RESUMEN
Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.
Asunto(s)
Antígenos HLA , Trasplante de Células Madre Hematopoyéticas , Isoanticuerpos , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Donantes de Tejidos , Rechazo de Injerto/inmunología , Intercambio Plasmático/métodos , Adolescente , Trasplante Haploidéntico/métodos , Adulto Joven , Biomarcadores/sangre , Desensibilización Inmunológica/métodosRESUMEN
The code of industrial management software typically features few system API calls and a high number of customized variables and structures. This makes the similarity of such codes difficult to compute using text features or traditional neural network methods. In this paper, we propose an FSPS-GNN model, which is based on graph neural networks (GNNs), to address this problem. The model categorizes code features into two types, outer graph and inner graph, and conducts training and prediction with four stages-feature embedding, feature enhancement, feature fusion, and similarity prediction. Moreover, differently structured GNNs were used in the embedding and enhancement stages, respectively, to increase the interaction of code features. Experiments with code from three open-source projects demonstrate that the model achieves an average precision of 87.57% and an F0.5 Score of 89.12%. Compared to existing similarity-computation models based on GNNs, this model exhibits a Mean Squared Error (MSE) that is approximately 0.0041 to 0.0266 lower and an F0.5 Score that is 3.3259% to 6.4392% higher. It broadens the application scope of GNNs and offers additional insights for the study of code-similarity issues.
RESUMEN
Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.
Asunto(s)
Antibacterianos , Ceftizoxima , Hemoglobinas , Insuficiencia Multiorgánica , Neoplasias del Recto , Humanos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/inmunología , Neoplasias del Recto/cirugía , Hemoglobinas/metabolismo , Antibacterianos/efectos adversos , Masculino , Ceftizoxima/efectos adversos , Insuficiencia Multiorgánica/etiología , Persona de Mediana Edad , Anemia Hemolítica/inducido químicamente , Anemia Hemolítica/inmunología , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiología , Anemia Hemolítica Autoinmune/inducido químicamente , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/diagnóstico , China , Pueblos del Este de AsiaRESUMEN
BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.
Asunto(s)
Trastornos de Ansiedad , Trastorno Depresivo Mayor , Fragilidad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neuroticismo , Humanos , Fragilidad/genética , Fragilidad/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/epidemiología , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Masculino , Anciano , Femenino , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido SimpleRESUMEN
HLA-B*46:01:42 differs from HLA-B*46:01:01:01 by one nucleotide in exon 5.
Asunto(s)
Genes MHC Clase I , Nucleótidos , Humanos , Alelos , Antígenos HLA-B/genética , China , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: The dysfunction of the ABO glycosyltransferase (GT) enzyme, which is caused by mutations in the ABO gene, can lead to weak ABO phenotypes. In this study, we have discovered a novel weak ABO subgroup allele and investigated the underlying mechanism to causing its Aweak phenotype. MATERIALS AND METHODS: The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of ABO gene. The role of the novel single nucleotide polymorphism (SNP) was evaluated by 3D model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. RESULTS: The results of serological showed the subject was Aweak phenotype. A novel SNP c.424A > G (p. M142V) based on ABO*A1.02 was identified, and the genotype of the subject was AW-var/O.01 according to the gene analysis. In silico analysis showed that the SNP c.424A > G on the A allele may change the local conformation by damaging the hydrogen bonds and reduce the stability of GT. In vitro expression study showed that SNP p.M142V impaired H to A antigen conversion, although it did not affect the generation of A glycosyltransferase (GTA). CONCLUSIONS: One novel AW allele was identified and the SNP c.424A > G (p.M142V) can cause the Aweak phenotype through damaging the hydrogen bonds and reducing stability of the GTA.
RESUMEN
PURPOSE: To identify long-term predictors of distant metastases (DM) and the overall survival (OS) of follicular thyroid cancer (FTC) patients who underwent radioactive iodine (RAI) therapy. And to expand the knowledge about the clinical course and experience of RAI treatment for FTC. MATERIALS: A total of 117 FTC patients who underwent RAI therapy at our institution from 2005 to 2020 were retrospectively studied. Patient characteristics, serum stimulating thyroglobulin (sTg) and thyroglobulin antibody levels, treatment process and follow-up data were collected until 26 April 2022. RESULTS: A total of 16 patients (13.7%) were lost to follow-up. A total of 23 (19.7%) patients with DM died and all FTC without DM were still alive. DM was seen in 58.4% (59/101) of patients. The most common location for metastatic lesions was the lung. Then was bone. The mean survival time of FTC with RAI was 156 months [95% confidence interval (CI): 142-171]. Five-year and 10-year cumulative survival rates of them were 88.8% and 67.4%, respectively. As for patients with DM were 80.4% and 41.3%, respectively. Age at diagnosis [odds ratio (OR)â =â 1.080, P â =â 0.009], RAI therapy sessions (ORâ =â 2.959, P â =â 0.001) and sTg level (ORâ =â 1.006, P â =â 0.002) were predictive of DM occurrence in FTC with RAI. In the group of FTC with DM, survival analysis showed that males were more likely to have a lower OS than females ( P â =â 0.039). CONCLUSION: Age, number of RAI therapy sessions, and sTg level were predictive of the occurrence of DM in FTC patients with RAI. Sex would influence the OS of FTC patients with DM.
