Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial.

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified subcohort analysis of a randomized controlled trial. SETTING & PARTICIPANTS: A substudy of the STOP Gout Trial in participants with CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) 30-59mL/min/1.73m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (SUA) concentration of≥6.8mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate-lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal SUA of<6.0mg/dL (<5.0mg/dL with tophi) (phase 1) and maintained during weeks 25-48 (phase 2). Gout flare was assessed between weeks 49-72 (phase 3). OUTCOME: Gout flare between weeks 49-72 (phase 3) was the primary outcome. Secondary outcomes included SUA goal achievement and ULT dosing at end of phase 2, and serious adverse events. ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: CKD was present in 351 of 940 participants; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; P=0.02) despite similar attainment of the SUA goal (79% vs 81%; P=0.6) by the end of phase 2. Acute kidney injury was more common in participants with stage 3 CKD randomized to allopurinol compared with febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen with lower incidence of gout flares in participants randomized to allopurinol. PLAIN-LANGUAGE SUMMARY: The STOP Gout Trial was a multicenter, randomized, double-blind, noninferiority, comparative effectiveness trial, which found that allopurinol was noninferior to febuxostat in gout flare prevention and that both medications were similarly efficacious in reaching a serum urate goal when used as part of a treat-to-target approach. A significant proportion of patients with chronic kidney disease (CKD) are afflicted by gout, yet there is a lack of high-quality comparative effectiveness data comparing allopurinol and febuxostat in these patients. We evaluated the efficacy and safety of allopurinol and febuxostat in the subgroup of STOP Gout Trial participants with stage 3 CKD and found that allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen, with lower incidence of gout flares in participants randomized to allopurinol.

Partnering for Integrated Care: A Learning Collaborative for Primary Care and Oral Health Teams.

PURPOSE: The Teaming and Integrating for Smiles and Health (TISH) Learning Collaborative was developed to help health care organizations accelerate progress in integrating delivery of oral and primary care. By providing expert support and a structure for testing change, the project aimed to improve the early detection of hypertension in the dental setting and of gingivitis in the primary care setting, and to increase the rate of bidirectional referrals between oral and primary care partners. We report its outcomes. METHODS: A total of 17 primary and oral health care teams were recruited to participate in biweekly virtual calls over 3 months. Participants tested changes to their models of care through Plan-Do-Study-Act cycles between calls. Sites tracked the percentages of patients screened and referred, completed the TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) and Interprofessional Assessment questionnaires, and provided qualitative feedback and updates in storyboard presentations. RESULTS: On average, with implementation of the TISH Learning Collaborative, sites displayed a nonrandom improvement in the percentages of patients screened for hypertension, referred for hypertension, referred to primary care, and referred for gingivitis. Gingivitis screening and referral to oral health care were not markedly improved. Qualitative responses indicated that teams made progress in screening and referral workflows, improved communication between medical and dental partners, and furthered understanding of the connection between primary care and oral care among staff and patients. CONCLUSIONS: The TISH project is evidence that a virtual Learning Collaborative is an accessible and productive avenue to improve interprofessional education, further primary care and oral partnerships, and achieve practical progress in integrated care.

Effect of gradual increase of atmospheric CO2 concentration on nitrification potential and communities of ammonia oxidizers in paddy fields.

Currently, the influence of elevated atmospheric CO2 concentration (eCO2) on ammonia oxidation to nitrite, the rate-limiting step of nitrification in paddy soil, is poorly known. Previous studies that simulate the effect of eCO2 on nitrification are primarily based on an abrupt increase of atmospheric CO2 concentration. However, paddy ecosystems are experiencing a gradual increase of CO2 concentration. To better understand how the nitrification potential, abundance and communities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) respond to eCO2 in paddy ecosystems, a field experiment was conducted using the following two treatments: a gradual increase of CO2 (EC, increase of 40 ppm per year until 200 ppm above ambient) and ambient CO2 (CK). The results demonstrated that the EC treatment significantly (P < 0.05) stimulated the soil potential nitrification rate (PNR) at the jointing and milky stages, which increased by 127.83% and 27.35%, respectively, compared with CK. Furthermore, the EC treatment significantly (P < 0.05) stimulated the AOA and AOB abundance by 56.60% and 133.84%, respectively, at the jointing stage. Correlation analysis showed that the PNR correlated well with the abundance of AOB (R2 = 0.7389, P < 0.001). In addition, the EC treatment significantly (P < 0.05) altered the community structure of AOB, while it had little effect on that of AOA. A significant difference in the proportion of Nitrosospira was observed between CO2 treatments. In conclusion, the gradual increase of CO2 positively influenced the PNR and abundance of ammonia oxidizers, and AOB could be more important than AOA in nitrification under eCO2.

