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1.
BMC Infect Dis ; 24(1): 1141, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39394593

RESUMEN

PURPOSE: The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. METHODS: Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan-Meier product limit approach was employed. RESULTS: In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294-9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361-5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158-0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167-0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001). CONCLUSIONS: In conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Neoplasias Hematológicas , Inmunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/sangre , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/mortalidad , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/inmunología , Estudios Retrospectivos , SARS-CoV-2/inmunología , Inmunoglobulina G/sangre , Adulto , Anciano , Anticuerpos Antivirales/sangre , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunación
2.
Front Endocrinol (Lausanne) ; 15: 1441014, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39411311

RESUMEN

Objective: Intracytoplasmic sperm injection (ICSI) is commonly employed in preimplantation genetic testing (PGT) to minimize the risk of foreign sperm DNA contamination. Cryopreserved embryos from patients with recurrent miscarriage or repeated implantation failure, who have undergone conventional in vitro fertilization (IVF), can be thawed and biopsied for PGT. Therefore, we aimed to assess the accuracy and effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on frozen embryos using conventional IVF (c-IVF) insemination methods. Methods: From January 2021 to November 2023, our center conducted 107 thawed cryopreserved embryo biopsy cycles to screen for PGT-A. Among them, 58 cycles used c-IVF insemination, and 49 used ICSI insemination. Basic patient clinical information, laboratory data, PGT test results, and clinical outcome data were collected. To minimize the confounding effects of patient characteristics and embryo quality on PGT-A outcomes, clinical outcomes, and contamination assessment, these variables were included in the analysis. We then evaluated the blastocyst euploidy rate, clinical outcomes, and accuracy of PGT-A results between the two groups and analyzed potential contamination in the c-IVF insemination group. Results: A total of 320 blastocysts underwent PGT-A testing, with 179 blastocysts from c-IVF insemination and 141 from ICSI insemination. Considering participants' baseline characteristics and embryological outcomes, no significant differences were found between the two groups regarding infertility type, average age, body mass index, percentage of PGT-A indications, or quality of embryonic development. Regarding PGT-A results, all 320 biopsy samples were successfully analyzed, showing no statistical variance in chromosomal euploidy, abnormality, or mosaicism rates between the two insemination methods. No parental contamination was detected in the c-IVF insemination group. When assessing clinical outcomes, parameters such as biochemical pregnancy, clinical pregnancy, and miscarriage rates did not exhibit significant discrepancies between the two groups, and no misdiagnoses were reported during the study period. Conclusion: Embryo transfer and PGT-A results are not affected by potential parental contamination in frozen-thawed embryos conceived via c-IVF. PGT-A guided embryo transfer in thawed embryos conceived by c-IVF is a viable and clinically effective approach.


Asunto(s)
Aneuploidia , Criopreservación , Estudios de Factibilidad , Fertilización In Vitro , Pruebas Genéticas , Diagnóstico Preimplantación , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Embarazo , Diagnóstico Preimplantación/métodos , Adulto , Fertilización In Vitro/métodos , Criopreservación/métodos , Pruebas Genéticas/métodos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Transferencia de Embrión/métodos , Blastocisto , Índice de Embarazo , Masculino , Estudios Retrospectivos
3.
Oncol Res Treat ; : 1-32, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39293411

