Antibody-free profiling of transcription factor occupancy during early embryogenesis by FitCUT&RUN.

Key transcription factors (TFs) play critical roles in zygotic genome activation (ZGA) during early embryogenesis, whereas genome-wide occupancies of only a few factors have been profiled during ZGA due to the limitation of cell numbers or the lack of high-quality antibodies. Here, we present FitCUT&RUN, a modified CUT&RUN method, in which an Fc fragment of immunoglobulin G is used for tagging, to profile TF occupancy in an antibody-free manner and demonstrate its reliability and robustness using as few as 5000 K562 cells. We applied FitCUT&RUN to zebrafish undergoing embryogenesis to generate reliable occupancy profiles of three known activators of zebrafish ZGA: Nanog, Pou5f3, and Sox19b. By profiling the time-series occupancy of Nanog during zebrafish ZGA, we observed a clear trend toward a gradual increase in Nanog occupancy and found that Nanog occupancy prior to the major phase of ZGA is important for the activation of some early transcribed genes.

Characterization of H3K9me3 and DNA methylation co-marked CpG-rich regions during mouse development.

BACKGROUND: H3K9me3 and DNA methylation co-marked CpG-rich regions (CHMs) are functionally important in mouse pre-implantation embryos, but their characteristics in other biological processes are still largely unknown. RESULTS: In this study, we performed a comprehensive analysis to characterize CHMs during 6 mouse developmental processes, identifying over 2,600 CHMs exhibiting stable co-mark of H3K9me3 and DNA methylation patterns at CpG-rich regions. We revealed the distinctive features of CHMs, including elevated H3K9me3 signals and a significant presence in euchromatin and the potential role in silencing younger long terminal repeats (LTRs), especially in some ERVK subfamilies. The results highlight the distinct nature of universal CHMs compared to CpG-rich nonCHMs in terms of location, LTR enrichment, and DNA sequence features, enhancing our understanding of CpG-rich regions' regulatory roles. CONCLUSIONS: This study characterizes the features of CHMs in multiple developmental processes and broadens our understanding of the regulatory roles of CpG-rich regions.

Age and gender differences in symptom experience and health-related quality of life in kidney transplant recipients: a cross-sectional study.

BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. METHODS: Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. RESULTS: A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7-22), with a burden of 20 (8-37; range 0-244). Per extra symptom, physical and mental HRQOL decreased [-0.41 (-0.50; -0.31) and -0.51 (-0.59; -0.42), respectively, P < .001]. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18-50 > 50-65 ≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. CONCLUSION: KRTs' symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.

Understanding Health-Related Quality of Life in Kidney Transplant Recipients: The Role of Symptom Experience and Illness Perceptions.

The purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions mediated this impact. Symptom experience, illness perceptions, and HRQOL were measured at transplantation and 6 weeks after transplantation in KTRs in an ongoing Dutch cohort study. Multivariable linear regression models were used for the analysis. 90 KTRs were analyzed. Fatigue and lack of energy were the most prevalent and burdensome symptoms at transplantation. Mental HRQOL at 6 weeks after transplantation was comparable to that of the general Dutch population (mean [standard deviation, SD]: 49.9 [10.7]) versus 50.2 [9.2]), while physical HRQOL was significantly lower (38.9 [9.1] versus 50.6 [9.2]). Experiencing more symptoms was associated with lower physical and mental HRQOL, and the corresponding HRQOL reduced by -0.15 (95%CI, -0.31; 0.02) and -0.23 (95%CI, -0.42; -0.04) with each additional symptom. The identified mediation effect suggests that worse symptom experiences could cause more unhelpful illness perceptions and consequently lead to lower HRQOL. Illness perceptions may explain the negative impact of symptom experience on HRQOL. Future studies at later stages after kidney transplantation are needed to further explore the mediation effect of illness perceptions and guide clinical practice to improve HRQOL.

Illness Perceptions and Medication Nonadherence to Immunosuppressants After Successful Kidney Transplantation: A Cross-Sectional Study.

