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Outcomes are poor in triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In the phase 3 KarMMa-3 (clinicaltrials.gov; NCT03651128) trial, patients with TCE RRMM and 2-4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary endpoint; 13.3 vs 4.4 months; P<.0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median (95% CI) was 41.4 (30.9-not reached [NR]) vs 37.9 (23.4-NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE RRMM. NCT03651128.
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BACKGROUND: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. METHODS: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from noninvading cells. We used this model to perform multiple transcriptomics analyses from independent donors to monitor endothelial gene expression changes. RESULTS: Single-cell population analyses, single-cell cluster analyses, and bulk RNA sequencing revealed common transcriptomic changes associated with invading cells. We also found that collagenase digestion used to isolate single cells upregulated the Fos proto-oncogene transcription factor. Exclusion of Fos proto-oncogene expressing cells revealed a gene signature consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis and included multiple tip cell markers. Upregulation of SNAI1 (snail family transcriptional repressor 1), PTGS2 (prostaglandin synthase 2), and JUNB (JunB proto-oncogene) protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated rounding 3, also known as RhoE, which has not yet been implicated in angiogenesis. Silencing rounding 3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for rounding 3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared with wild-type littermates. CONCLUSIONS: Validation of multiple genes, including rounding 3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.
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Perfilación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-fos , Transcriptoma , Proteínas de Unión al GTP rho , Animales , Humanos , Ratones , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Células Endoteliales/metabolismo , Perfilación de la Expresión Génica/métodos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica/genética , Fenotipo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Proteínas de Unión al GTP rho/genética , Transducción de Señal , Análisis de la Célula Individual , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genéticaRESUMEN
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease among neonates, with increasing morbidity and mortality. This study aims to investigate the effect and mechanism of lysine demethylase 3A (KDM3A) on hyperoxia-induced BPD. Hyperoxia-induced BPD mouse and alveolar epithelial cell models were constructed. The effects of hyperoxia on lung development were evaluated by histological and morphological analysis. The levels of KDM3A, E26 transformation specific-1 (ETS1), H3 lysine 9 dimethylation (H3K9me2), and endoplasmic reticulum (ER) stress-related indexes were quantified by RT-qPCR, Western blot, and IF staining. Cell apoptosis was assessed by flow cytometry and TUNEL staining. Transfection of oe-ETS1, oe-KDM3A, and sh-ETS1 was applied in hyperoxia-induced alveolar epithelial cells to explore the mechanism of the KDM3A/ETS1 axis in hyperoxia-induced apoptosis. KDM3A inhibitor IOX1 was applied to validate the in vivo effect of KDM3A in hyperoxia-induced BPD mice. The results displayed that hyperoxia-induced BPD mice showed reduced body weight, severe destruction of alveolar structure, decreased radial alveolar count (RAC), and increased mean linear intercept (MLI) and mean alveolar diameter (MAD). Further, hyperoxia induction down-regulated ETS1 expression, raised ER stress levels, and increased apoptosis rate in BPD mice and alveolar epithelial cells. However, transfection of oe-ETS1 improved the above changes in hyperoxia-induced alveolar epithelial cells. Moreover, transfection of oe-KDM3A up-regulated ETS1 expression, down-regulated H3K9me2 expression, inhibited ER stress, and reduced apoptosis rate in hyperoxia-induced alveolar epithelial cells. In addition, transfection of sh-ETS1 reversed the inhibitory effect of KDM3A on hyperoxia-induced apoptosis by regulating ER stress. In vivo experiments, KDM3A inhibitor IOX1 intervention further aggravated BPD in newborn mice. In a word, KDM3A alleviated hyperoxia-induced BPD in mice by promoting ETS1 expression.