Asunto(s)
Adenocarcinoma Folicular , Tiroglobulina , Neoplasias de la Tiroides , Masculino , Femenino , Humanos , Estudios de Seguimiento , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo/uso terapéutico , Estudios Retrospectivos , Tiroidectomía , ChinaRESUMEN
H2 O2 is a widely used eco-friendly oxidant and a potential energy carrier. Photocatalytic H2 O2 production from water and O2 is an ideal approach with the potential to address the current energy crisis and environmental issues. Three zig-zag two-dimensional coordination polymers (2D CPs), named CuX-dptz, were synthesized by a rapid and facile method at room temperature, showing preeminent H2 O2 photoproduction performance under pure water and open air without any additives. CuBr-dptz exhibits a H2 O2 production rate high up to 1874â µmol g-1 h-1 , exceeding most reported photocatalysts under this condition, even comparable to those supported by sacrificial agents and O2 . The coordination environment of Cu can be modulated by halogen atoms (X=Cl, Br, I), which in turn affects the electron transfer process and finally determines the reaction activity. This is the first time that 2D CPs have been used for photocatalytic H2 O2 production in such challenging conditions, which provides a new pathway for the development of portable in situ H2 O2 photosynthesis devices.
RESUMEN
Composites are widely used in high performance structures such as aerospace structures due to their excellent properties. The analysis of failure evolution of composite perforated structures by finite element simulation is of great significance for practical work as engineering composite structures often contain notches and voids. In this paper, the numerical simulation of failure evolution and failure modes of carbon fiber reinforced resin composite laminates with large openings was carried out. A UMAT subroutine was written based on the 3D Hashin-Ye failure criterion and progressive damage model theory. The characteristic length and viscosity coefficient were introduced into the model to reduce mesh dependency and improve computational convergence. The nonlinear shear constitutive relationship defined by the Ramberg-Osgood equation was introduced into the continuous damage degradation model. The effect of nonlinear shear on the failure evolution of laminates with different stacking sequence was studied.
RESUMEN
Three-dimensional face recognition is an important part of the field of computer vision. Point clouds are widely used in the field of 3D vision due to the simple mathematical expression. However, the disorder of the points makes it difficult for them to have ordered indexes in convolutional neural networks. In addition, the point clouds lack detailed textures, which makes the facial features easily affected by expression or head pose changes. To solve the above problems, this paper constructs a new face recognition network, which mainly consists of two parts. The first part is a novel operator based on a local feature descriptor to realize the fine-grained features extraction and the permutation invariance of point clouds. The second part is a feature enhancement mechanism to enhance the discrimination of facial features. In order to verify the performance of our method, we conducted experiments on three public datasets: CASIA-3D, Bosphorus, and Lock3Dface. The results show that the accuracy of our method is improved by 0.7%, 0.4%, and 0.8% compared with the latest methods on these three datasets, respectively.
RESUMEN
Aqueous batteries are promising alternatives to non-aqueous lithium-ion batteries due to their safety, environmental impact, and cost-effectiveness. However, their energy density is limited by the narrow electrochemical stability window (ESW) of water. The "Water-in-salts" (WIS) strategy is an effective method to broaden the ESW by reducing the "free water" in the electrolyte, but the drawbacks (high cost, high viscosity, poor low-temperature performance, etc.) also compromise these inherent superiorities. In this review, electrolyte and interphase engineering of aqueous batteries to overcome the drawbacks of the WIS strategy are summarized, including the developments of electrolytes, electrode-electrolyte interphases, and electrodes. First, the main challenges of aqueous batteries and the problems of the WIS strategy are comprehensively introduced. Second, the electrochemical functions of various electrolyte components (e.g., additives and solvents) are summarized and compared. Gel electrolytes are also investigated as a special form of electrolyte. Third, the formation and modification of the electrolyte-induced interphase on the electrode are discussed. Specifically, the modification and contribution of electrode materials toward improving the WIS strategy are also introduced. Finally, the challenges of aqueous batteries and the prospects of electrolyte and interphase engineering beyond the WIS strategy are outlined for the practical applications of aqueous batteries.