Background: Medication nonadherence to immunosuppressants is a well-known risk factor for suboptimal health outcomes in kidney transplant recipients (KTRs). This study examined the relationship between illness perceptions and medication nonadherence in prevalent Dutch KTRs and whether this relationship depended on post-transplant time. Methods: Eligible KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. The illness perceptions and medication nonadherence were measured via validated questionnaires. Associations between illness perceptions and medication nonadherence were investigated using multivariable logistic regression models. Results: For the study, 627 participating KTRs were analyzed. 203 (32.4%) KTRs were considered nonadherent to their immunosuppressants with "taking medication more than 2 h from the prescribed dosing time" as the most prevalent nonadherent behaviour (n = 171; 27.3%). Three illness perceptions were significantly associated with medication nonadherence: illness identity (adjusted odds ratio [ORadj] = 1.07; 95% confidence interval [CI], 1.00-1.14), concern (ORadj = 1.07; 95%CI,1.00-1.14), and illness coherence (ORadj = 1.11; 95%CI,1.01-1.22). The relationships between illness perceptions and medication nonadherence did not differ depending on post-transplant time (p-values ranged from 0.48 to 0.96). Conclusion: Stronger negative illness perceptions are associated with medication nonadherence to immunosuppressants. Targeting negative illness perceptions by means of psychoeducational interventions could optimize medication adherence and consequently improve health outcomes in KTRs.

Electropolymerization of Metal Clusters Establishing a Versatile Platform for Enhanced Catalysis Performance.

Atomically precise metal clusters are attractive as highly efficient catalysts, but suffer from continuous efficiency deactivation in the catalytic process. Here, we report the development of an efficient strategy that enhances catalytic performance by electropolymerization (EP) of metal clusters into hybrid materials. Based on carbazole ligand protection, three polymerized metal-cluster hybrid materials, namely Poly-Cu14 cba, Poly-Cu6 Au6 cbz and Poly-Cu6 Ag4 cbz, were prepared. Compared with isolated metal clusters, metal clusters immobilizing on a biscarbazole network after EP significantly improved their electron-transfer ability and long-term recyclability, resulting in higher catalytic performance. As a proof-of-concept, Poly-Cu14 cba was evaluated as an electrocatalyst for reducing nitrate (NO3 - ) to ammonia (NH3 ), which exhibited ≈4-fold NH3 yield rate and ≈2-fold Faraday efficiency enhancement compared to that of Cu14 cba with good durability. Similarly, Poly-Cu6 Au6 cbz showed 10 times higher photocatalytic efficiency towards chemical warfare simulants degradation than the cluster counterpart.

Mapping health-related quality of life after kidney transplantation by group comparisons: a systematic review.

BACKGROUND: Health-related quality of life (HRQOL) is becoming an increasingly important outcome in kidney transplantation (KT). To describe HRQOL in kidney transplant recipients (KTRs), this systematic review summarizes literature that compared HRQOL among KTRs and other relevant populations [i.e. patients receiving dialysis, patients on the waiting list (WL) for KT, patients with chronic kidney disease (CKD) not receiving renal replacement therapy (RRT), the general population (GP) and healthy controls (HCs)] and themselves before KT. METHODS: The literature search was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Eligible studies published between January 2000 and October 2020 were included. RESULTS: Forty-four studies comprising 6929 KTRs were included in this systematic review. Despite the study heterogeneity, KTRs reported a higher HRQOL after KT compared with pre-transplantation and compared with patients receiving dialysis with or without being on the WL, especially in disease-specific domains (i.e. burden and effects of kidney disease). Additionally, KTRs had similar to marginally higher HRQOL compared with patients with CKD Stages 3-5 not receiving RRT. When compared with HCs or the GP, KTRs reported similar HRQOL in the first 1 or 2 years after KT and lower physical HRQOL and lower to comparable mental HRQOL in studies with longer post-transplant time. CONCLUSIONS: The available evidence suggests that HRQOL improves after KT and can be restored to but not always maintained at pre-CKD HRQOL levels. Future studies investigating intervention targets to improve or maintain post-transplant HRQOL are needed.