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Displasia Broncopulmonar , Hiperoxia , Animales , Ratones , Animales Recién Nacidos , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Modelos Animales de Enfermedad , Hiperoxia/complicaciones , Hiperoxia/metabolismo , Hiperoxia/patología , Pulmón/metabolismo , Lisina/metabolismo , Factores de Transcripción/metabolismoRESUMEN
As a Brassica crop, Brassica napus typically has single flowers that contain four petals. The double-flower phenotype of rapeseed has been a desirable trait in China because of its potential commercial value in ornamental tourism. However, few double-flowered germplasms have been documented in B. napus, and knowledge of the underlying genes is limited. Here, B. napus D376 was characterized as a double-flowered strain that presented an average of 10.92 ± 1.40 petals and other normal floral organs. F1, F2 and BC1 populations were constructed by crossing D376 with a single-flowered line reciprocally. Genetic analysis revealed that the double-flower trait was a recessive trait controlled by multiple genes. To identify the key genes controlling the double-flower trait, bulk segregant analysis sequencing (BSA-seq) and RNA-seq analyses were conducted on F2 individual bulks with opposite extreme phenotypes. Through BSA-seq, one candidate interval was mapped at the region of chromosome C05: 14.56-16.17 Mb. GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in carbohydrate metabolic processes, notably starch and sucrose metabolism. Interestingly, five and thirty-six DEGs associated with floral development were significantly up- and down-regulated, respectively, in the double-flowered plants. A combined analysis of BSA-seq and RNA-seq data revealed that five genes were candidates associated with the double flower trait, and BnaC05.ERS2 was the most promising gene. These findings provide novel insights into the breeding of double-flowered varieties and lay a theoretical foundation for unveiling the molecular mechanisms of floral development in B. napus.
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Brassica napus , Flores , Fenotipo , RNA-Seq , Brassica napus/genética , Brassica napus/crecimiento & desarrollo , Flores/genética , Flores/crecimiento & desarrollo , Genes de Plantas , Regulación de la Expresión Génica de las Plantas , Mapeo Cromosómico , Perfilación de la Expresión GénicaRESUMEN
Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1âº, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity.
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Lupus Eritematoso Sistémico , Ratones , Animales , Ratones Endogámicos C57BL , Lupus Eritematoso Sistémico/genética , Autoinmunidad , Diferenciación Celular , Dosificación de Gen , Ratones Endogámicos MRL lprRESUMEN
PURPOSE: To investigate the efficacy and safety of repeated low-level red-light (RLRL) therapy combined with orthokeratology among children who, despite undergoing orthokeratology, exhibited an axial elongation of at least 0.50 mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov identifier, NCT04722874). PARTICIPANTS: Eligible children were 8-13 years of age with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters at the initial orthokeratology fitting examination and had annual axial length (AL) elongation of ≥0.50 mm despite undergoing orthokeratology. Forty-eight children were enrolled from March 2021 through January 2022, and the final follow-up was completed in March 2023. METHODS: Children were assigned randomly to the RLRL therapy combined with orthokeratology (RCO) group or to the orthokeratology group in a 2:1 ratio. The orthokeratology group wore orthokeratology lenses for at least 8 hours per night, whereas the RCO group received daily RLRL therapy twice daily for 3 minutes in addition to orthokeratology. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 follow-up after randomization using the modified intention-to-treat principle. RESULTS: Forty-seven children (97.9%) were included in the analysis (30 in the RCO group and 17 in the orthokeratology group). The mean axial elongation rate before the trial was 0.60 mm/year and 0.61 mm/year in the RCO and orthokeratology groups, respectively. After 12 months, the adjusted mean AL changes were -0.02 mm (95% confidence interval [CI], -0.08 to +0.03 mm) in the RCO group and 0.27 mm (95% CI, 0.19-0.34 mm) in the orthokeratology group. The adjusted mean difference in AL change was -0.29 mm (95% CI, -0.44 to -0.14 mm) between the groups. The percentage of children achieving an uncorrected visual acuity of more than 20/25 was similar in the RCO (64.3%) and orthokeratology (65.5%) groups (P = 0.937). CONCLUSIONS: Combining RLRL therapy with orthokeratology may offer a promising approach to optimize axial elongation control among children with myopia. This approach also potentially allows children to achieve satisfactory visual acuity, reducing daytime dependence on corrective eyewear. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Miopía , Procedimientos de Ortoqueratología , Refracción Ocular , Humanos , Procedimientos de Ortoqueratología/métodos , Niño , Masculino , Femenino , Miopía/fisiopatología , Miopía/terapia , Adolescente , Método Simple Ciego , Refracción Ocular/fisiología , Longitud Axial del Ojo , Agudeza Visual/fisiología , Resultado del Tratamiento , Fototerapia/métodos , Terapia Combinada , Estudios de SeguimientoRESUMEN
Terahertz (THz) radiation from air plasma in the presence of pre-plasma in a collinear geometry is investigated experimentally, where the pre-plasma is formed by a pre-pulse with a Gaussian beam profile and the measured THz radiation is driven by a main laser pulse. The pre-plasma has a de-focusing effect for the main pulse passing through it, which reduces the effective length of the plasma filament formed by the main laser pulse for THz radiation. It is found that only the part not overlapped by the pre-plasma can actually produce THz radiation. Thus, the amplitude of the THz pulse driven by the main pulse can be modified by changing the spatial separation between two plasma filaments. The experimental observations are qualitatively in agreement with our numerical simulation results. It is also found that the change of the time delay between the pre-pulse and the main pulse does not change the THz radiation amplitude for a given spatial separation. This study suggests a practical way for the manipulation of THz waves through an interaction between laser plasma filaments.
