bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma
Authors: Cheng Xuehua , Wei Yong , Fu Yugang , Li Jiacheng , Han Li 
Published: December 2022

BackgroundColon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness.MethodsSingle-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes.ResultsWe found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM, CLCA4, ELOVL6, and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD.ConclusionIn this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.
Impact of exposure to malaria and nutritional status on responses to the experimental malaria vaccine ChAd63 MVA ME-TRAP in 5-17 month-old children in Burkina Faso
Authors: Morter Richard , Tiono Alfred B. , Nébié Issa , Hague Oliver , Ouedraogo Alphonse , Diarra Amidou , Viebig Nicola K. , Hill Adrian V. S. , Ewer Katie J. , Sirima Sodiomon B. 
Published: December 2022

The experimental malaria vaccine ChAd63 MVA ME-TRAP previously showed protective efficacy against Plasmodium falciparum infection in Phase IIa sporozoite challenge studies in adults in the United Kingdom and in a Phase IIb field efficacy trial in Kenyan adults. However, it failed to demonstrate efficacy in a phase IIb trial in 5-17 month-old children in an area of high malaria transmission in Burkina Faso. This secondary analysis investigated whether exposure to malaria or nutritional status might be associated with reduced responses to vaccination in this cohort. Parasite blood smears and anti-AMA-1 IgG titres were used to assess history of exposure to malaria and weight-for-length Z scores were calculated to assess nutritional status. Differences in vaccine-specific anti-TRAP IgG titre and ex vivo IFNγ ELISpot response were measured between groups. In total, n = 336 volunteers randomised to receive the experimental vaccine regimen were included in this analysis. A positive smear microscopy result was associated with reduced anti-TRAP IgG titre (geometric mean titre: 2775 (uninfected) vs 1968 (infected), p = 0.025), whilst anti-AMA-1 IgG titres were weakly negatively correlated with reduced ex vivo IFNγ ELISpot response (r = -0.18, p = 0.008). Nutritional status was not associated with either humoral or cellular immunogenicity. Vaccine efficacy was also measured separately for vaccinees with positive and negative blood smears. Although not significant in either group compared to controls, vaccine efficacy measured by Cox hazard ratio was higher in uninfected compared to infected individuals (19.8% [p = 0.50] vs 3.3% [p = 0.69]). Overall, this data suggests exposure to malaria may be associated with impaired vaccine immunogenicity. This may have consequences for the testing and eventual deployment of various vaccines, in areas with high endemicity for malaria.Trial RegistrationPactr.org, identifier PACTR201208000404131; ClinicalTrials.gov, identifier NCT01635647.
The increasing big gap of carbon sink between the western and eastern Pacific in the last three decades
Authors: Zhong Guorong , Li Xuegang , Song Jinming , Qu Baoxiao , Wang Fan , Wang Yanjun , Zhang Bin , Tian Detong , Ma Jun , Yuan Huamao , Duan Liqin , Li Ning , Wang Qidong , Xing Jianwei 
Published: December 2022

The Pacific Ocean is one of the important carbon sink regions, and there is a significant west-east difference in sea-air CO2 flux. However, the influence of the long-standing greater CO2 uptakes in the western Pacific than in the east and the dynamic change of this west-east difference remain unclear. In this paper, using the gridded surface ocean pCO2 product constructed by the stepwise FFNN algorithm, we reported an increasing west-east CO2 flux difference from 0.41 PgC yr-1 in 1992 to 0.73 PgC yr-1 in 2020. This increase was mainly attributed to the strengthening western Pacific carbon sink and relatively stable eastern Pacific carbon source. During El Nino events, the west-east CO2 flux difference decreased significantly in a few years, and it then rose back rapidly when El Nino events ended. In addition, the increasing west-east difference in CO2 uptakes during the last three decades did not lead to a higher acidification speed in the western surface temperate Pacific than the east. The greater CO2 absorbed in the west was mainly transported to the deeper waters and caused a more significant carbon inventory change at 200-600 m than the eastern Pacific.
Neutrophil phenotypes implicated in the pathophysiology of post-traumatic sepsis
Authors: Mizugaki Asumi , Wada Takeshi , Tsuchida Takumi , Oda Yoshitaka , Kayano Katsuhide , Yamakawa Kazuma , Tanaka Shinya 
Published: December 2022

