Table_1_v1_High Body Mass Index Is Associated with an Increased Risk of the Onset and Severity of Ossification of Spinal Ligaments.docx

BackgroundOssification of the posterior longitudinal ligament (OPLL) and that of ligamentum flavum (OLF) are the main types of the ossification of spinal ligaments (OSL) that cause the thoracic myelopathy. Although several studies have investigated the relationship of body mass index (BMI) with the onset or severity of OSL, it remains unverified due to the contradictory results of existing evidence. A systematic review and meta-analysis were performed in this work to determine the relationship of BMI with the onset and severity of OSL.MethodsPubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched online for relevant studies focusing on the relationship of BMI with the onset or severity of the OSL. The difference in BMI of OSL (or severe OSL group) and non-OSL (or nonsevere OSL group) groups was evaluated using the mean difference (MD) with a corresponding 95% confidence interval (CI).ResultsFifteen studies were included in this systematic review and meta-analysis. The BMI of the OSL group was significantly higher than that of the non-OSL group (MD = 1.70 kg/m2, 95% CI = 1.02–2.39 kg/m2, and P 2, and P = 0.04).ConclusionThe significant association of high BMI with the onset and severity of OSL may provide new evidence and insights into the mechanism research and management of OSL.</p

Table_2_v1_High Body Mass Index Is Associated with an Increased Risk of the Onset and Severity of Ossification of Spinal Ligaments.docx

BackgroundOssification of the posterior longitudinal ligament (OPLL) and that of ligamentum flavum (OLF) are the main types of the ossification of spinal ligaments (OSL) that cause the thoracic myelopathy. Although several studies have investigated the relationship of body mass index (BMI) with the onset or severity of OSL, it remains unverified due to the contradictory results of existing evidence. A systematic review and meta-analysis were performed in this work to determine the relationship of BMI with the onset and severity of OSL.MethodsPubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched online for relevant studies focusing on the relationship of BMI with the onset or severity of the OSL. The difference in BMI of OSL (or severe OSL group) and non-OSL (or nonsevere OSL group) groups was evaluated using the mean difference (MD) with a corresponding 95% confidence interval (CI).ResultsFifteen studies were included in this systematic review and meta-analysis. The BMI of the OSL group was significantly higher than that of the non-OSL group (MD = 1.70 kg/m2, 95% CI = 1.02–2.39 kg/m2, and P 2, and P = 0.04).ConclusionThe significant association of high BMI with the onset and severity of OSL may provide new evidence and insights into the mechanism research and management of OSL.</p

DataSheet1_Risk of infection in roxadustat treatment for anemia in patients with chronic kidney disease: A systematic review with meta-analysis and trial sequential analysis.docx