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We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.
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Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Biomarcadores/análisis , Proyectos de Investigación , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.
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Lesión Renal Aguda , Coagulación Intravascular Diseminada , Fiebre Hemorrágica con Síndrome Renal , Humanos , Estudios Retrospectivos , Pruebas de Coagulación Sanguínea , Pronóstico , Fibrinógeno , Coagulación Intravascular Diseminada/etiologíaRESUMEN
There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.
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Biomarcadores de Tumor , Neoplasias de las Glándulas Sudoríparas , Microambiente Tumoral , Humanos , Estudios Retrospectivos , Neoplasias de las Glándulas Sudoríparas/genética , Neoplasias de las Glándulas Sudoríparas/patología , Neoplasias de las Glándulas Sudoríparas/terapia , Neoplasias de las Glándulas Sudoríparas/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Mutación , Resultado del Tratamiento , Linfocitos Infiltrantes de Tumor/inmunología , Antígeno B7-H1 , Inmunoterapia/métodos , Adulto Joven , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
BACKGROUND: Severe acute pancreatitis (SAP) is associated with tremendous systemic inflammation, T-helper 17 (Th17) cells, and regulatory T (Treg) cells play an essential role in the inflammatory responses. Meanwhile, soluble fibrinogen-like protein 2 (Sfgl2) is a critical immunosuppressive effector cytokine of Treg cells and modulates immune responses. However, the impact of SAP induction on Sfgl2 expression and the role of Sfgl2 in immunomodulation under SAP conditions are largely unknown. METHODS: A taurocholate-induced mouse SAP model was established. The ratios of CD4+CD25+Foxp3+ Treg cells or CD4+IL-17+ Th17 cells in blood and pancreatic tissues as well as surface expression of CD80, CD86, and major histocompatibility complex class II (MHC-II) were determined by flow cytometry. Gene mRNA expression was determined by qPCR. Serum amylase and soluble factors were quantitated by commercial kits. Bone marrow-derived dendritic cells (DCs) were generated, and NF-κB/p65 translocation was measured by immunofluorescence staining. RESULTS: SAP induction in mice decreased the Th17/Treg ratio in the pancreatic tissue and increased the Th17/Treg ratio in the peripheral blood. In addition, SAP was associated with a reduced level of Sfgl2 in the pancreatic tissue and blood: higher levels of serum IL-17, IL-2, IFN-α, and TNF-α, and lower levels of serum IL-4 and IL-10. Furthermore, the SAP-induced reduction in Sfgl2 expression was accompanied by dysregulated maturation of bone marrow-derived DCs. CONCLUSIONS: SAP causes reduced Sfgl2 expression and Th17/Treg imbalance, thus providing critical insights for the development of Sfgl2- and Th17/Treg balance-targeted immunotherapies for patients with SAP.
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Modelos Animales de Enfermedad , Fibrinógeno , Pancreatitis , Linfocitos T Reguladores , Ácido Taurocólico , Células Th17 , Animales , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Pancreatitis/inmunología , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Ratones , Fibrinógeno/metabolismo , Masculino , Ratones Endogámicos C57BL , Regulación hacia Abajo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Enfermedad Aguda , Páncreas/inmunología , Páncreas/patología , Páncreas/metabolismoRESUMEN
Honey bees utilize queen mandibular pheromone (QMP) for maintaining social hierarchy and colony development. In controlled cage studies, synthetic QMP is often introduced to mimic natural conditions. However, questions have arisen about the effects of QMP on nosema disease studies. This short report identifies significant early-stage suppression effects of QMP on Nosema (Vairimorpha) ceranae infections. QMP was found to significantly lower infection rates below the reported infectious dose for 50 % infectivity (ID50) and to slow disease development in a dose-independent manner. These effects diminished at doses exceeding ID100. We recommend that studies investigating treatment effects using caged bees avoid QMP to ensure unambiguous results. Additionally, employing multiple infectious doses with shorter incubation times would be useful for evaluating other treatments that may have subtle effects. Furthermore, our findings support previous field studies suggesting that queen replacement reduces nosema disease at levels similar to treatment with fumagillin.