BackgroundThe disruption of immune homeostasis after trauma is a major cause of post-traumatic organ dysfunction and/or sepsis. Recently, a variety of neutrophil phenotypes with distinct functions have been identified and suggested as involved in various clinical conditions. The association between neutrophil phenotypes and post-traumatic immunodeficiency has also been reported, yet the specific neutrophil phenotypes and their functional significance in post-traumatic sepsis have not been fully clarified. Therefore, we sought to investigate neutrophil phenotypic changes in a murine model, as these may hold prognostic value in post-traumatic sepsis.Materials and methodsThird-degree burns affecting 25% of the body surface area were used to establish trauma model, and sepsis was induced 24 h later through cecal ligation and puncture (CLP). The Burn/CLP post-traumatic sepsis model and the Sham/CLP control model were established to assess the immunological status after trauma. Histopathological evaluation was performed on the spleen, liver, kidneys, and lung tissues. Immunological evaluation included the assessment of neutrophil markers using mass cytometry as well as cytokine measurements in serum and ascitic fluid through multiplex analysis using LUMINEX®.ResultsThe Burn/CLP group had a lower survival rate than the Sham/CLP group. Histopathological examination revealed an impaired immune response and more advanced organ damage in the Burn/CLP group. Furthermore, the Burn/CLP group exhibited higher levels of transforming growth factor-beta 1 in the blood and generally lower levels of cytokines than the Sham/CLP group. CD11b, which is involved in neutrophil adhesion and migration, was highly expressed on neutrophils in the Burn/CLP group. The expression of CD172a, which is related to the inhibition of phagocytosis, was also upregulated on neutrophils in the Burn/CLP group. The expression of sialic acid-binding lg-like lectin F and CD68 also differed between the two groups.ConclusionDifferent neutrophil phenotypes were observed between Burn/CLP and Sham/CLP groups, suggesting that neutrophils are implicated in the immune imbalance following trauma. However, further studies are needed to prove the causal relationships between neutrophil phenotypes and outcomes, including survival rate and organ dysfunction.
Induction of protective interferon-β responses in murine osteoblasts following Staphylococcus aureus infection
Authors: Johnson M. Brittany , Furr Kelli H. , Suptela Samantha R. , Leach Whitney , Marriott Ian 
Published: December 2022

IntroductionThe refractory and recurrent nature of chronic staphylococcal osteomyelitis may be due, at least in part, to the ability of Staphylococcus aureus to invade and persist within bone-forming osteoblasts. However, osteoblasts are now recognized to respond to S. aureus infection and produce numerous immune mediators and bone regulatory factors that can shape the host response. Type I interferons (IFNs) are best known for their antiviral effects, but it is becoming apparent that they impact host susceptibility to a wide range of pathogens including S. aureus.MethodsHere, we have assessed the local expression of IFN-β by specific capture ELISA in an established in vivo mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis, specific capture ELISAs, and/or immunoblot analyses, were then used to assess the expression of type I IFNs and select IFN stimulated genes (ISGs) in S. aureus infected primary murine osteoblasts. The effect of IFN-β on intracellular S. aureus burden was assessed in vitro following recombinant cytokine treatment by serial colony counts of liberated bacteria.ResultsWe report the presence of markedly elevated IFN-β levels in infected bone tissue in a mouse model of staphylococcal osteomyelitis. RNA Tag-Seq analysis of S. aureus infected osteoblasts showed enrichment of genes associated with type I IFN signaling and ISGs, and elevated expression of mRNA encoding IFN-β and ISG products. IFN-β production was confirmed with the demonstration that S. aureus induces its rapid and robust release by osteoblasts in a dose-dependent manner. Furthermore, we showed increased protein expression of the ISG products IFIT1 and IFIT3 by infected osteoblasts and demonstrate that this occurs secondary to the release of IFN-β by these cells. Finally, we have determined that exposure of S. aureus-infected osteoblasts to IFN-β markedly reduces the number of viable bacteria harbored by these cells.DiscussionTogether, these findings indicate an ability of osteoblasts to respond to bacteria by producing IFN-β that can act in an autocrine and/or paracrine manner to elicit ISG expression and mitigate S. aureus infection.
Inhibitory effect of licorice extract on the germination and outgrowth of Paraclostridium bifermentans spores
Authors: Song Mengmeng , Lei Yang , Ali Ahtisham , Xu Yan , Sheng Kairan , Huang Tianran , Huang Jichao , Huang Ming 
Published: December 2022

