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OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.
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Diabetes Mellitus , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Factores de Riesgo , Diabetes Mellitus/etiología , Receptores de TrasplantesRESUMEN
BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T. METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized. RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites. CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.
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Microbioma Gastrointestinal , Trasplante de Riñón , Humanos , Metaboloma , Aminoácidos , RiñónRESUMEN
Hepatocellular carcinoma (HCC) is a rapidly growing tumor characterized by a high potential for vascular invasion and metastasis. The purpose of our study is to explore the regulation mechanism of long noncoding RNA (lncRNA) LINC01419 on cell-cycle distribution and metastasis in hepatocellular carcinoma (HCC) by regulating zinc finger of the cerebellum (ZIC1) through PI3K/Akt signaling pathway. Bioinformatics analysis and dual-luciferase reporter assay were used to analyze LINC01419 and related genes in HCC, and their expression in HCC tissues and adjacent normal tissues were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Then, HCC cell lines were subjected to the construction of LINC01419/ZIC1 overexpression/knockdown cells utilizing lentiviral vectors. RIP and ChIP assays were applied to identify the LINC01419-binding protein. BSP and MSP assays were used to determine gene methylation. According to the results, LINC01419 was highly expressed in HCC tissues and cells, while ZIC1 was poorly expressed. LINC01419 targeted and downregulated ZIC1 expression. Furthermore, LINC01419 increased the methylation of ZIC1 promoter and repressed ZIC1 expression. PI3K/Akt signaling pathway was activated by LINC01419 overexpression and ZIC1 knockdown, under which conditions, the HCC cell self-renewal and proliferation were promoted while cell apoptosis was attenuated, accompanied by accelerated formation and metastasis of xenografted tumors in mice. In conclusion, LINC01419 enhances the methylation of ZIC1 promoter, inhibits ZIC1 expression, and activates the PI3K/Akt signaling pathway, thereby enhancing the malignant phenotypes of HCC cells in vitro as well as tumor formation and metastasis in vivo.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , ARN Largo no Codificante/metabolismo , Factores de Transcripción/metabolismo , Adulto , Línea Celular Tumoral , Metilación de ADN , Progresión de la Enfermedad , Epigénesis Genética , Femenino , Silenciador del Gen , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción/genética , Adulto JovenRESUMEN
Regulatory B cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known about their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naïve B cells, stimulated by TLR ligand agonists, converted into B cells with regulatory properties (Bregs-TLR) that prevented allograft rejection. Here, we examine the granular phenotype and regulatory properties of Breg-TLR cells suppressing B cells. Cocultures of Bregs-TLR with LPS-activated B cells showed a dose-dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs-TLR induced a decline in antibody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell-deficient mice replenished with transgenic BCR (OB1) and TCR (OT-II) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B cells, mediated through help from CD4+ OT-II cells, was suppressed by OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs-TLR suppression is associated with a block in targeted B cell differentiation controlled by PRDM1 (Blimp1). This work uncovered the regulatory properties of a new brand of Breg cells and provided mechanistic insights into potential applications of Breg therapy in transplantation.
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Linfocitos B Reguladores , Traslado Adoptivo , Animales , Técnicas de Cocultivo , Activación de Linfocitos , RatonesRESUMEN
OBJECTIVE: To investigate the association between graft-derived cell-free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function. METHODS: A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14-20, and 30-45 after transplantation. The fractional abundance of graft-derived cell-free DNA was determined using droplet digital polymerase chain reaction. RESULTS: For most recipients, graft-derived cell-free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft-derived cell-free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft-derived cell-free DNA fraction values (P = 0.02). Moreover, we also found that graft-derived cell-free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan-Meier analysis showed that recipients who had a graft-derived cell-free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values. CONCLUSIONS: Our findings suggest that graft-derived cell-free DNA might be used as a novel biomarker to predict delayed graft function and renal function.
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Ácidos Nucleicos Libres de Células , Trasplante de Riñón , Aloinjertos , Biomarcadores , Tasa de Filtración Glomerular , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Trasplante HomólogoRESUMEN
During the 2019 novel coronavirus (SARS-CoV-2) outbreak in China (from January 24 to March 11, 2020), our center performed 16 organ transplants (10 kidney, 4 liver, and 2 lung transplants) harvested from deceased donors. Regarding the strategies to prevent infections of SARS-CoV-2, we implemented specific measures for the donor and recipient management, as well as prevention of hospital-acquired infections. All 16 organ recipients had a favorable outcome without SARS-CoV-2 infection. Our approaches aiming to interrupt the spread of SARS-CoV-2 within the transplantation wards were successful, and allowed us to maintain the transplantation program for deceased liver, kidney, and lung organ recipients.