RESUMEN

INTRODUCTION: This study aimed to retrospectively analyze the response and prognosis factors for patients of lung adenocarcinoma with brain metastasis and epidermal growth factor receptor (EGFR) mutation, who were treated by EGFR-tyrosine kinase inhibitor (TKI) combined with brain radiotherapy (RT). METHODS: From Jan 2021 to Jan 2024, the clinicopathological data of lung adenocarcinoma patients were collected from the First Affiliated Hospital of Hebei North University. SPSS version 26.0 statistical software was used for statistical analysis. P < 0.05 was determined to be statistically significant. RESULTS: 105 patients were included. The 1, 2, 3-year overall survival (OS) rate was 82.9%, 61.2%, and 33.7%, respectively. 1, 2 ,3-year progression-free survival 1 (PFS1) rate was 62.7%, 36.6%, 22.1%. 1,2,3-year PFS2 rate was 80.8%, 54.6%, and 31.4%. The median OS, PFS1 and PFS2 was 29.8, 18.0 and 28.1 months, respectively. The COX multivariate analysis showed that gene mutation status and brain radiation dose were independent prognostic factors for OS; Gene mutation status, brain radiation dose, and response evaluation to initial treatment (response evaluation) are independent prognostic factors for PFS1; Clinical stage, gene mutation status, brain radiation dose, and response evaluation are independent prognostic factors for PFS2. CONCLUSION: TKI combined with brain radiotherapy is effective on lung adenocarcinoma patients with EGFR mutation and brain metastasis. Patients with 19 Del or 21 L858R mutation and brain radiation doses ≥ 40 Gy have longer OS, PFS1, and PFS2, and complete remission (CR) + partial remission (PR) is associated with longer PFS1 and PFS2, Patients in stage IVA have longer PFS2.

4.
Clin Transl Oncol ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320604

RESUMEN

PURPOSE: Studies have shown that the gut microbiota may affect anti-tumor immunity by regulating the host immune system and tumor microenvironment. To date, little is known about whether the gut microbiota underlies the occurrence of diffuse large B-cell lymphoma (DLBCL) and drug resistance. METHODS: In the present study, we compared the gut microbiota structure of fecal samples from 26 patients with primary DLBCL, 28 patients with relapsed and refractory (RR) DLBCL, and 30 healthy people. RESULTS: Notably, Fusobacteria (from phylum to species) was enriched in the primary group. A decrease of Fusobacterium and an increase of Enterococcus were found in the RR group. PICRUSt analysis found that genes related to cytochrome P450 were upregulated in the RR group compared to the primary group, which likely contributes to the occurrence of DLBCL and the formation of drug resistance. CONCLUSIONS: Our study provides further evidence for the relationship between gut microbiota and DLBCL and the formation of drug resistance, highlighting the potential significance of the bacterial variations may be used as new biomarkers of DLBCL.

5.
Sci Total Environ ; 954: 176517, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39341240

RESUMEN

Clarifying the spatial heterogeneity of the multiple climate-related risks has increasingly become a prerequisite for urban risk management and sustainability. As the datasets become more detailed in social attribute's representation at the fine scale within-city level, in contrast to those at a coarse region level, there is a continuous need to examine the spatial heterogeneity of integrated risk assessment. In this study, we applied the hazard-exposure-vulnerability framework to investigate the spatial variations of the integrations of urban heat stress and flooding strikes at the street block scale within Shenzhen, China. The findings showed approximately 16.85 % of the built-up areas experienced a strong dual pressure of heat and flooding, mostly concentrated in the street blocks constructed before 1990. Another 19.84 % of built-up areas exhibited a high level of heat risk, concentrated in the northern urban areas that developed in the recent period. While 26.28 % demonstrated a high level of flooding risk, located in the old urbanized areas. Such spatial variations of integrated risks resulted from the spatial mismatched hotspots among hazard, exposure, and vulnerability. The spatial heterogeneity of the integrated risk assessment suggests differentiated strategies to reduce the maladaptation of urban heat stress and flooding strike. The findings present opportunities to prioritize the street blocks and develop the most sustainable solutions.

7.
NPJ Clim Atmos Sci ; 7(1): 215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281887

RESUMEN

During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

8.
J Hematol Oncol ; 17(1): 60, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107807

RESUMEN

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.