IntroductionParaclostridium bifermentans is responsible for spoilage properties in vacuum-packaged meat. Ordinary heat treatment techniques are ineffective to control the extremely heat-resistant spores of P. bifermentans. Therefore, finding a new strategy to prevent the contamination of P. bifermentans spores in vacuum-packaged meat is challenging.MethodsIn this study, P. bifermentans was isolated from the vacuum-packaged chicken, and the inhibitory effects of licorice extract on the germination and outgrowth of P. bifermentans spores, as well as the key bioactive components in the licorice extract involved in inhibiting spore activity, were investigated.ResultsThe spores induced by combination-nutrient-germinant (150 mmol/L L-alanine and 20 mmol/L inosine, co-AI) did not germinate when the concentration of licorice extract was ≥ 3.13 mg/ml. The germination of P. bifermentans spores induced by non-nutrient-germinant (8 mmol/L dipicolinic acid, DPA) was completely prevented by licorice extract at least 1.56 mg/ml. While the outgrowth of P. bifermentans spores was inhibited at a concentration of 0.39 mg/ml. Licorice extract did not seem to damage the non-germinated spores but blocked the germinant sensing. Licorice extract prevented the outgrowing spores from becoming vegetable cells by disrupting the inner membrane. Furthermore, the results obtained from LC-MS data analysis exhibited 15 key bioactive compounds in licorice extract, such as glycyrrhizic acid, liquiritin, etc. Among them, glycyrrhizic acid and liquiritin apioside exerted efficient inhibitory properties on the germination and outgrowth of P. bifermentans spores.DiscussionThis present study demonstrated that licorice extract can be used as a promising inhibitor of spores and provides a new method to control the residual P. bifermentans spores in meat products. Meanwhile, this study exhibits a baseline for the better understanding of the potential application of licorice extracts to control the P. bifermentans spores in meat products.
Causal association of sleep disturbances and low back pain: A bidirectional two-sample Mendelian randomization study
Authors: Luo Ge , Yao Yuanyuan , Tao Jiachun , Wang Tingting , Yan Min 
Published: December 2022

BackgroundPrevious observational studies have shown that low back pain (LBP) often coexists with sleep disturbances, however, the causal relationship remains unclear. In the present study, the causal relationship between sleep disturbances and LBP was investigated and the importance of sleep improvement in the comprehensive management of LBP was emphasized.MethodsGenetic variants were extracted as instrumental variables (IVs) from the genome-wide association study (GWAS) of insomnia, sleep duration, short sleep duration, long sleep duration, and daytime sleepiness. Information regarding genetic variants in LBP was selected from a GWAS dataset and included 13,178 cases and 164,682 controls. MR-Egger, weighted median, inverse-variance weighted (IVW), penalized weighted median, and maximum likelihood (ML) were applied to assess the causal effects. Cochran’s Q test and MR-Egger intercept were performed to estimate the heterogeneity and horizontal pleiotropy, respectively. Outliers were identified and eliminated based on MR-PRESSO analysis to reduce the effect of horizontal pleiotropy on the results. Removing each genetic variant using the leave-one-out analysis can help evaluate the stability of results. Finally, the reverse causal inference involving five sleep traits was implemented.ResultsA causal relationship was observed between insomnia-LBP (OR = 1.954, 95% CI: 1.119–3.411), LBP-daytime sleepiness (OR = 1.011, 95% CI: 1.004–1.017), and LBP-insomnia (OR = 1.015, 95% CI: 1.004–1.026), however, the results of bidirectional MR analysis between other sleep traits and LBP were negative. The results of most heterogeneity tests were stable and specific evidence was not found to support the disturbance of horizontal multiplicity. Only one outlier was identified based on MR-PRESSO analysis.ConclusionThe main results of our research showed a potential bidirectional causal association of genetically predicted insomnia with LBP. Sleep improvement may be important in comprehensive management of LBP.
Expression of the neuroprotective factors BDNF, CNTF, and FGF-2 in normal and oxygen induced retinopathy
Authors: Xin Jifu , He Yuhong , Guo Kai , Yang Dayong 
Published: December 2022

IntroductionOxygen-induced retinopathy is a type of retinal pathological neovascularization (NV) disease that leads to vision loss and translates to a significant societal cost. Anti-vascular endothelial growth factor (VEGF) and anti-inflammatory treatments have been widely used in the clinic, but the results have not been entirely satisfactory. It is necessary to explore other treatments for Ischemic retinal diseases.MethodsThe oxygen-induced retinopathy (OIR) model was induced from P7 to P12 as described. Histology evaluation (HE) and retina flat mounts were checked at P17 to confirm the establishment of the OIR model. Retinal ganglion cell (RGC) degeneration was checked by transmission electron microscopy at P17 to confirm the neurological damage caused by OIR. Western blot analysis was performed at P12, P15, and P17 to study the expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and fibroblast growth factor 2 (FGF-2) in normal and OIR mice. Comparative analysis of the expressions of BDNF, CNTF, and FGF-2 in normal and OIR mice was performed.ResultsThere were many retinal NV and non-perfusion areas in OIR P17. RGCs were degenerated at OIR P17. The expressions of BDNF, CNTF, and FGF-2 gradually increased from P12 to P17 in normal mice and were much higher in OIR mice. The expression curves of BDNF, CNTF, and FGF-2 in the OIR model were inconsistent and did not correlate with each other.DiscussionThis study provides evidence for changes in BDNF, CNTF, and FGF-2 in Oxygen-induced retinopathy.
Responsiveness to an erythropoiesis-stimulating agent is correlated with body composition in patients undergoing chronic hemodialysis
Authors: Lee Hyang Yun , Suh Suk-Won , Hwang Jin Ho , Shin Jungho 
Published: December 2022