Donor type and 3-month hospital readmission following kidney transplantation: results from the Netherlands organ transplant registry.

BACKGROUND: Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs. METHODS: We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders. RESULTS: Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly. CONCLUSION: A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.

FTY720 Attenuates Angiotensin II-Induced Podocyte Damage via Inhibiting Inflammatory Cytokines.

FTY720, a new chemical substance derived from the ascomycete Isaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease. In this study, we selected 40 patients with IgA nephropathy and examined their clinical characteristics. Ang II-infusion rat renal injury model was established to evaluate the glomeruli and tubulointerstitial lesion. The result showed that the concentration of S1P in serum and urine was positively correlated with IgA nephropathy patients' renal injury. FTY720 could reduce renal histological lesions induced by Ang II-infusion in rats. Moreover, FTY720 decreased S1P synthesis in Ang II-infusion rats via downregulation of inflammatory cytokines including TNF-α and IL-6. In addition, FTY720 alleviated exogenous S1P-induced podocyte damage. In conclusion, FTY720 is able to attenuate S1P-induced podocyte damage via reducing inflammatory cytokines.

Finite-time synchronization for coupled neural networks with time-delay jumping coupling.

The finite-time synchronization problem is studied for coupled neural networks (CNNs) with time-delay jumping coupling. Markovian switching topologies, imprecise delay models, uncertain parameters and the unavailable of topology modes are considered in this work. A mode-dependent delay with pre-known conditional probability is built to handle the imprecise delay model problem. A hidden Markov model with uncertain parameters is introduced to describe the mode mismatch problem, and an asynchronous controller is designed. Besides, a set of Bernoulli processes models the random packet dropouts during data communication. Based on Markovian switching topologies, mode-dependent delays, uncertain probabilities and packet dropout, a sufficient condition that guarantees the CNNs reach finite-time synchronization (FTS) is derived. Finally, a numerical example is derived to demonstrate the efficiency of the proposed synchronous technique.

Asymmetrical Interactions between Ni Single Atomic Sites and Ni Clusters in a 3D Porous Organic Framework for Enhanced CO2 Photoreduction.

3D porous organic frameworks, which possess the advantages of high surface area and abundant exposed active sites, are considered ideal platforms to accommodate single atoms (SAs) and metal nanoclusters (NCs) in high-performance catalysts; however, very little research has been conducted in this field. In the present work, a 3D porous organic framework containing Ni1 SAs and Nin NCs is prepared through the metal-assisted one-pot polycondensation of tetraaldehyde and hexaaminotriptycene. The single metal sites and metal clusters confined in the 3D space created a favorable micro-environment that facilitated the activation of chemically inert CO2 molecules, thus promoting the overall photoconversion efficiency and selectivity of CO2 reduction. The 3D-NiSAs/NiNCs-POPs, as a CO2 photoreduction catalyst, demonstrated an exceptional CO production rate of 6.24 mmol g-1 h-1, high selectivity of 98%, and excellent stability. The theoretical calculations uncovered that asymmetrical interaction between Ni1 SAs and Nin NCs not only favored the bending of CO2 molecules and reducing the CO2 reduction energy, but also regulated the electronic structure of the catalyst leading to the optimal binding strength of intermediates.

Isolation and analysis of the exosomal membrane proteins in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a severe autoimmune sub-epidermal bullous disease. Exosomes are small extracellular vesicles secreted by most cell types. The exosomal membrane proteins are implicated in various biological and pathological pathways. This study aims to explore the potential roles of exosomes in BP pathomechanism. RESEARCH DESIGN: We collected plasma samples from 30 BP patients and 31 healthy controls. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of exosomes. The immunogold labelling experiment and extracellular vesicle (EV) array were performed to detect the content and distribution of exosomes. RESULTS: The exosomes from both the BP and control groups' plasma were successfully extracted. EV Array showed that CD63 and CD9 levels were significantly higher in the BP group than in the control group (p < 0.05). Expression levels of the BP180 NC16A and intracellular domain (ICD) were higher in the anti-BP180 positive group versus the controls (p < 0.05). The active BP group exhibits higher CD63 and BP180 ICD protein concentrations than the control or inactive BP groups (p < 0.05). CONCLUSION: BP180 autoantigen fragments were expressed on the exosomal membrane in BP patients. The BP180 ICD and CD63 on exosomes could potentially be novel biomarkers for monitoring disease activity.