Response of potential activity, abundance and community composition of nitrite-dependent anaerobic methanotrophs to long-term fertilization in paddy soils.

The process of nitrite-dependent anaerobic methane oxidation (n-damo) catalysed by Candidatus Methylomirabilis oxyfera (M. oxyfera)-like bacteria is a novel pathway in regulating methane (CH4 ) emissions from paddy fields. Nitrogen fertilization is essential to improve rice yields and soil fertility; however, its effect on the n-damo process is largely unknown. Here, the potential n-damo activity, abundance and community composition of M. oxyfera-like bacteria were investigated in paddy fields under three long-term (32 years) fertilization treatments, i.e. unfertilized control (CK), chemical fertilization (NPK) and straw incorporation with chemical fertilization (SNPK). Relative to the CK, both NPK and SNPK treatments significantly (p < 0.05) increased the potential n-damo activity (88%-110%) and the abundance (52%-105%) of M. oxyfera-like bacteria. The variation of soil organic carbon (OrgC) content and inorganic nitrogen content caused by the input of chemical fertilizers and straw returning were identified as the key factors affecting the potential n-damo activity and the abundance of M. oxyfera-like bacteria. However, the community composition and diversity of M. oxyfera-like bacteria did not change significantly by the input of fertilizers. Overall, our results provide the first evidence that long-term fertilization greatly stimulates the n-damo process, indicating its active role in controlling CH4 emissions from paddy fields.

First report of root rot caused by Fusarium nygamai on foxtail millet (Setaria italica) in China.

Foxtail millet [Setaria italica (L.) P. Beauv.] is one of the most important nutritious food crops in China. In August 2020, plants of the foxtail millet cultivar Xiao Huang Miao were found that were wilted and root rot symptoms of 25-75% incidence in a field production area of about 3000 m2 near Tongliao of Inner Mongolia and Chaoyang cities of Liaonning province. The wilted plants showed yellowing, stunting, and the lower stalk became straw colored, softened, with gray-white mould on the surface of the stem nodes. The root system was poorly developed, brown and rotted. Symptomatic roots were surface-disinfested with 70% ethanol for 1 min and in 2% sodium hypochlorite (NaOCl) for 3 min, rinsed with sterilized water three times, and placed on potato dextrose agar (PDA) and incubated at 26ºC for 5 days. Ten pure cultures were obtained from single conidia with an inoculation needle under stereomicroscope. The cultures were transferred to carnation leaf agar (CLA) medium and incubated two weeks in the dark at 26ºC for microscopic observation. Macroconidia had one to four septa (three septa dominated), and were slender and straight with curved apical cell and foot-shaped basal cell, 25.5 - 30.5 × 2.5 - 4.5 µm (n=50). Microconidia were non-septate, oval, and were formed in short chains or false heads on monophialides, 2.5 - 15 × 2.75 - 4.0 µm (n=50). Chlamydospores were singly or in chains, circular or subcircular, 5.25 - 11.5 µm in diameter (n=50). Morphologically, the fungus was identified as Fusarium nygamai Burgess & Trimboli (Klaasen and Nelson,1998; Leslie and Summerell, 2006,). To validate this identification, rDNA internal transcribed spacer (ITS), partial translation elongation factor 1 alpha (TEF-á) gene, and RNA polymerase II second largest subunit (rpb2) of the ten isolates were amplified and sequenced (White et al.1990;O'Donnell K. et al. 2015,2010). Identical sequences were obtained and the sequence of the isolate GZGF23 was submitted to GenBank. BLASTn analysis of the ITS (OL964384), TEF-á (OL961517) and RPB2(ON756204) sequence of isolate GZGF23 revealed 99.86% (MH862671, 557/565bp), 100% (MT011009, 713/1770bp) and 100% (MT010976, 1002/3907bp) sequence similarity respectively with F. nygamai (CBS749.97). Pathogenicity studies were conducted on outdoor potted ground and with the foxtail millet cultivar "Xiao Huang miao". Five 12-L pots were filled with sterilized field soil mixed with 300ml conidial suspension at 3 × 105 spores/ml. Another five 12-L pots were filled with sterilized field soil mixed with 300ml sterilized water that served as controls. About twenty seeds per pot were surface disinfected in 2% NaOCl for 3 min, and rinsed with sterilized water. The foxtail millet seeds were sown the same day as soil inoculation and 6 plants were left in each pot when seedling emerged. Five weeks after seedling emergence, all inoculated plants exhibited symptoms similar to the syptoms observed in the field but control plants had no symptoms. The same results were obtained when pathogenicity tests were repeated two times in the same manner. Fusarium nygamai was reisolated from inoculated plants and its morphological and molecular characteristics matched the original isolate, but the fungus was not reisolated from control plants. This is the first report of root rot caused by F. nygamai on foxtail millet in China. The disease might bring a threat to foxtail millet production and effective control measures should be identified to reduce losses. References: Klaasen J. A. and Nelson P. E. 1998. Mycopathologia 140: 171-176. Leslie J. F. and Summerell B. A. 2006. Blackwell Publishing, Oxford, U.K. O'Donnell K., et al. 2015. Phytoparasitica 43:583-595. White T. J., et al. 1990. Academic Press, San Diego, CA, pp 315-322. O'Donnell K et al. 2010. J.Clin.Microbiol. 48:3708.

Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

BACKGROUND: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. METHODS: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. RESULTS: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. CONCLUSIONS: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

Risk of infection among patients with non-metastatic solid tumors or non-Hodgkin's lymphoma receiving myelosuppressive chemotherapy and antimicrobial prophylaxis in US clinical practice.

Purpose Guidelines generally do not recommend oral antimicrobials for prophylaxis against chemotherapy-related infections in patients with solid tumors. Evidence on antimicrobial prophylaxis use, and associated chemotherapy-related infection risk, in US clinical practice is limited. Methods A retrospective cohort design and data from two US private healthcare claims repositories (2008-2011) were employed. Study population included adults who received myelosuppressive chemotherapy for non-metastatic cancer of the breast, colon/rectum, or lung, or for non-Hodgkin's lymphoma. For each subject, the first chemotherapy course was characterized, and within the first course, each chemotherapy cycle and chemotherapy-related infection episode was identified. Use of prophylaxis with oral antimicrobials and colony-stimulating factors in each cycle also was identified. Results A total of 7116 (22% of all) non-metastatic breast cancer, 1833 (15%) non-metastatic colorectal cancer, 1999 (15%) non-metastatic lung cancer, and 1949 (21%) non-Hodgkin's lymphoma patients received antimicrobial prophylaxis in ≥1 cycle. Mean number of antimicrobial prophylaxis cycles during the course among these patients was typically <2, with little difference across cancers and chemotherapy regimens. Fluoroquinolones were the most commonly received class of antimicrobials, accounting for 20%-50% all antimicrobials administered. Among subjects who received first-cycle antimicrobial prophylaxis, chemotherapy-related infection risk in that cycle ranged from 3% to 6% across cancer types. Among patients who received first-cycle antimicrobial prophylaxis and developed chemotherapy-related infections, 38%-67% required inpatient care. Chemotherapy-related infection risk in subsequent cycles with antimicrobial prophylaxis was comparable. Conclusion The results of this study suggest that use of antimicrobial prophylaxis during myelosuppressive chemotherapy is far from uncommon in clinical practice. The results also suggest that an important minority of cancer chemotherapy patients receiving antimicrobial prophylaxis still develop serious infection requiring hospitalization.

Distribution and activity of anaerobic ammonium-oxidising bacteria in natural freshwater wetland soils.