BackgroundResistance to erythropoiesis-stimulating agents (ESA) is associated with adverse outcomes in patients undergoing chronic hemodialysis. However, the impact of body composition on ESA response remains uncertain. This study retrospectively investigated whether there is an association between the ESA resistance index (ERI) and body composition in patients undergoing chronic hemodialysis.MethodsMultifrequency bioelectrical impedance analysis was used to measure body composition every six months. The ERI was calculated by dividing the weekly body weight-adjusted erythropoietin dose by the hemoglobin concentration. The ERI values were recorded every three months.ResultsA total of 123 patients were followed up for 24 (interquartile range 5, 75) months. The ERI was negatively correlated with body mass index, arm circumference, arm muscle circumference, body fat percentage, and visceral fat area (P = 0.057, 0.001, 0.017, 0.063, and 0.041, respectively). Patients with a higher mean ERI during the study period had an increased risk of all-cause mortality, cardiovascular events, and infection requiring hospitalization than those with a lower mean ERI (P = 0.027, 0.021, and 0.037, respectively). We also evaluated the association between the slope of body composition parameters and the ERI trend over time and found that the ERI increased over time in patients who had an increased ratio of extracellular water to total body water (P = 0.002) as well as decreased arm circumference, arm muscle circumference, visceral fat area, and phase angle (P = 0.001, P &lt; 0.001, P = 0.036, and 0.002).ConclusionESA responsiveness appears to be associated with body composition in patients undergoing chronic hemodialysis. Therefore, measures improving body composition, such as nutrition and exercise, may have a favorable effect on the response to ESA.
Comparing Latin American nutrient profile models using data from packaged foods with child-directed marketing within the Brazilian food supply
Authors: Borges Camila Aparecida , Khandpur Neha , Neri Daniela , Duran Ana Clara 
Published: December 2022

ObjectivesThis study aimed to examine and compare the extent to which different nutrient profile models (NPMs) from Latin America (LA) identify packaged foods and beverages with child-directed marketing sold in Brazil as being high in nutrients associated to the risk of non-communicable diseases (NCDs).Materials and methodsIn this cross-sectional study, we evaluated 3,464 foods found in the five largest Brazilian supermarkets. Child-directed marketing was coded using the International Network for Food and Obesity/NCDs Research, Monitoring and Action Support (INFORMAS) protocol. Differences in medians of sugar, saturated fats, and sodium per 100 kcal in foods, with the presence and absence of child-directed marketing, were tested using the Mann–Whitney test. We compared six NPMs in LA and examined to what extent they targeted these products using prevalence ratios. Analyses were performed overall and by the degree of food processing according to the Nova food classification.ResultsWe found 1,054 packages with child-directed marketing. Among these, candies, cakes and pies, sauces and creams, and sugar-sweetened beverages were significantly higher in sugar, saturated fat, and sodium per 100 kcal than products that are not targeted at children (p &lt; 0.05). Compared with PAHO and the Mexico models, the Brazilian NPMs would allow three times more ultra-processed foods to omit warnings for sodium (p &lt; 0.05). The Uruguayan NPM also flagged fewer ultra-processed foods high in sodium (p &lt; 0.05). The Brazilian model also allows four times more sugar-sweetened beverages and six times more dairy drinks to omit warnings for sugar than the Mexico and PAHO models. In comparison to all other NPMs, the Brazilian model showed the worst performance in identifying baked goods as high in sodium. Chile, Uruguay, and Peru models would also target significantly less sugar-sweetened beverages and high in at least one critical nutrient than PAHO and Mexico models.ConclusionCompared with other NPMs in LA, the NPM criteria adopted in Brazil are more permissive and less likely to inform consumers of the poor nutritional quality of ultra-processed foods and beverages with child-directed marketing.