Asunto(s)
Enfermedad de Castleman , Herpesvirus Humano 8 , Humanos , Enfermedad de Castleman/tratamiento farmacológico , Enfermedad de Castleman/virología , Enfermedad de Castleman/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Supervivencia sin Progresión , Adulto Joven , Adolescente
9.
Genes (Basel) ; 15(8)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39202382

RESUMEN

Spodoptera frugiperda poses a severe threat to crops, causing substantial economic losses. The increased use of chemical pesticides has led to resistance in S. frugiperda populations. Micro ribonucleic acids (MicroRNAs or miRNAs) are pivotal in insect growth and development. This study aims to identify miRNAs across different developmental stages of S. frugiperda to explore differential expression and predict target gene functions. High-throughput sequencing of miRNAs was conducted on eggs, 3rd instar larvae, pupae, and adults. Bioinformatics analyses identified differentially expressed miRNAs specifically in larvae, with candidate miRNAs screened to predict target genes, particularly those involved in detoxification pathways. A total of 184 known miRNAs and 209 novel miRNAs were identified across stages. Comparative analysis revealed 54, 15, and 18 miRNAs differentially expressed in larvae, compared to egg, pupa, and adult stages, respectively. Eight miRNAs showed significant differential expression across stages, validated by quantitative reverse transcription PCR (qRT-PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted target genes' functions, identifying eight differentially expressed miRNAs targeting 10 gene families associated with detoxification metabolism, including P450s, glutathione S-transferase (GSTs), ATP-binding cassette (ABC) transporters, and sodium channels. These findings elucidate the species-specific miRNA profiles and regulatory mechanisms of detoxification-related genes in S. frugiperda larvae, offering insights and strategies for effectively managing this pest.


Asunto(s)
Inactivación Metabólica , Larva , MicroARNs , Spodoptera , Animales , Spodoptera/genética , Spodoptera/metabolismo , Spodoptera/crecimiento & desarrollo , MicroARNs/genética , MicroARNs/metabolismo , Larva/genética , Larva/metabolismo , Larva/crecimiento & desarrollo , Inactivación Metabólica/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Regulación del Desarrollo de la Expresión Génica , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo
10.
J Am Heart Assoc ; 13(16): e034469, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39158576

RESUMEN

BACKGROUND: Multiple target-organ damages (TODs) in the same patient are common and further increase the risk of cardiovascular disease. However, the relationship between ambulatory central systolic blood pressure (SBP) and multiple TODs has yet to be explored. METHODS AND RESULTS: MobilO-Graph PWA was used to monitor the participants' ambulatory blood pressure, and the presence of left ventricular hypertrophy, carotid hypertrophy, and kidney injury were used to define TOD. Logistic regression analyses and receiver operating characteristic analyses were used to explore the correlation between SBP and TOD. Overall, 2018 nondialysis patients with chronic kidney disease were included and 580 (28.74%) had multiple TODs. Twenty-four-hour central SBP with c2 calibration exhibited a stronger correlation with the increasing number of TOD compared with 24-hour brachial SBP in ordinal logistic regression analyses. In the multivariable analyses with the presence of multiple TODs, the odds ratios were 1.786 (95% CI, 1.474-2.165; P<0.001) for 24-hour brachial SBP and 1.949 (95% CI, 1.605-2.366; P<0.001) for 24-hour central SBP with c2 calibration. The receiver operating characteristic analyses also showed that 24-hour central SBP with c2 calibration had higher discrimination than 24-hour brachial SBP regarding multiple TODs (P<0.001). In addition, using 130/135 mm Hg as the threshold for 24-hour brachial SBP/central SBP with c2 calibration to cross-classify, the prevalence of multiple TODs was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension, with no difference between the latter 2 conditions. CONCLUSIONS: Twenty-four-hour central SBP with c2 calibration was more associated with the presence of multiple TODs compared with 24-hour brachial SBP and was helpful in risk classification of multiple TODs among nondialysis patients with chronic kidney disease.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Persona de Mediana Edad , Presión Sanguínea/fisiología , Anciano , Factores de Riesgo , Medición de Riesgo/métodos , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertensión/fisiopatología , Hipertensión/epidemiología , Hipertensión/diagnóstico , Hipertensión/complicaciones , Factores de Tiempo , Estudios Transversales
11.
Med ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39151422

RESUMEN

BACKGROUND: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. METHODS: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. FINDINGS: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. CONCLUSIONS: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. FUNDING: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.