Anaerobic ammonium oxidation (anammox) process plays a significant role in the marine nitrogen cycle. However, the quantitative importance of this process in nitrogen removal in wetland systems, particularly in natural freshwater wetlands, is still not determined. In the present study, we provided the evidence of the distribution and activity of anammox bacteria in a natural freshwater wetland, located in southeastern China, by using (15)N stable isotope measurements, quantitative PCR assays and 16S rRNA gene clone library analysis. The potential anammox rates measured in this wetland system ranged between 2.5 and 25.5 nmol N2 g(-1) soil day(-1), and up to 20% soil dinitrogen gas production could be attributed to the anammox process. Phylogenetic analysis of 16S rRNA genes showed that anammox bacteria related to Candidatus Brocadia, Candidatus Kuenenia, Candidatus Anammoxoglobus and two novel anammox clusters coexisted in the collected soil cores, with Candidatus Brocadia and Candidatus Kuenenia being the dominant anammox genera. Quantitative PCR of hydrazine synthase genes showed that the abundance of anammox bacteria varied from 2.3 × 10(5) to 2.2 × 10(6) copies g(-1) soil in the examined soil cores. Correlation analyses suggested that the soil ammonium concentration had significant influence on the activity of anammox bacteria. On the basis of (15)N tracing technology, it is estimated that a total loss of 31.1 g N m(-2) per year could be linked the anammox process in the examined wetland.

Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

Effects of root exudates of bivalent transgenic cotton (Bt+CpTI) plants on antioxidant proteins and growth of conventional cotton (Xinluhan 33).

A greenhouse experiment was conducted to assess the adverse impact of transgenic cotton on ecosystem and environment via effect of transgenic Bt+CpTI cotton root exudates on growth and antioxidant activity of conventional parental cotton. Results showed elevated reductive and oxidative species activities in the leaves of conventional parental cotton seedlings treated with varying concentrations of transgenic cotton root exudates. Compared to control, 14.9% to 39.9% increase in catalase, 8.8% to 114% increase in for peroxidase, 21.3% to 59.7% increase in phenylalanine ammonia-lyase and 5.8 to 19.5 fold in ascorbate specific peroxidase was observed. However, biomass and height of conventional cotton seedlings were not affected by any concentration of transgenic cotton root exudates. These results suggested that cultivation of transgenic Bt+CpTI cotton plants poses little risk to conventional parental cotton based on their root interactions.

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

BACKGROUND: Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. METHODS: A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. RESULTS: Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. CONCLUSIONS: In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors.

Distribution and environmental significance of nitrite-dependent anaerobic methane-oxidising bacteria in natural ecosystems.

Nitrite-dependent anaerobic methane oxidation (N-DAMO) is a recently discovered process that is performed by "Candidatus Methylomirabilis oxyfera" (M. oxyfera). This process constitutes a unique association between the two major global elements essential to life, carbon and nitrogen, and may act as an important and overlooked sink of the greenhouse gas methane. In recent years, more and more studies have reported the distribution of M. oxyfera-like bacteria and the occurrence of N-DAMO process in different natural ecosystems, including freshwater lakes, rivers, wetlands and marine ecosystems. Previous studies have estimated that a total of 2%-6% of current worldwide methane flux in wetlands could be consumed via the N-DAMO process. These findings indicate that N-DAMO is indeed a previously overlooked methane sink in natural ecosystems. Given the worldwide increase in anthropogenic nitrogen pollution, the N-DAMO process as a methane sink in reducing global warming could become more important in the future. The present mini-review summarises the current knowledge of the ecological distribution of M. oxyfera-like bacteria and the potential importance of the N-DAMO process in reducing methane emissions in various natural ecosystems. The potential influence of environmental factors on the N-DAMO process is also discussed.

Occurrence and importance of anaerobic ammonium-oxidising bacteria in vegetable soils.