RESUMEN
BACKGROUND AND OBJECTIVES: ABO antigens are produced from H antigen by the activity of glycosyltransferase enzyme encoded by the ABO gene. Variants in the ABO gene can produce a weak ABO phenotype. In this study, we identify a novel ABO*BW allele and investigate the underlying mechanism leading to the Bweak phenotype. MATERIALS AND METHODS: The ABO phenotype and genotype of the sample were determined using serological and direct DNA sequencing methods. We assessed the impact of the novel variant by three-dimensional modelling to predict protein stability changes (ΔΔG), and carried out an in vitro expression assay. The total glycosyltransferase transfer capacity in the supernatant of transfected cells was also examined. RESULTS: Serological analysis confirmed the Bweak phenotype in the subject, and gene sequencing identified a novel variant c.761C>T (p.A254V) on the ABO*B.01 allele, resulting in a BW-var/O.01.02 genotype. In silico analysis suggested that the p.A254V variant on the B allele may reduce the stability of glycosyltransferase B (GTB), as indicated by the ΔΔG values. In vitro expression studies showed that the variant p.A254V impaired H to B antigen conversion, although it did not affect the expression of GTB. CONCLUSION: We identified a novel BW allele and demonstrated that the variant c.761C>T (p.A254V) can cause the Bweak phenotype by reducing the stability of GTB.
RESUMEN
HLA-B*51:381 differs from HLA-B*51:01:01:01 by one nucleotide in exon 5.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia/genética , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
Background: Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear. Methods: The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and the genome-wide statistical significance threshold (5 × 10-8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran's Q test, and leave-one-out test, were carried out to assess the robustness of our findings. Results: Our study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy. Conclusion: This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.
RESUMEN
Suitable electrocatalysts for industrial water splitting can veritably promote practical hydrogen applications. Rational surface design is exceptionally significant for electrocatalysts to bridge the gap between fundamental science and industrial expectation in water splitting. Here, Pt-quantum-dot-modified sulfur-doped NiFe layered double hydroxides (Pt@S-NiFe LDHs) are designed with eximious catalytic activity toward hydrogen evolution reaction (HER) under industrial condition. Benefiting from enhanced binding energy, mass transfer, and hydrogen release, Pt@S-NiFe LDHs exhibit outstanding activity in HER at high current densities. Notably, it obtains an impressively low overpotential of 71 mV and long-term stability of 200 h at 100 mA cm-2 , exceeding commercial 40% Pt/C and most reported Pt-based electrocatalysts. Its mass activity is 2.7 times higher than that of 40% Pt/C with an overpotential of 100 mV. Furthermore, at industrial temperature (65 °C), the electrolyzer based on Pt@S-NiFe LDH needs just 1.62 V to reach the current density of 100 mA cm-2 , superior to that of the commercial one of 40% Pt/C//IrO2 . This work provides rational ideas to develop electrocatalysts with exceptional performance for industrial high-temperature water splitting at high current densities.
RESUMEN
BACKGROUND: Platelets are anucleated blood cells and contain various RNA species. We investigated the changes in the whole transcriptome expression profile of platelet concentrates (PC) during storage to explore biological functions and biomarkers in platelet storage damage. MATERIALS AND METHODS: Platelets were collected by apheresis from eight healthy blood donors and stored from day 0 to day 4. Platelet phenotyping and function analysis were used to detect platelet activity during storage. RNA-sequencing was used to detect changes in expression of mRNA, lncRNA and circRNA in the PC during storage. Gene ontology and KEGG analyses were applied to predict the functional distribution of differential expression of mRNA. Gene set enrichment analysis was used to analyze the differential levels of gene pathways. Finally, polymerase chain reaction (PCR) analysis was performed to verify the expression of three mRNA (POLE2, DCUN1D4, DAD1). RESULTS: In total, 10,767 mRNA, 2,923 lncRNA and 68,550 circRNA were detected in the PC by RNA-sequencing. The expression levels of 222 mRNA changed significantly from day 0 to day 4 of storage: 58 increased continuously and 145 decreased continuously. Differentially expressed mRNA may be involved in physiological processes such as platelet activation, platelet aggregation, endocytosis, and apoptosis. Expression levels of 1,413 lncRNA were obvious. The levels of 42 species increased and the levels of 28 species decreased. The expression levels of 198 species of circRNA changed significantly, with those of 13 species changing continuously. The differential levels of expression of DAD1, DCUN1D4 and POLE1 mRNA, shown by RNA sequencing, were validated by PCR assay. DISCUSSION: Changes in mRNA, lncRNA and circRNA during platelet storage may be closely related to platelet apoptosis and physiological functions in the platelet storage lesion. The expression levels of DAD1, DCUN1D4 and POLE1 could be biomarkers to monitor platelet status in PC bags.