12.
Pathol Res Pract ; 261: 155459, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39083879

RESUMEN

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC classified as a molecularly defined RCC in the fifth edition of the WHO. Most gene alterations in patients with SDH-deficient RCC involve the SDHB subunit, with less involvement of the SDHC, SDHA, and SDHD subunits. Four cases of SDHA-deficient RCC have been reported in the literature, of which one case was associated with an NF2 gene mutation. Herein, we report six novel SDHA-deficient RCC cases, including two cases with NF2 gene mutations. In contrast to the typical morphology of SDH-deficient RCC, the six tumors mainly displayed glandular, sheet-like, or papillary growth patterns with prominent nucleoli (Grades 2-3), among which two cases with NF2 mutations had prominent nucleoli (Grade 3), large transparent vacuoles in the cytoplasm, and a large number of lymphocytes in the stroma. Six tumors showed negative immunohistochemical staining for SDHA and SDHB, and three cases presented with high expression of PD-L1. Second-generation sequencing revealed novel pathogenic somatic SDHA gene mutation and NF2 gene mutations in six and two tumors, respectively. Follow-up data were collected for the six patients with a follow-up time ranging from 7 to 268 months, and all six patients have survived to date. One patient received targeted therapy for tumor metastasis to the lungs after seven months, and another patient with an NF2 gene mutation received immunotherapy for lymph node metastasis revealed during surgery. SDHA-deficient RCCs with NF2 gene mutations have the ability to metastasize but might respond well to immunotherapy. For the first time, we report the largest number of SDHA-deficient RCC cases and comprehensively investigate their clinicopathological and molecular features to provide important guidance for diagnosis and clinical immunotherapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Succinato Deshidrogenasa , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Masculino , Femenino , Persona de Mediana Edad , Succinato Deshidrogenasa/deficiencia , Succinato Deshidrogenasa/genética , Mutación , Adulto , Anciano , Biomarcadores de Tumor/genética , Neurofibromina 2 , Complejo II de Transporte de Electrones
14.
Br J Haematol ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38706448

RESUMEN

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

16.
Hypertens Res ; 47(6): 1697-1706, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38553645

RESUMEN

The current research on the relationship between 24-h central pressure and 24-h brachial pressure with left ventricular hypertrophy (LVH) is characterised by limited sample size and inconsistent findings. Furthermore, the association has never been explored in chronic kidney disease (CKD). A multicentre, cross-sectional study among non-dialysis patients with CKD was conducted. All participants underwent brachial and central ambulatory blood pressure monitoring using MobilO-Graph PWA, while trained cardiologists performed echocardiography. In this study, 2117 non-dialysis patients with CKD were examined. 24-h central systolic blood pressure with c2 calibration (24-h c2SBP) demonstrated a stronger association with left ventricular mass index and LVH compared with 24-h brachial systolic blood pressure (24-h bSBP) in the univariate and multivariate regression analyses. The multivariate net reclassification index (NRI) analysis revealed that 24-h c2SBP exhibited greater discriminatory power over 24-h bSBP (NRI = 0.310, 95% CI [0.192-0.429], P < 0.001). Applying 130/135 mmHg as the threshold for 24-h bSBP/c2SBP to cross-classify, the patients were divided into concordant normotension (1509 individuals), isolated brachial hypertension (155 individuals), isolated central hypertension (11 individuals), and concordant hypertension (442 individuals). With concordant normotension as the reference, the multivariable-adjusted ORs were 0.954 (95% CI, 0.534-1.640; P = 0.870) for isolated brachial hypertension and 2.585 (95%CI, 1.841-3.633; P < 0.001) for concordant hypertension. Among non-dialysis patients with CKD, 24-h c2SBP exhibits greater efficacy in identifying the presence of LVH compared with 24-h bSBP. The presence of LVH was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Hipertrofia Ventricular Izquierda , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/fisiopatología , Persona de Mediana Edad , Estudios Transversales , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Anciano , Presión Sanguínea/fisiología , Adulto , Ecocardiografía , Hipertensión/fisiopatología , Hipertensión/complicaciones
17.
Genome Res ; 34(2): 326-340, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38428994