The quantitative importance of anaerobic ammonium oxidation (anammox) has been described in paddy fields, while the presence and importance of anammox in subsurface soil from vegetable fields have not been determined yet. Here, we investigated the occurrence and activity of anammox bacteria in five different types of vegetable fields located in Jiangsu Province, China. Stable isotope experiments confirmed the anammox activity in the examined soils, with the potential rates of 2.1 and 23.2 nmol N2 g(-1) dry soil day(-1), and the anammox accounted for 5.9-20.5% of total soil dinitrogen gas production. It is estimated that a total loss of 7.1-78.2 g N m(-2) year(-1) could be linked to the anammox process in the examined vegetable fields. Phylogenetic analyses showed that multiple co-occurring anammox genera were present in the examined soils, including Candidatus Brocadia, Candidatus Kuenenia, Candidatus Anammoxoglobus and Candidatus Jettenia, and Candidatus Brocadia appeared to be the most common anammox genus. Quantitative PCR further confirmed the presence of anammox bacteria in the examined soils, with the abundance varying from 2.8 × 10(5) to 3.0 × 10(6) copies g(-1) dry soil. Correlation analyses suggested that the soil ammonium concentration had significant influence on the activity and abundance of anammox bacteria in the examined soils. The results of our study showed the presence of diverse anammox bacteria and indicated that the anammox process could serve as an important nitrogen loss pathway in vegetable fields.

Transcriptome responses to heat- and cold-stress in ladybirds (Cryptolaemus montrouzieri Mulasnt) analyzed by deep-sequencing.

BACKGROUND: Changed temperature not only threaten agricultural production, but they also affect individual biological behavior, population and community of many insects, and consequently reduce the stability of our ecosystem. Insect's ability to respond to temperature stress evolved through a complex adaptive process, thus resulting in varied temperature tolerance among different insects. Both high and low extreme temperatures are detrimental to insect development since they constitute an important abiotic stress capable of inducing abnormal biological responses. Many studies on heat or cold tolerance of ladybirds have focused on measurements of physiological and biochemical indexes such as supercooling point, higher/lower lethal temperatures, survival rate, dry body weight, water content, and developmental duration. And studies of the molecular mechanisms of ladybird responses to heat or cold stress have focused on single genes, such as those encoding heat shock proteins, but has not been analyzed by transcriptome profiling. RESULTS: In this study, we report the use of Digital Gene Expression (DGE) tag profiling to gain insight into transcriptional events associated with heat- and cold-stress in C. montrouzieri. About 6 million tags (49 bp in length) were sequenced in a heat stress group, a cold stress group and a negative control group. We obtained 687 and 573 genes that showed significantly altered expression levels following heat and cold shock treatments, respectively. Analysis of the global gene expression pattern suggested that 42 enzyme-encoding genes mapped to many Gene Ontology terms are associated with insect's response to heat- and cold-stress. CONCLUSIONS: These results provide a global assessment of genes and molecular mechanisms involved in heat and cold tolerance.

Nitrite-dependent anaerobic methane-oxidising bacteria: unique microorganisms with special properties.

Microbial mediated nitrite-dependent anaerobic methane oxidation (N-DAMO), which couples the oxidation of methane to nitrite reduction, is a recently discovered process. The discovery of N-DAMO process makes great contributions to complete the biogeochemical cycles of carbon and nitrogen, and to develop novel economic biotechnology for simultaneous carbon and nitrogen removal. This process is catalysed by the unique bacterium "Candidatus Methylomirabilis oxyfera" (M. oxyfera), which belongs to the candidate phylum NC10, a phylum having no members in pure culture. In recent years, some microbiological properties of M. oxyfera have been unravelled. The most prominent examples are the discoveries of the special ultrastructure (star-like) of the cell shape and the unique chemical composition (10MeC16:1Δ7) of M. oxyfera that have not been found in other bacteria yet. More importantly, a new intra-aerobic pathway was discovered in M. oxyfera. It seems that M. oxyfera produces oxygen intracellularly by the conversion of two nitric oxide molecules to dinitrogen gas and oxygen, and the produced oxygen is then used for methane oxidation and normal respiration. The current paper is a systematic review in the microbiological properties of M. oxyfera, especially for its special properties.