Background: Many studies demonstrated that roxadustat (FG-4592) could increase hemoglobin (Hb) levels effectively in anemia patients with chronic kidney disease (CKD). However, its safety remains controversial. This study aims to explore the risk of infection for CKD patients treated with roxadustat, especially focused on sepsis.Methods: We thoroughly searched for the randomized controlled trials (RCTs) comparing treatment with roxadustat versus erythropoiesis stimulating agents (ESAs) or placebo in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, European Union Clinical Trials Register. Both on and not on dialysis anemia patients with CKD were included. Primary outcomes contained the incidence rates of sepsis. Secondary outcomes included infection-related consequences (septic shock and other infection events), general safety outcomes [all-cause mortality, treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)] and iron parameters. Moreover, a trial sequential analysis (TSA) was conducted to assess if the results were supposed to be a robust conclusion.Results: Eighteen RCTs (n = 11,305) were included. Overall, the incidence of sepsis (RR: 2.42, 95% CI [1.50, 3.89], p = 0.0003) and cellulitis (RR: 2.07, 95% CI [1.24, 3.44], p = 0.005) were increased in the roxadustat group compared with placebo group. In non-dialysis-dependent (NDD) CKD patients, the incidence of cellulitis (RR 2.01, 95% CI [1.23, 3.28], p = 0.005) was significantly higher in roxadustat group than that in the ESAs or placebo group. Both groups showed similar results in the incidence of septic shock (RR 1.29, 95% CI [0.86, 1.94], p = 0.22). A significant increased risk of all-cause mortality [risk ratios (RR): 1.15, 95% confidence interval (CI) [1.05, 1.26], p = 0.002] was found in roxadustat treatment, and TSA confirmed the result. Compared with ESAs or placebo, both the incident rates of TEAEs (RR:1.03, 95% CI [1.01, 1.04], p = 0.008) and TESAEs (RR: 1.06, 95% CI [1.02, 1.11], p = 0.002) were significantly increased in roxadustat group. As for iron parameters, changes from baseline (Δ) of hepcidin (MD: -26.46, 95% CI [-39.83, -13.09], p = 0.0001), Δ ferritin and Δ TSAT were remarkably lower in the roxadustat group, while Δ Hb, Δ iron and Δ TIBC increased significantly versus those in ESAs or placebo group.Conclusion: We found evidence that incidence rates of sepsis and cellulitis are higher in roxadustat group compared with placebo. This may be the result of improved iron homeostasis. The risk of all-cause mortality, TEAEs and TESAEs in CKD patients also increased in patients treated with roxadustat. We need more clinical and mechanistic studies to confirm whether roxadustat really causes infection.</p

Microbial Multitrophic Communities Drive the Variation of Antibiotic Resistome in the Gut of Soil Woodlice (Crustacea: Isopoda)

Multitrophic communities inhabit in soil faunal gut, including bacteria, fungi, and protists, which have been considered a hidden reservoir for antibiotic resistance genes (ARGs). However, there is a dearth of research focusing on the relationships between ARGs and multitrophic communities in the gut of soil faunas. Here, we studied the contribution of multitrophic communities to variations of ARGs in the soil woodlouse gut. The results revealed diverse and abundant ARGs in the woodlouse gut. Network analysis further exhibited strong connections between key ecological module members and ARGs, suggesting that multitrophic communities in the keystone ecological cluster may play a pivotal role in the variation of ARGs in the woodlouse gut. Moreover, long-term application of sewage sludge significantly altered the woodlice gut resistome and interkingdom communities. The variation portioning analysis indicated that the fungal community has a greater contribution to variations of ARGs than bacterial and protistan communities in the woodlice gut after long-term application of sewage sludge. Together, our results showed that changes in gut microbiota associated with agricultural practices (e.g., sewage sludge application) can largely alter the gut interkingdom network in ecologically relevant soil animals, with implications for antibiotic resistance, which advances our understanding of the microecological drivers of ARGs in terrestrial ecosystem

Table1_Hematologic side effects of immune checkpoint inhibitor with or without chemotherapy in patients with advanced and metastatic gastrointestinal cancer: A systematic review and network meta-analysis of phase 3 trials.DOCX

