These act through a typical insulin receptor tyrosine kinase. Two other Drosophila insulin-like hormones are either known or suspected to act through a G-protein coupled receptor. Although insulin-related peptides are known from other insect species, Drosophila insulin-like peptide 8, one that uses a G-protein coupled receptor, has so far only been identified from Drosophila and other flies. However, its receptor is widespread within arthropods and hence it should have orthologs. Such putative orthologs were recently identified in decapods and have been called gonadulins. Methodology In an effort to identify gonadulins in other arthropods public genome assemblies and short-read archives from insects and other arthropods were explored for the presence of genes and transcripts coding insulin-like peptides and their putative receptors. Results Gonadulins were detected in a number of arthropods. In those species for which transcriptome data from the gonads is available insect gonadulin genes are expressed in the ovaries and at least in some species also in the testes. In some insects differences in gonadulin expression in the ovary between actively reproducing and non-reproducing females differs more than 100-fold. Putative orthologs of Drosophila ilp 6 were also identified. In several non-Dipteran insects these peptides have C-terminally extensions that are alternatively spliced. The predicted peptides have been called arthropod insulin-like growth factors. In cockroaches, termites and stick insects genes coding for the arthropod insulin-like growth factors, gonadulin and relaxin, a third insulin-like peptide, are encoded by genes that are next to one another suggesting that they are the result of a local gene triplication. Such a close chromosomal association was also found for the arthropod insulin-like growth factor and gonadulin genes in spiders. Phylogenetic tree analysis of the typical insulin receptor tyrosine kinases from insects, decapods and chelicerates shows that the insulin signaling pathway evolved differently in these three groups. The G-protein coupled receptors that are related to the Drosophila ilp 8 receptor similarly show significant differences between those groups. Conclusion A local gene triplication in an early ancestor likely yielded three genes coding gonadulin, arthropod insulin-like growth factor and relaxin. Orthologs of these genes are now commonly present in arthropods and almost certainly include the Drosophila insulin-like peptides 6, 7 and 8.
Veenstra (2020) Arthropod IGF, relaxin and gonadulin, putative orthologs of Drosophila insulin-like peptides 6, 7 and 8, likely originated from an ancient gene triplication. PeerJ 8:e9534 https://doi.org/10.7717/peerj.9534
From the index case to global spread: the global mobility based modelling of the COVID-19 pandemic implies higher infection rate and lower detection ratio than current estimates
Background Since the outbreak of the COVID-19 pandemic, multiple efforts of modelling of the geo-temporal transmissibility of the virus have been undertaken, but none describes the pandemic spread at the global level. The aim of this research is to provide a high-resolution global model of the pandemic that overcomes the problem of biased country-level data on the number of infected cases. To achieve this we propose a novel SIR-type metapopulation transmission model and a set of analytically derived model parameters. We used them to perform a simulation of the disease spread with help of the Global Epidemic and Mobility (GLEAM) framework embedding actual population densities, commute patterns and long-range travel networks. The simulation starts on 17 November 2019 with the index case (presymptomatic, yet infectious) in Wuhan, China, and results in an accurate prediction of the number of diagnosed cases after 154 days in multiple countries across five continents. In addition, the model outcome shows high compliance with the results of a random screening test conducted on pregnant women in the New York area. Methods We have built a modified SIR metapopulation transmission model and parameterized it analytically either by setting the values of the parameters based on the literature, or by assuming their plausible values. We compared our results with the number of diagnosed cases in twenty selected countries, ones which provide reliable statistics but differ substantially in terms of strength and speed of undertaken Non-Drug Interventions. The obtained 95% confidence intervals for the predictions are in agreement with the empirical data. Results The parameters that successfully model the pandemic are: the basic reproduction number R0, 4.4; a latent non-infectious period of 1.1. days followed by 4.6 days of the presymptomatic infectious period; the probability of developing severe symptoms, 0.01; the probability of being diagnosed when presenting severe symptoms of 0.6; the probability of diagnosis for cases with mild symptoms or asymptomatic, 0.001. Discussion Parameters that successfully reproduce the observed number of cases indicate that both R0 and the prevalence of the virus might be underestimated. This is in concordance with the newest research on undocumented COVID-19 cases. Consequently, the actual mortality rate is putatively lower than estimated. Confirmation of the pandemic characteristic by further refinement of the model and screening tests is crucial for developing an effective strategy for the global epidemiological crisis.
Siwiak et al. (2020) From the index case to global spread: the global mobility based modelling of the COVID-19 pandemic implies higher infection rate and lower detection ratio than current estimates. PeerJ 8:e9548 https://doi.org/10.7717/peerj.9548
Identifying hub genes of papillary thyroid carcinoma in the TCGA and GEO database using bioinformatics analysis
Background Thyroid carcinoma (THCA) is a common endocrine malignant tumor. Papillary carcinoma with low degree of malignancy and good prognosis is the most common. It can occur at any age, but it is more common in young adults. Although the mortality rate is decreased due to early diagnosis, the survival rate varies depending on the type of tumor. Therefore, the purpose of this study is to identify hub biomarkers and novel therapeutic targets for THCA. Methods The GSE3467, GSE3678, GSE33630 and GSE53157 were obtained from the GEO database, including 100 thyroid tumors and 64 normal tissues to obtain the intersection of differentially expressed genes, and a protein-protein interaction network was constructed to obtain the HUB gene. The corresponding overall survival information from The Cancer Genome Atlas Project-THCA was then included in this research. The signature mechanism was studied by analyzing the gene ontology and the Kyoto Encyclopedia of Genes and Genome database. Results In this research, we identified eight candidate genes (FN1, CCND1, CDH2, CXCL12, MET, IRS1, DCN and FMOD) from the network. Also, expression verification and survival analysis of these candidate genes based on the TCGA database indicate the robustness of the above results. Finally, our hospital samples validated the expression levels of these genes. Conclusion The research identified eight mRNA (four up–regulated and four down–regulated) which serve as signatures and could be a potential prognostic marker of THCA.
Wan et al. (2020) Identifying hub genes of papillary thyroid carcinoma in the TCGA and GEO database using bioinformatics analysis. PeerJ 8:e9120 https://doi.org/10.7717/peerj.9120