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Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Trasplante de Órganos/tendencias , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Donantes de Tejidos , Betacoronavirus , COVID-19 , Prueba de COVID-19 , China/epidemiología , Técnicas de Laboratorio Clínico , Control de Enfermedades Transmisibles , Infecciones por Coronavirus/diagnóstico , Infección Hospitalaria/prevención & control , Humanos , Unidades de Cuidados Intensivos , Trasplante de Riñón , Trasplante de Hígado , Trasplante de Pulmón , Trasplante de Órganos/métodos , SARS-CoV-2 , Resultado del TratamientoRESUMEN
BACKGROUND: Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Whether the prophylactic administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) peri-ERCP is effective in preventing post-ERCP pancreatitis (PEP) remains controversial. The aim of this study was to assess the effect of rectal NSAIDs on PEP. METHODS: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE, and Web of Science) was performed to identify eligible randomized controlled trials (RCTs). The Jadad score for assessing risk of bias was used to evaluate the quality of included studies. The primary endpoint of the study was efficacy for PEP prevention. Sub-analyses were performed to determine the risk reduction for different NSAID types, for general vs. high-risk patients, by timing of administration and for moderate to severe PEP. RESULTS: Twelve RCTs, including a total of 3989 patients, were identified and included in the analysis. The risk of PEP was lower in the NSAIDs group than in the placebo group (RR 0.52; 95% CI 0.43-0.64; P < 0.01). The risk of moderate to severe PEP was also lower in the NSAIDs group. (RR 0.44; 95% CI 0.28-0.69; P < 0.01). There was no difference in efficacy between rectal indomethacin and diclofenac, nor between pre-ERCP and post-ERCP administration timing of rectal NSAIDs. CONCLUSIONS: A single rectal dose of NSAIDs is effective in preventing PEP both in high-risk and in unselected patients, regardless of timing of administration (pre- or post-ERCP) and NSAID type (indomethacin or diclofenac).
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Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/etiología , Pancreatitis/prevención & control , Complicaciones Posoperatorias/prevención & control , Administración Rectal , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Implantación de Prótesis Vascular/métodos , Síndrome de Budd-Chiari/cirugía , Equinococosis Hepática/cirugía , Venas Hepáticas/cirugía , Stents , Adolescente , Adulto , Síndrome de Budd-Chiari/complicaciones , Síndrome de Budd-Chiari/diagnóstico , Equinococosis Hepática/complicaciones , Equinococosis Hepática/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Despite accumulated experience and advancing techniques for laparoscopic hepatectomy, bleeding remains the major concern during parenchymal transection. The vascular inflow control technique is still important to decrease intraoperative blood loss. The objective of this study was to compare intermittent Pringle with continuous hemihepatic vascular inflow occlusion using extra-glissonian approach in laparoscopic liver resection. METHODS: Between January 2011 and January 2015, a total of 79 consecutive patients with tumors locating either in the right or in the left hemiliver were included into this retrospective study (45 in the Pringle group vs. 34 in the half-Pringle group). Preoperative clinical characteristics, intraoperative details, postoperative complications and outcomes of patients were compared. RESULTS: The two groups were well matched according to clinical characteristics, tumor features, types of liver resection and histopathology (P > 0.05). The mean operative time (247.5 ± 61.3 vs. 221.4 ± 48.7 min, P = 0.0446), ischemic duration (62.8 ± 28.3 vs. 44.1 ± 20.5 min, P = 0.0017) and overall declamping time (21.2 ± 8.2 vs. 0.9 ± 1.9 min, P < 0.05) were significantly longer in the Pringle group than in the half-Pringle group. The mean amount of intraoperative blood loss (568.2 ± 325.1 vs. 420.7 ± 307.2 mL, P = 0.0444) and transfusion (266.1 ± 123.4 vs. 203.2 ± 144.6 mL, P = 0.0406) were significantly greater in the Pringle group. The overall operative morbidity rate was significantly higher in the Pringle group (40 vs. 17.6%, P = 0.0324). The Pringle group was associated with significantly higher alanine aminotransferase and aspartate transaminase levels on postoperative day (POD) 7 and lower albumin levels on PODs 1 and 3 (P < 0.05). The C-reactive protein levels were significantly higher in the Pringle group than in the half-Pringle group on POD 1 (37.5 ± 21.4 vs. 28.2 ± 19.0 mg/L, P = 0.0484), POD 3 (114.0 ± 53.4 vs. 90.6 ± 47.9 mg/L, P = 0.0474) and POD 7 (54.9 ± 29.8 vs. 40.1 ± 26.4 mg/L, P = 0.0245). CONCLUSION: Continuous hemihepatic vascular inflow occlusion using extra-glissonian approach offers the advantages of less operative time and blood loss, less injury and better recovery in laparoscopic liver resection.