Predictive value of the neutrophil-to-lymphocyte ratio in the prognosis and risk of death for adult sepsis patients: a meta-analysis.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator for clinical practice. However, no consensus has been reached on the prognostic value of NLR for predicting the prognosis and mortality risk in adult sepsis patients. In light of this controversy, we conducted a meta-analysis to clarify the prognostic significance of NLR in adult sepsis patients. The meta-analysis was registered in the PROSPERO database (registration number CRD42023433143). Methods: We performed a comprehensive literature search in PubMed, Cochrane Library, Ovid, and Springer databases, using retrieval terms "sepsis" or "septic shock" and "prognosis" or "mortality" for studies published between January 1, 2000, and May 31, 2023. Children and neonates with sepsis were excluded from our research. Two independent researchers conducted the literature search and data extraction. Consensus was reached when discrepancies occurred, and in case of persistent discrepancies, the final decision was made by the research supervisor. The hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were extracted from each study included in the analysis. A random-effects model was used to synthesize all HRs and their 95% CIs. Sensitivity analysis was performed to investigate heterogeneity. Sensitivity analysis was conducted to identify studies that had a significant impact on the overall results of the meta-analysis. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Egger's test was also used to investigate publication bias in this meta-analysis. Results: After a comprehensive literature search and screening, we included 12 studies comprising 10,811 patients for the meta-analysis. The pooled results indicated that patients with a higher NLR level were associated with a poor prognosis (Random-effects model, HR: 1.6273, 95% CI: 1.3951-1.8981). Heterogeneity testing showed significant heterogeneity (I2 = 87.2%, 95% CI: 79.5-92, p<0.0001). Sensitivity analysis was performed to investigate the sources of heterogeneity, which revealed that the omission of one highly sensitive study significantly reduced the I2 value. After removing this study, a strong association was found between a higher NLR level and poor prognosis and risk of death in adult sepsis patients (Random-effects model, HR: 1.6884, 95% CI: 1.4338-1.9882). Both subgroup analysis and meta-regression indicated that the study design and testing time of NLR were sources of heterogeneity. Egger's test showed no obvious publication bias in this meta-analysis. Conclusion: NLR is a reliable and valuable biomarker for predicting prognosis and the risk of death in adult sepsis patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433143] PROSPERO, identifier [CRD42023433143].

Retraction notice to "A nomogram for predicting in-hospital overall survival of hypertriglyceridemia-induced severe acute pancreatitis: A single center, cross-sectional study" [HLY 10 (2023) e23454].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e23454.].

A nomogram for predicting in-hospital overall survival of hypertriglyceridemia-induced severe acute pancreatitis: A single center, cross-sectional study.

Background: Hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) is a type of pancreatitis characterized by an abnormal elevation of plasma triglyceride. HTG-SAP has been associated with various complications and a high mortality rate. In this study, we established a nomogram for predicting the overall survival (OS) of HTG-SAP patients during hospitalization. Methods: 128 HTG-SAP cases hospitalized at the Affiliated Huadu Hospital, Southern Medical University, from 2019 to 2022 were analyzed retrospectively. A nomogram including prognostic factors correlated with OS during hospitalization was established by multivariate Cox regression analysis. We internally validated the nomogram using time-dependent (at 1-, 2-, and 3- months) survival receiver operating characteristic (SROC) and calibration curve with 500 iterations of bootstrap resampling. Time-dependent decision curve analysis (DCA) was employed to validate the clinical value of the nomogram. Results: Multivariate Cox regression indicated that serum triglyceride, red blood cell distribution width (RDW), lactic acid, and interleukin-6 (IL6) were independent prognostic factors for OS of HTG-SAP patients during hospitalization and were used to construct a nomogram. The time-dependent area under the curve (AUC) values at 1-, 2-, and 3- months were 0.946, 0.913, and 0.929, respectively, and the Concordance index (C-index) of the nomogram was 0.916 (95%CI 0.871-0.961). The time-dependent calibration curves indicated good consistency between the observed and predicted outcomes. The time-dependent DCAs also revealed that the nomogram yielded a high clinical net benefit. After stratifying the included cases into two risk groups based on the risk score obtained from the nomogram, the high-risk group exhibited a significantly inferior overall survival (OS) compared to the low-risk group (p < 0.0001). Conclusions: Our nomogram exhibited good performance in predicting the overall survival of HTG-SAP patients during hospitalization.