Single-atom tailored atomically-precise nanoclusters for enhanced electrochemical reduction of CO2-to-CO activity.

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters catalysts is of great interest but remians challenging. Herein, the well-defined Au8 nanoclusters modified by single-atom sites are rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal nanocluster and single-atom co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing single-atoms enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic reduction of CO2 to CO activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2 reduction reaction. Moreover, this strategy fixing nanoclusters and single-atoms on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.

Dip-transfer phosphor coating on designed substrate structure for high angular color uniformity of white light emitting diodes with conventional chips.

Angular color uniformity (ACU) is one of the most important optical parameters of white lighting emitting diodes (LEDs). In this paper, we proposed a kind of phosphor coating method to enhance ACU of phosphor-converted white LEDs with conventional chips by the combination of substrate structure design and phosphor dip-transfer coating. Through this method, compact and optimal phosphor layer arrangements for high ACU can be realized. Optical simulations and experiments were conducted to examine its ACU performance. Compared with conventional phosphor dispensing coating, the present method shows very high ACU performance. Extremely small angular correlated color temperature (CCT) deviations were obtained, which are less than 200K at average CCTs ranging from 4000 K to 6000 K.

Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid.

Aim: Bullous pemphigoid (BP) is an organ-specific autoimmune bullous disease characterized by autoantibodies that target the cellular adhesion molecules BP180 and BP230. Both immunoglobulin (Ig)G and IgE are involved in the induction of subepidermal blisters. Specifically, IgE autoantibodies are presumed to be responsible for the pruritic and erythematous features of BP. Histologically, eosinophil infiltration is a prominent feature in BP. Eosinophils and IgE are mostly associated with the Th2 immune response. Th2 cytokines, particularly interleukin (IL)-4 and IL-13, are presumed to contribute to the pathology of BP. The aim of this review is to discuss the role of IL-4/13 in the pathogenesis of BP and the potential of using IL-4/13 antagonists for treatment.Methods: After searching in PubMed and Web of Science databases using 'bullous pemphigoid', 'interleukin-4/13', and 'dupilumab' as keywords, studies related was compiled and examined.Results: Overall, IgE, eosinophils, IL-4, and IL-13 may interact with each other in the pathogenesis of BP; these potential interactions provide clues concerning targets for molecular treatment.Conclusion: Anti-IL-4/13 treatment has been experimentally used in patients with BP, with satisfactory outcomes and few side effects. However, before this novel therapy can be approved for regular usage, further studies are needed concerning the long-term safety and systemic usage of IL-4/13 monoclonal antibody treatment in BP.KEY MESSAGESBP is an autoimmune skin disease with Th2-mediated autoimmune response involvement.As typical Th2 cytokines, IL-4 and IL-13 may contribute to the pathogenesis of BP in multiple ways, such as promoting Th2 cell polarization, driving the immunoglobulin class switching, recruiting eosinophils and basophils, and inducing pruritus.As a promising therapeutic approach for BP, IL-4/13 antagonists have shown satisfactory outcomes in preliminary clinical studies.

Risk factors predisposing relapse of bullous pemphigoid at initial diagnosis: A retrospective cohort study of 205 patients.