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Nosema , Feromonas , Animales , Nosema/efectos de los fármacos , Nosema/fisiología , Abejas/microbiología , Abejas/efectos de los fármacos , Feromonas/farmacologíaRESUMEN
This paper comprehensively analyzes the caregiver burden and its influencing factors on primary caregivers in autologous hematopoietic stem cell transplantation (Auto-HSCT) with bendamustine preconditioning. Auto-HSCT refers to the transplantation of cells back to the patient, aiming to eliminate tumor cells and prolong the patient's life. Bendamustine, while enhancing the success rate of transplantation, has drawn considerable attention to the primary caregivers of patients. Due to the complex nature of the transplantation process, patients have diverse caregiving needs, which caregivers must address to support the entire treatment journey. The caregiver burden of primary caregivers is influenced by various factors, including the patient's disease condition, various aspects of the caregiver as an individual, and psychological factors. The article emphasizes the need for personalized care plans and psychological support to minimize caregiver burden and improve overall quality of life. This study has positive implications for optimizing the implementation of Auto-HSCT therapy.
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Objective: To analyze the potential factors influencing the diagnostic capability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and provide medication treatment recommendations for patients with pancreatic solid mass lesions. Methods: A retrospective analysis was conducted on clinical data of 92 patients with pancreatic solid mass lesions who underwent EUS-FNA examination after detection by imaging studies. The diagnostic effectiveness of EUS-FNA was evaluated based on cytological or histological examination results. Logistic regression analysis was subsequently performed to analyze the potential factors influencing the diagnostic capability of EUS-FNA in patients with pancreatic solid mass lesions. Results: EUS-FNA was successfully performed in all 92 patients, with a puncture success rate of 100.00%. Only one patient experienced transient hyperamylasemia, which resolved with conservative treatment. No other serious complications were observed. Among the 92 patients, 70 patients obtained a definite diagnosis after EUS-FNA (Group A), while 22 patients did not achieve a definite diagnosis (Group B) after the procedure. Univariate analysis showed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were significantly different between Group A and Group B (P < .05). Multivariate logistic regression analysis revealed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions (P < .05). Conclusion: EUS-FNA has a high diagnostic value in the evaluation of solid pancreatic lesions. Lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method are potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions. In terms of medical treatment, specific treatment methods and drug choices should be based on a comprehensive evaluation of the nature of the patient's lesions and the severity of the condition.
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Antibiotics are frequently employed to control bacterial diseases in honeybees, but their broad-spectrum action can disrupt the delicate balance of the gut microbiome, leading to dysbiosis. This imbalance in the gut microbiota of honeybees adversely affects their physiological health and weakens their resistance to pathogens, including viruses that significantly threaten honeybee health. In this study, we investigated whether tetracycline-induced gut microbiome dysbiosis promotes the replication of Israeli acute paralysis virus (IAPV), a key virus associated with colony losses and whether IAPV infection exacerbates gut microbiome dysbiosis. Our results demonstrated that tetracycline-induced gut microbiome dysbiosis increases the susceptibility of honeybees to IAPV infection. The viral titer in worker bees with antibiotic-induced gut microbiome dysbiosis prior to IAPV inoculation was significantly higher than in those merely inoculated with IAPV. Furthermore, we observed a synergistic effect between tetracycline and IAPV on the disruption of the honeybee gut microbiome balance. The progression of IAPV replication could, in turn, exacerbate antibiotic-induced gut microbiome dysbiosis in honeybees. Our research provides novel insights into the role of the gut microbiota in host-virus interactions, emphasizing the complex interplay between antibiotic use, gut microbiome health, and viral susceptibility in honeybees. We highlight the crucial role of a balanced gut microbiota in honey bees for their immune response against pathogens and emphasize the importance of careful, safe antibiotic use in beekeeping to protect these beneficial microbes.
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Antibacterianos , Dicistroviridae , Disbiosis , Microbioma Gastrointestinal , Tetraciclina , Animales , Abejas/virología , Abejas/microbiología , Abejas/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Disbiosis/inducido químicamente , Disbiosis/virología , Tetraciclina/farmacología , Tetraciclina/toxicidad , Dicistroviridae/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/toxicidadRESUMEN
BACKGROUND: The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. METHODS: This hospital-based, cross-sectional study was conducted at the Third People's Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. RESULTS: The study included participants primarily between the ages of 20-40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. CONCLUSION: Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.