Establishment of a mortality risk nomogram for predicting in-hospital mortality of sepsis: cohort study from a Chinese single center.

Objective: To establish a mortality risk nomogram for predicting in-hospital mortality of sepsis patients in the Chinese population. Methods: Data were obtained from the medical records of sepsis patients enrolled at the Affiliated Huadu Hospital, Southern Medical University, between 2019 and 2021. A total of 696 sepsis patients were initially included in our research, and 582 cases were finally enrolled after screening and divided into the survival group (n = 400) and the non-survival group (n = 182) according to the incidence of mortality during hospitalization. Twenty-eight potential sepsis-related risk factors for mortality were identified. Least absolute shrinkage and selection operator (LASSO) regression was used to optimize variable selection by running cyclic coordinate descent with k-fold (tenfold in this case) cross-validation. We used binary logistic regression to build a model for predicting mortality from the variables based on LASSO regression selection. Binary logistic regression was used to establish a nomogram based on independent mortality risk factors. To validate the prediction accuracy of the nomogram, receiver operating characteristic curve (ROC) analysis, decision curve analysis (DCA) and restricted cubic spline (RCS) analysis were employed. Eventually, the Hosmer-Lemeshow test and calibration curve were used for nomogram calibration. Results: LASSO regression identified a total of ten factors, namely, chronic heart disease (CHD), lymphocyte count (LYMP), neutrophil-lymphocyte ratio (NLR), red blood cell distribution width (RDW), C reactive protein (CRP), Procalcitonin (PCT), lactic acid, prothrombin time (PT), alanine aminotransferase (ALT), total bilirubin (Tbil), interleukin-6 (IL6), that were incorporated into the multivariable analysis. Finally, a nomogram including CHD, LYMP, NLR, RDW, lactic acid, PT, CRP, PCT, Tbil, ALT, and IL6 was established by multivariable logistic regression. The ROC curves of the nomogram in the training and validation sets were 0.9836 and 0.9502, respectively. DCA showed that the nomogram could be applied clinically if the risk threshold was between 29.52 and 99.61% in the training set and between 31.32 and 98.49% in the testing set. RCS showed that when the value of independent risk factors from the predicted model exceeded the median, the mortality hazard ratio increased sharply. The results of the Hosmer-Lemeshow test (χ2 = 0.1901, df = 2, p = 0.9091) and the calibration curves of the training and validation sets showed good agreement with the actual results, which indicated good stability of the model. Conclusion: Our nomogram, including CHD, LYMP, NLR, RDW, lactic acid, PT, CRP, PCT, Tbil, ALT, and IL6, exhibits good performance for predicting mortality risk in adult sepsis patients.

Immune effector dysfunction signatures predict outcomes in patients with colorectal cancer.

BACKGROUND: Immune effector dysfunction (IED) is mainly manifested as immune exhaustion and senescence, which are the primary obstacles to the success of cancer immunotherapy. In the current study, we characterized the prognostic relevance of IED signatures in patients with colorectal cancer (CRC). METHODS: Immunohistochemistry (IHC) data of CRC tissue samples from 41 newly diagnosed patients in our clinical center (HDPH cohort) were used to investigate the prognostic importance of IED signatures. The results were validated by the RNA sequencing data of 372 CRC patients from the Cancer Genome Atlas (TCGA) database. RESULTS: In the HDPH cohorts, high Natural Killer (NK) and CD8+ tumor-infiltrating lymphocytes (TILs) were associated with poor overall survival (OS) and relapse-free survival (RFS) in CRC patients. Optimal IED signatures, including high expression of CCR9, ISG20, and low expression of ICOS, and CACNA2D2, predicted poor OS and RFS. Moreover, high-risk scores estimated by a weighted combination of these four IED genes were associated with poor OS and RFS. Notably, risk stratification was constructed by combining risk score and tumor node metastasis (TNM) stage better than TNM stage alone in predicting OS and RFS for CRC patients. The above results were confirmed in the TCGA cohort. CONCLUSION: CCR9, ISG20, ICOS, and CACNA2D2 were optimal IED signatures for predicting the outcomes of CRC patients, which might be a potential biomarker for prognostic stratification and designing novel CRC therapy.