BACKGROUND: Previous studies have revealed the factors associated with the relapse of bullous pemphigoid (BP). This study aims to assess the characteristics of BP patients at the time of initial diagnosis and a potential association with subsequent relapse occurrences. METHODS: A retrospective cohort study was conducted on 205 BP patients from January 2009 to May 2022 at the Peking Union Medical College Hospital in Beijing, China. The median follow-up duration was 2.7 years. We conducted univariate and multivariate analyses on various clinical indicators (e.g., lesional involvements and medical history) and laboratory test results. RESULTS: Among the 205 patients, 118 (57.6 %) relapsed during the follow-up period. Univariate analysis revealed several factors associated with relapse, which were greater age [Hazard Ratio (HR)1.018, 95 % confidence interval (CI) 1.004-1.032] (p = 0.010), a past medical history of thyroid diseases [HR 3.674, 95 % CI 1.472-9.167] (p = 0.005), hematological disease complications [HR 4.123, 95 % CI 1.301-13.061] (p = 0.016), negative C3 deposition in direct immunofluorescence [HR 0.574, 95 % CI 0.374-0.883] (p = 0.011) and prealbumin level less than 200 mg/L[HR 0.580, 95 % CI 0.351-0.957] (p = 0.033). Multivariate analysis demonstrated that patients with negative C3 deposition in direct immunofluorescence [HR 0.524, 95 % CI 0.296-0.927] (p = 0.026) and prealbumin levels below 200 mg/L [HR 0.541, 95 % CI 0.301-0.974] (p = 0.041) were associated with further relapses of BP. CONCLUSIONS: Negative C3 deposition in direct immunofluorescence and a prealbumin level below 200 mg/L at initial diagnosis served as predictive markers for future relapses of BP. Systemic evaluation of BP patients at initial diagnosis could be essential in helping prevent recurrences and achieve more effective disease management.

The health-related quality of life for hemiarthroplasty and total hip arthroplasty in the elderly: A meta-analysis.

Purpose: What constitutes the optimal surgical plan for femoral neck fractures (FNFs) in elderly patients is controversial. The European quality of life 5-Dimension Questionnaire (EU-5Q) is an international scale used to measure the health-related quality of life (HRQoL) after surgery. We aim to verify the hip arthroplasty effect in elderly patients by analyzing HRQoL scores in the EU-5Q scale. Methods: We searched the EBSCO, Embase, PubMed, Ovid, Cochrane Library, and Web of Science databases using strict searching from established to 30 November 2022; used the Cochrane Library's Risk of Bias Assessment Tool and the Newcastle-Ottawa Scale to evaluate the literature; and used RevMan5.4.1 software to perform a meta-analysis. All the included studies used the EU-5Q scale to validate the overall outcomes for elderly hip arthroplasty. Results: The final included literature is composed of four RCTs, two cohort studies, three case-control trials, and three cross-sectional surveys. This study compared HRQoL scores measured by the EU-5Q scale, including 328 elderly patients with total hip arthroplasty (THA) and 323 elderly patients with hemiarthroplasty, which is statistically significant (OR = 0.05; 95% CI, 0.02~0.08; P = 0.002). The subgroups were as follows: unipolar vs. bipolar and cemented vs. uncemented hemiarthroplasty (OR = 0.06; 95% CI, 0.03~0.08; P < 0.001), follow-up time and age arthroplasty (OR = 0.16; 95% CI, 0.11~0.22; P < 0.001), molecular exercise and enhanced recovery after surgery (ERAS) (OR = 0.02; 95% CI,-0.03~0.07; P = 0.38), and analysis of hemiarthroplasty with cognitive dysfunction vs. the normal group (OR = 0.17; 95% CI, 0.08~0.26; P < 0.001). The outcome analysis was consistent with the included studies, and HRQoL of the EU-5Q scale is sensitive to surgical outcomes between THA and hemiarthroplasty. Conclusion: Surgeons still need to further evaluate and verify whether the hip arthroplasty surgical program or effect in elderly patients is optimal. Hemiarthroplasty operations in elderly patients have pointed toward a new direction for clinical treatment, and HRQoL scores measured by the EU-5Q can sensitively reflect the rehabilitation status after hip arthroplasty surgery. Moreover, the extensive correlation between surgical outcomes and perioperative neurocognitive function should be further investigated.

Conformal phosphor coating using capillary microchannel for controlling color deviation of phosphor-converted white light-emitting diodes.