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COVID-19 , Competencia Clínica , Entrenamiento Simulado , Humanos , COVID-19/epidemiología , Estudios Transversales , China , Femenino , Masculino , Adulto , SARS-CoV-2 , Adulto Joven , Cuerpo Médico de Hospitales/educación , PandemiasRESUMEN
The accurate and efficient detection of defective insulators is an essential prerequisite for ensuring the safety of the power grid in the new generation of intelligent electrical system inspections. Currently, traditional object detection algorithms for detecting defective insulators in images face issues such as excessive parameter size, low accuracy, and slow detection speed. To address the aforementioned issues, this article proposes an insulator defect detection model based on the lightweight Faster R-CNN (Faster Region-based Convolutional Network) model (Faster R-CNN-tiny). First, the Faster R-CNN model's backbone network is turned into a lightweight version of it by substituting EfficientNet for ResNet (Residual Network), greatly decreasing the model parameters while increasing its detection accuracy. The second step is to employ a feature pyramid to build feature maps with various resolutions for feature fusion, which enables the detection of objects at various scales. In addition, replacing ordinary convolutions in the network model with more efficient depth-wise separable convolutions increases detection speed while slightly reducing network detection accuracy. Transfer learning is introduced, and a training method involving freezing and unfreezing the model is employed to enhance the network's ability to detect small target defects. The proposed model is validated using the insulator self-exploding defect dataset. The experimental results show that Faster R-CNN-tiny significantly outperforms the Faster R-CNN (ResNet) model in terms of mean average precision (mAP), frames per second (FPS), and number of parameters.
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Supercritical carbon dioxide (SCCO2) is a non-toxic and environmentally friendly fluid and has been used in polymerization reactions, processing, foaming, and plasticizing of polymers. Exploring the behavior and data of SCCO2 sorption and dissolution in polymers provides essential information for polymer applications. This study investigated the sorption and diffusion of SCCO2 into polyetherimide (PEI). The sorption and desorption processes of SCCO2 in PEI samples were measured in the temperature range from 40 to 60 °C, the pressure range from 20 to 40 MPa, and the sorption time from 0.25 to 52 h. This study used the ex situ gravimetric method under different operating conditions and applied the Fickian diffusion model to determine the mass diffusivity of SCCO2 during sorption and desorption processes into and out of PEI. The equilibrium mass gain fraction of SCCO2 into PEI was reported from 9.0 wt% (at 60 °C and 20 MPa) to 12.8 wt% (at 40 °C and 40 MPa). The sorption amount increased with the increasing SCCO2 pressure and decreased with the increasing SCCO2 temperature. This study showed the crossover phenomenon of equilibrium mass gain fraction isotherms with respect to SCCO2 density. Changes in the sorption mechanism in PEI were observed when the SCCO2 density was at approximately 840 kg/m3. This study qualitatively performed FTIR analysis during the SCCO2 desorption process. A CO2 antisymmetric stretching mode was observed near a wavenumber of 2340 cm-1. A comparison of loss modulus measurements of pure and SCCO2-treated PEI specimens showed the shifting of loss maxima. This result showed that the plasticization of PEI was achieved through the sorption process of SCCO2.
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Children obesity is a serious public health problem drawing much attention around the world. Recent research indicated that gut microbiota plays a vital role in children obesity, and disturbed gut microbiota is a prominent characteristic of obese children. Diet and exercise are efficient intervention for weight loss in obesity children, however, how the gut microbiota is modulated which remains largely unknown. To characterize the feature of gut microbiota in obese children and explore the effect of dietary and exercise on gut microbiota in simple obese children, 107 healthy children and 86 obese children were recruited, and among of the obese children 39 received the dietary-exercise combined weight loss intervention (DEI). The gut microbiota composition was detected by the 16S amplicon sequencing method. The gut microbiota composition was significantly different between obese children and the healthy cohort, and DEI significantly reduced the body weight and ameliorated the gut microbiota dysbiosis. After DEI, the abundance of the Akkermansia muciniphila was increased, while the abundance of the Sutterella genus was decreased in simple obese children. Our results may provide theoretical reference for future personalized obesity interventions based on gut microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01088-3.