Background: The regimens of immune checkpoint inhibitors (ICIs) alone or with chemotherapy are emerging as systemic therapy for patients with advanced and metastatic gastrointestinal cancers. However, the risk of treatment-related hematologic toxicity stays unclear.Methods: We enrolled in phase 3 randomized clinical trials (RCTs) comparing PD-1, PD-L1, and CTLA-4 inhibitors in advanced and metastatic gastrointestinal cancers. The incidences of overall treatment-related adverse events (TRAEs), discontinuation, leukopenia, neutropenia, thrombocytopenia, and anemia were extracted for the Bayesian network meta-analysis. Analyses with poor convergence or low incidence were reported as incidences with 95% CIs instead.Results: Sixteen phase 3 RCTs with 9732 patients who received systemic therapy were included. A total of 150 (1.54% [95% CI 1.31–1.80]) treatment-related death events were recorded, whereas 13 (0.13% [95% CI 0.08–0.22]) of them were hematologic. 0.24% (95% CI 0.12–0.48) patients received ICI plus chemotherapy were recorded for hematological deaths, 0.09% (95% CI 0.01–0.23) were for chemotherapy alone, and 0.05% were for ICI alone (95% CI 0.01–0.29). Febrile neutropenia was the most frequent cause of death in ICI with chemotherapy. For grade ≥3 TRAEs, we found nivolumab plus chemotherapy (OR 1.63 [95% CI 0.84–3.17]) had a higher risk than other treatments. Overall, ICI monotherapy led to fewer AEs than chemotherapy-based regimens in the analyses of leukopenia, neutropenia, thrombocytopenia, and anemia. Among the 11 treatments, toripalimab plus chemotherapy possessed the highest risk in any-grade leukopenia (OR 1.84 [95% CI 0.48, 6.82]) and neutropenia (OR 1.71 [95% CI 0.17, 17.40]) respectively. For grade ≥3 hematologic AEs, neutropenia (20.08% [95% CI 18.67–21.56]) related to ICI plus chemotherapy was the most dominant. ICI plus chemotherapy was likely to increase the incidence than dosing these drugs alone.Conclusion: Using ICI alone had a low incidence of causing hematologic mortality and AEs, while the combination with chemotherapy might magnify the side effects. Comprehensively, pembrolizumab plus chemotherapy and sintilimab plus chemotherapy were the safest regimens in terms of leukopenia and neutropenia respectively. This study will guide clinical practice for ICI-based chemotherapy.Systematic Review Registration: PROSPERO, identifier CRD42022380150</p

Magnetic nanoparticles modified with quaternarized <i>N</i>-halamine based polymer and their antibacterial properties

<p>We present a simple and facile approach for preparing antibacterial magnetic nanoparticles, which were modified with quaternarized <i>N</i>-halamine based cationic polymer (CPQN). The CPQN functionalized magnetic nanoparticles (MNPs-CPQN) were characterized by X-ray photoelectron spectra, Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, and thermogravimetric analysis. Antibacterial properties were investigated with Gram positive bacteria <i>S. aureus</i> and Gram negative bacteria <i>E. coli</i>. Antibacterial assessment showed that the MNPs-CPQN could eliminate nearly 100% of <i>S. aureus</i> and 99.9% of <i>E. coli</i> (10^7-8 CFU/mg nanoparticles) in 5 min, while the bactericide rate of quaternized <i>N</i>-halamine precursor based cationic polymer coated magnetic nanoparticles (MNPs-CPQNP) were 99.6 and 95.2%, respectively. The prepared nanoparticles exhibited a good response to an external magnetic field and had a saturation magnetization of 36.6 emu g⁻¹. On the basis of their excellent antibacterial properties and magnetic responsiveness, the MNPs-CPQN would be a promising antibacterial material for water disinfection.</p

Missing value imputation for microarray gene expression data using histone acetylation information-2

Er random model of missing values. The horizontal axis is the varying range of missing percentages from 1% to 20%. The vertical axis is Pearson correlation coefficients of 100 independent and random test runs for each method. We observed that the results are consistent with the NRMSE performances in Figure 1 across the whole test missing percentages. The genes imputed by llsHAI are most correlated with the original complete genes while the genes imputed by knnHAI are more correlated with the original complete genes than those imputed by KNN.<p><b>Copyright information:</b></p><p>Taken from "Missing value imputation for microarray gene expression data using histone acetylation information"</p><p>http://www.biomedcentral.com/1471-2105/9/252</p><p>BMC Bioinformatics 2008;9():252-252.</p><p>Published online 29 May 2008</p><p>PMCID:PMC2432074.</p><p></p

Additional file 5 of Co-expression and prognosis analyses of GLUT1–4 and RB1 in breast cancer

Additional file 5: Figure S5. Negative results of the correlation analyses in LinkedOmic