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Pérdida de Sangre Quirúrgica/prevención & control , Hepatectomía/métodos , Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Transfusión Sanguínea/estadística & datos numéricos , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
Over the past few decades, there has been a remarkable advancement in the field of transplantation. But the shortage of donors is still an urgent problem that requires immediate attention. As with xenotransplantation, bioengineered organs are promising solutions to the current shortage situation. And decellularization is a unique technology in organ-bioengineering. However, at present, there is no unified decellularization method for different tissues, and there is no gold-standard for evaluating decellularization efficiency. Meanwhile, recellularization, re-endothelialization and modification are needed to form transplantable organs. With this mind, we can start with decellularization and re-endothelialization or modification of small blood vessels, which would serve to address the shortage of small-diameter vessels while simultaneously gathering the requisite data and inspiration for further recellularization of the whole organ-scale vascular network. In this review, we collect the related experiments of decellularization and post-decellularization approaches of small vessels in recent years. Subsequently, we summarize the experience in relation to the decellularization and post-decellularization combinations, and put forward obstacle we face and possible solutions.
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BACKGROUND: Generative Artificial Intelligence (AI) technology, for instance Chat Generative Pre-trained Transformer (ChatGPT), is continuously evolving, and its userbase is growing. These technologies are now being experimented by the businesses to leverage their potential and minimise their risks in business operations. The continuous adoption of the emerging Generative AI technologies will help startups gain more and more experience with adoptions, helping them to leverage continuously evolving technological innovation landscape. However, there is a dearth of prior research on ChatGPT adoption in the startup context, especially from Entrepreneur perspective, highlights the urgent need for a thorough investigation to identify the variables influencing this technological adoption. The primary objective of this study is to ascertain the factors that impact the uptake of ChatGPT technology by startups, anticipate their influence on the triumph of companies, and offer pragmatic suggestions for various stakeholders, including entrepreneurs, and policymakers. METHOD AND ANALYSIS: This study attempts to explore the variables impacting startups' adoption of ChatGPT technology, with an emphasis on comprehending entrepreneurs' attitudes and perspectives. To identify and then empirically validate the Generative AI technology adoption framework, the study uses a two-stage methodology that includes experience-based research, and survey research. The research method design is descriptive and Correlational design. Stage one of the research study is descriptive and involves adding practical insights, and real-world context to the model by drawing from the professional consulting experiences of the researchers with the SMEs. The outcome of this stage is the adoption model (also called as research framework), building Upon Technology Adoption Model (TAM), that highlight the technology adoption factors (also called as latent variables) connected with subset of each other and finally to the technology adoption factor (or otherwise). Further, the latent variables and their relationships with other latent variables as graphically highlighted by the adoption model will be translated into the structured questionnaire. Stage two involves survey based research. In this stage, structured questionnaire is tested with small group of entrepreneurs (who has provided informed consent) and finally to be distributed among startup founders to further validate the relationships between these factors and the level of influence individual factors have on overall technology adoption. Partial Least Squares Structural Equation Modeling (PLS-SEM) will be used to analyze the gathered data. This multifaceted approach allows for a comprehensive analysis of the adoption process, with an emphasis on understanding, describing, and correlating the key elements at play. DISCUSSION: This is the first study to investigate the factors that impact the adoption of Generative AI, for instance ChatGPT technology by startups from the Entrepreneurs perspectives. The study's findings will give Entrepreneurs, Policymakers, technology providers, researchers, and Institutions offering support for entrepreneurs like Academia, Incubators and Accelerators, University libraries, public libraries, chambers of commerce, and foreign embassies important new information that will help them better understand the factors that encourage and hinder ChatGPT adoption. This will allow them to make well-informed strategic decisions about how to apply and use this technology in startup settings thereby improving their services for businesses.