We demonstrated a conformal phosphor coating method for phosphor-converted white light-emitting diodes (LEDs) using capillary microchannel formed by a fixture. The mixture of the phosphor particles and the silicone spontaneously flows in capillary microchannel and was pinned at the edge of the fixture due to the surface tension effect. The present coating method was applied to different packaging types with both the conventional chip and the vertical injection chip. Experimental results show this method can efficiently improve the angular color uniformity (ACU). Compared with those samples packaged by conventional dispensing coating, angular color correlated temperature (CCT) deviation of the test samples by the present method can reduce from 1500K to 200K for the average CCT 5200K from -90° to +90 view angles, and reduce from 5000K to 1000K for the average CCT 9150K. Additionally, this method can prevent the packaging non-consistency that the average CCT varies from package to package due to the deviation of phosphor-silicone mixture volume. In the experiments, even when the phosphor-silicone mixture volume varies from 0.3 µl to 0.5 µl, the deviation of the average CCT is less than 80K.

Recent progress on RE2O3-Mo/W emission materials.

RE2O3-Mo/W cathodes were prepared by powder metallurgy method. La2O3-Y2O3-Mo cermet cathodes prepared by traditional sintering method and spark plasma sintering (SPS) exhibit different secondary emission properties. The La2O3-Y2O3-Mo cermet cathode prepared by SPS method has smaller grain size and exhibits better secondary emission performance. Monte carlo calculation results indicate that the secondary electron emission way of the cathode correlates with the grain size. Decreasing the grain size can decrease the positive charging effect of RE2O3 and thus is favorable for the escaping of secondary electrons to vacuum. The Scandia doped tungsten matrix dispenser cathode with a sub-micrometer microstructure of matrix with uniformly distributed nanometer-particles of Scandia has good thermionic emission property. Over 100 A/cm2 full space charge limited current density can be obtained at 950Cb. The cathode surface is covered by a Ba-Sc-O active surface layer with nano-particles distributing mainly on growth steps of W grains, leads to the conspicuous emission property of the cathode.

Prognostic analysis of pT1-T2aN0M0 cervical adenocarcinoma based on random survival forest analysis and the generation of a predictive nomogram.

Background: The efficacy of adjuvant radiotherapy for postoperative patients with early-stage cervical adenocarcinoma who are lymph node-negative is still inconclusive. Establishing a nomogram to predict the prognosis of such patients could facilitate clinical decision-making. Methods: We recruited 4636 eligible patients with pT1-T2aN0M0 cervical adenocarcinoma between 2004 and 2016 from the Surveillance, Epidemiology and End Results (SEER) database. Random survival forest (RSF) and conditional survival forest (CSF) model was used to assess the prognostic importance of each clinical characteristic variable. We identified independent prognostic factors associated with overall survival (OS) by univariate and multivariate Cox regression risk methods and then constructed a nomogram. We stratified patients based on nomogram risk scores and evaluated the survival benefit of different adjuvant therapies. To reduce confounding bias, we also used propensity score matching (PSM) to match the cohorts before performing survival analyses. Results: The RSF and CSF model identified several important variables that are associated with prognosis, including grade, age, radiotherapy and tumor size. Patients were randomly divided into training and validation groups at a ratio of 7:3. Multivariate cox analysis revealed that age, grade, tumor size, race, radiotherapy and histology were independent prognostic factors for overall survival. Using these variables, we then constructed a predictive nomogram. The C-index value for evaluating the prognostic nomogram fluctuated between 0.75 and 0.91. Patients were divided into three subgroups based on risk scores, and Kaplan-Meier (K-M) survival analysis revealed that in the low-risk group, postoperative chemotherapy alone was associated with a significantly worse OS than surgery alone. Following PSM, survival analysis showed that compared with surgery alone, radiotherapy was associated with a worse OS in the training group although there was no significant difference in the validation group. Conclusions: For patients with pT1-T2aN0M0 cervical adenocarcinoma, adjuvant treatments such as postoperative radiotherapy or chemotherapy, compared with surgery alone, are of no benefit with regards to patient survival. Our prognostic nomogram exhibits high accuracy for predicting the survival of patients with early-stage postoperative cervical adenocarcinoma.