RESUMEN

Pacific Biosciences (PacBio) HiFi sequencing technology generates long reads (>10 kbp) with very high accuracy (<0.01% sequencing error). Although several de novo assembly tools are available for HiFi reads, there are no comprehensive studies on the evaluation of these assemblers. We evaluated the performance of 11 de novo HiFi assemblers on (1) real data for three eukaryotic genomes; (2) 34 synthetic data sets with different ploidy, sequencing coverage levels, heterozygosity rates, and sequencing error rates; (3) one real metagenomic data set; and (4) five synthetic metagenomic data sets with different composition abundance and heterozygosity rates. The 11 assemblers were evaluated using quality assessment tool (QUAST) and benchmarking universal single-copy ortholog (BUSCO). We also used several additional criteria, namely, completion rate, single-copy completion rate, duplicated completion rate, average proportion of largest category, average distance difference, quality value, run-time, and memory utilization. Results show that hifiasm and hifiasm-meta should be the first choice for assembling eukaryotic genomes and metagenomes with HiFi data. We performed a comprehensive benchmarking study of commonly used assemblers on complex eukaryotic genomes and metagenomes. Our study will help the research community to choose the most appropriate assembler for their data and identify possible improvements in assembly algorithms.


Asunto(s)
Metagenoma , Programas Informáticos , Análisis de Secuencia de ADN/métodos , Algoritmos , Metagenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
18.
Am J Hematol ; 99(4): 774-779, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38343062

RESUMEN

Jaktinib, a novel JAK and ACVR1 inhibitor, has exhibited promising results in treating patients with myelofibrosis (MF). ZGJAK002 is a Phase 2 trial aimed to assess the efficacy and safety of jaktinib 100 mg BID (N = 66) and 200 mg QD (N = 52) in JAK inhibitor-naive patients with intermediate- or high-risk MF. We herein present the long-term data with a median follow-up of 30.7 months. At data cutoff, 30.3% of patients in 100 mg BID and 28.8% in 200 mg QD were still continuing their treatment. The 100 mg BID group displayed a numerically higher best spleen response compared with the 200 mg QD group (69.7% vs. 46.2%), with 50.4% from the BID and 51.2% from the QD group maintaining spleen responses over 120 weeks. The 36-month survival rates were 78.2% in BID and 73.6% in QD group. The tolerability of jaktinib remained well, and common grade ≥3 adverse drug reactions included anemia (15.2% vs. 21.2%), thrombocytopenia (15.2% vs. 11.5%), and infectious pneumonia (10.6% vs. 1.9%) in BID and QD groups, respectively. By comparing the two groups, the incidence of adverse events (AEs) were similar, except for drug-related serious AEs (24.2% vs. 9.6%) and AEs leading to treatment discontinuation (15.2% vs. 7.7%), which were higher in BID group. The percentages of AEs resulting in death were comparable, with 6.1% in BID and 5.8% in QD group. These analyses further support the long-term durable efficacy and acceptable safety of jaktinib at 100 mg BID and 200 mg QD doses for treating MF.


Asunto(s)
Mielofibrosis Primaria , Humanos , Estudios de Seguimiento , Mielofibrosis Primaria/tratamiento farmacológico , Resultado del Tratamiento
19.
Br J Haematol ; 204(6): 2342-2350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38400570

RESUMEN

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Etopósido , Filgrastim , Movilización de Célula Madre Hematopoyética , Linfoma , Mieloma Múltiple , Polietilenglicoles , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Femenino , Masculino , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Adulto , Linfoma/tratamiento farmacológico , Linfoma/terapia , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Estudios Prospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Movilización de Célula Madre Hematopoyética/métodos , Adulto Joven , Adolescente
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