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Inteligencia Artificial , Tecnología , Humanos , Transporte Biológico , Colina O-Acetiltransferasa , ComercioRESUMEN
RATIONALE AND OBJECTIVES: To evaluate the predictive value of tumor and peritumor radiomics in the fatty acid binding protein 4 (FABP4) expression levels and overall survival in patients with hepatocellular carcinoma. MATERIALS AND METHODS: The genomic data of HCC patients were obtained from The Cancer Genome Atlas. The Dual-area CT images of corresponding patients were downloaded from The Cancer Imaging Archive, for radiomics feature extraction, model construction and prognosis analysis. Simultaneously, using patients from Sichuan Provincial People's Hospital, the prognostic value of the radiomics model in HCC patients was validated. RESULTS: In the TCIA database, the area under the curve (AUC) values of the volumes of interest (VOI)whole model in the training set and internal validation set were 0.812 and 0.754, respectively, and the AUC value of VOIwhole+periphery in the training set and internal validation set were 0.866 and 0.779, respectively. In the VOIwhole and the VOIwhole+periphery model of the independent cohort, there were significant differences in OS between the high and low rad-score groups (P = 0.009, P = 0.021, respectively). Significant positive correlations can be observed between FABP4 expression and correlations with rad-score of VOIwhole model (r = 0.691) and VOIwhole+periphery model (r = 0.732) in the independent cohort. CONCLUSION: Radiomics models of tumor and peritumor Dual-area CT images could predict stably the expression levels of FABP4 and may be helping in personalized treatment strategies.
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Carcinoma Hepatocelular , Proteínas de Unión a Ácidos Grasos , Neoplasias Hepáticas , Tomografía Computarizada por Rayos X , Humanos , Proteínas de Unión a Ácidos Grasos/metabolismo , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Valor Predictivo de las Pruebas , Anciano , Adulto , Estudios Retrospectivos , RadiómicaRESUMEN
Introduction: Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs. Methods: This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results. Results: The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], P=0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, P=0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, P=0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, P=0.018) was a protective factor against death in severe COVID-19. Conclusions: Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.
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COVID-19 , Trasplante de Riñón , Humanos , Adulto , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Prueba de COVID-19 , COVID-19/etiología , Factores de Riesgo , AloinjertosRESUMEN
Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.
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Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Bevacizumab , Microbioma Gastrointestinal , Inhibidores de Puntos de Control Inmunológico , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Bevacizumab/uso terapéutico , Bevacizumab/farmacología , Masculino , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Persona de Mediana Edad , Anciano , Mesotelioma Maligno/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Mesotelioma/inmunología , Mesotelioma/tratamiento farmacológico , Mesotelioma/microbiología , Mesotelioma/patología , Microambiente Tumoral/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiología , Resultado del TratamientoRESUMEN
Carbon dioxide (CO2) is a crucial greenhouse gas with substantial effects on climate change. Satellite-based remote sensing is a commonly used approach to detect CO2 with high precision but often suffers from extensive spatial gaps. Thus, the limited availability of data makes global carbon stocktaking challenging. In this paper, a global gap-free column-averaged dry-air mole fraction of CO2 (XCO2) dataset with a high spatial resolution of 0.1° from 2014 to 2020 is generated by the deep learning-based multisource data fusion, including satellite and reanalyzed XCO2 products, satellite vegetation index data, and meteorological data. Results indicate a high accuracy for 10-fold cross-validation (R2 = 0.959 and RMSE = 1.068 ppm) and ground-based validation (R2 = 0.964 and RMSE = 1.010 ppm). Our dataset has the advantages of high accuracy and fine spatial resolution compared with the XCO2 reanalysis data as well as that generated from other studies. Based on the dataset, our analysis reveals interesting findings regarding the spatiotemporal pattern of CO2 over the globe and the national-level growth rates of CO2. This gap-free and fine-scale dataset has the potential to provide support for understanding the global carbon cycle and making carbon reduction policy, and it can be freely accessed at https://doi.org/10.5281/zenodo.7721945.
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Dióxido de Carbono , Cambio Climático , Dióxido de Carbono/análisisRESUMEN
In this comprehensive meta-analysis, our objective was to evaluate the diagnostic utility of graft-derived cell-free DNA (GcfDNA) in kidney allograft rejection and explore associated factors. We conducted a thorough search of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to September 2022. Statistical analysis was executed utilizing Stata 15, Meta-DiSc 1.4, and Review Manager 5.4 software. The combined pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristics (SROC) curve from the synthesis of findings across ten studies were as follows: 0.75 (0.67-0.81), 0.78 (0.72-0.83), 3.36 (2.89-4.35), 0.32 (0.24-0.44), 8.77 (4.34-17.74), and 0.83 (0.80-0.86), respectively. Among the ten studies primarily focused on GcfDNA's diagnostic potential for antibody-mediated rejection (ABMR), the optimal cut-off threshold demonstrated substantial diagnostic efficacy, with pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the summary receiver operating characteristics curve values of 0.83 (0.74-0.89), 0.75 (0.70-0.80), 3.37 (2.64-4.30), 0.23 (0.15-0.36), 14.65 (7.94-27.03), and 0.85 (0.82-0.88), respectively. These results underscore the high diagnostic accuracy of GcfDNA in detecting rejection. Furthermore, the optimal cut-off threshold proves effective in diagnosing ABMR, while a 1% threshold remains a robust diagnostic criterion for rejection. Notably, for ABMR diagnosis, droplet digital PCR digital droplet polymerase chain reaction emerges as a superior method in terms of accuracy when compared to other techniques. Nonetheless, further research is warranted to substantiate these findings.
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Graft-derived cell-free DNA (GcfDNA) is a promising non-invasive biomarker for detecting allograft injury. In this study, we aimed to evaluate the efficacy of programmed monitoring of GcfDNA for identifying BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant recipients. We recruited 158 kidney transplant recipients between November 2020 and December 2021. Plasma GcfDNA was collected on the tenth day, first month, third month, and sixth month for programmed monitoring and one day before biopsy. ΔGcfDNA (cp/mL) was obtained by subtracting the baseline GcfDNA (cp/mL) from GcfDNA (cp/mL) of the latest programmed monitoring before biopsy. The receiver operating characteristic curve showed the diagnostic performance of GcfDNA (cp/mL) at biopsy time and an optimal area under the curve (AUC) of 0.68 in distinguishing pathologically proven BKPyVAN from pathologically unconfirmed BKPyVAN. In contrast, ΔGcfDNA (cp/mL) had a sensitivity and specificity of 80% and 84.6%, respectively, and an AUC of 0.83. When distinguishing clinically diagnosed BKPyVAN from clinical excluded BKPyVAN, the AUC of GcfDNA (cp/mL) was 0.59 at biopsy time, and ΔGcfDNA (cp/mL) had a sensitivity and specificity of 81.0% and 76.5%, respectively, and an AUC of 0.81. Plasma ΔGcfDNA (cp/mL) was not significantly different between TCMR [0.15 (0.08, 0.24) cp/mL] and pathologically proven BKPyVAN[0.34 (0.20, 0.49) cp/mL]. In conclusion, we recommend programmed monitoring of plasma GcfDNA levels after a kidney transplant. Based on our findings from the programmed monitoring, we have developed a novel algorithm that shows promising results in identifying and predicting BKPyVAN.
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Virus BK , Ácidos Nucleicos Libres de Células , Nefritis Intersticial , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Virus BK/genética , Infecciones Tumorales por Virus/diagnóstico , Rechazo de Injerto/diagnóstico , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/patología , Biomarcadores , AlgoritmosRESUMEN
Admittedly, the design requirements of compactness, low frequency, and broadband seem to constitute an impossible trinity, hindering the further development of elastic metamaterials (EMMs) in wave shielding engineering. To break through these constraints, we propose theoretical combinations of effective parameters for wave isolation based on the propagation properties of Lamb waves in the EMM layer. Accordingly, we design compact EMMs with a novel ultralow-frequency bandgap, and the role of auxeticity in the dissociation between the dipole mode and the toroidal dipole mode is clearly revealed. Finally, under the guidance of the improved gradient design, we integrate multiple bandgaps to assemble metamaterial barriers (MMBs) for broadband wave isolation. In particular, the original configuration is further optimized and its ultralow-frequency and broadband performance are proven by transmission tests. It is foreseeable that our work will provide a meaningful reference for the application of the new EMMs in disaster prevention and protection engineering.