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1.
Anal Bioanal Chem ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251426

RESUMEN

Quantitation of BCR-ABL1 with the quantitative reverse transcriptase polymerase chain reaction (RT-PCR) is very important in monitoring chronic myeloid leukemia (CML), which relies on an RNA reference material. A genomic RNA reference material (RM) containing the BCR-ABL1 P210 fusion mutation was developed, and an absolute quantitative method based on one-step reverse transcription digital PCR (RT-dPCR) was established for characterizing the RM. The proposed dPCR method demonstrates high accuracy and excellent analytical sensitivity, as shown by the linear relationship (0.94 < slope < 1.04, R2≧0.99) between the measured and nominal values of b2a2, b3a2, and ABL1-ref within the dynamic range (104-101 copies/reaction). Homogeneity and stability assessment based on dPCR indicated that the RM was homogeneous and stable for 24 months at -80 °C. The RM was used to evaluate inter-laboratory reproducibility in eight different laboratories, demonstrating that participating laboratories could consistently produce copy concentrations of b3a2 and ABL1-ref, as well as the BCR-ABL1/ABL1 ratio (CV < 2.0%). This work suggests that the RM can be employed in establishing metrological traceability for detecting mutations in the BCR-ABL1 fusion gene, as well as in quality control for testing laboratories.

2.
MethodsX ; 13: 102843, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39101121

RESUMEN

Event of the disastrous scenarios are actively discussed on microblogging platforms like Twitter which can lead to chaotic situations. In the era of machine learning and deep learning, these chaotic situations can be effectively controlled by developing efficient methods and models that can assist in classifying real and fake tweets. In this research article, an efficient method named BERT Embedding based CNN model with RMSProp Optimizer is proposed to effectively classify the tweets related disastrous scenario. Tweet classification is carried out via some of the popular the machine learning algorithms such as logistic regression and decision tree classifiers. Noting the low accuracy of machine learning models, Convolutional Neural Network (CNN) based deep learning model is selected as the primary classification method. CNNs performance is improved via optimization of the parameters with gradient based optimizers. To further elevate accuracy and to capture contextual semantics from the text data, BERT embeddings are included in the proposed model. The performance of proposed method - BERT Embedding based CNN model with RMSProp Optimizer achieved an F1 score of 0.80 and an Accuracy of 0.83. The methodology presented in this research article is comprised of the following key contributions:•Identification of suitable text classification model that can effectively capture complex patterns when dealing with large vocabularies or nuanced language structures in disaster management scenarios.•The method explores the gradient based optimization techniques such as Adam Optimizer, Stochastic Gradient Descent (SGD) Optimizer, AdaGrad, and RMSprop Optimizer to identify the most appropriate optimizer that meets the characteristics of the dataset and the CNN model architecture.•"BERT Embedding based CNN model with RMSProp Optimizer" - a method to classify the disaster tweets and capture semantic representations by leveraging BERT embeddings with appropriate feature selection is presented and models are validated with appropriate comparative analysis.

3.
Transl Pediatr ; 13(7): 1086-1096, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39144439

RESUMEN

Background: Parameningeal rhabdomyosarcoma (PM-RMS) accounts for about 20% of all rhabdomyosarcoma (RMS) cases. At present, most research on PM-RMS has been conducted in Europe and the United States of America, and research in China has been very limited. This study sought to analyze the clinical outcomes and prognostic factors of PM-RMS in children and adolescents from two consecutive protocols at Beijing Children's Hospital (BCH). Methods: A total of 80 patients aged up to 18 years with previously untreated PM-RMS who had received treatment under two consecutive protocols [i.e., either the BCH-RMS-2006 protocol or the Chinese Children Cancer Group (CCCG)-RMS-2016 protocol] were included in the statistical analysis. The Kaplan-Meier method was used for the survival analysis, and Cox regression was used for the univariate and multivariate analyses. Results: Of the 80 patients enrolled in the study, 69 (86.2%) had meningeal invasion (MI). Of these 69 MI patients, 18 (22.5%) had cranial nerve palsy (CNP), 64 (80.0%) had cranial base bone erosion (CBBE), 25 (31.3%) had intracranial extension (ICE), and 2 (2.5%) had positive cerebrospinal fluid (CSF) tumor cells. The median follow-up time was 20.5 months (range, 5-100 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 51.7% and 45.6%, respectively. The 5-year OS rates of the patients who received the BCH-RMS-2006 protocol (18/80, 22.5%) and the CCCG-RMS-2016 protocol (62/80, 77.5%) were 33.3% and 57.0%, respectively (P<0.05), while the PFS rates of these patients were 22.2% and 53.6%, respectively (P<0.05). In relation to the PM-RMS patients with MI, the 5-year OS rates were 21.4% and 52.7%, and the 5-year PFS rates were 14.3% and 51.1% for the patients who received the old and new regimens, respectively (P<0.05). The extent of surgical resection had no significant effect on survival. The multivariate analysis showed that the coexistence of CBBE and ICE, no radiotherapy, a poor response to induction chemotherapy, and the BCH-RMS-2006 protocol were risk factors affecting PFS and OS. Conclusions: Of the patients examined in this study, those with PM-RMS with CBBE accompanied by ICE had the worst prognosis. The patients with MI benefited from intensive chemotherapy combined with radiation therapy, but the effect of surgery was very limited.

4.
Heliyon ; 10(13): e33082, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027495

RESUMEN

Monitoring of groundwater (GW) resources in coastal areas is vital for human needs, agriculture, ecosystems, securing water supply, biodiversity, and environmental sustainability. Although the utilization of water quality index (WQI) models has proven effective in monitoring GW resources, it has faced substantial criticism due to its inconsistent outcomes, prompting the need for more reliable assessment methods. Therefore, this study addressed this concern by employing the data-driven root mean squared (RMS) models to evaluate groundwater quality (GWQ) in the coastal Bhola district near the Bay of Bengal, Bangladesh. To enhance the reliability of the RMS-WQI model, the research incorporated the extreme gradient boosting (XGBoost) machine learning (ML) algorithm. For the assessment of GWQ, the study utilized eleven crucial indicators, including turbidity (TURB), electric conductivity (EC), pH, total dissolved solids (TDS), nitrate (NO3 -), ammonium (NH4 +), sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), and iron (Fe). In terms of the GW indicators, concentration of K, Ca and Mg exceeded the guideline limit in the collected GW samples. The computed RMS-WQI scores ranged from 54.3 to 72.1, with an average of 65.2, categorizing all sampling sites' GWQ as "fair." In terms of model reliability, XGBoost demonstrated exceptional sensitivity (R2 = 0.97) in predicting GWQ accurately. Furthermore, the RMS-WQI model exhibited minimal uncertainty (<1 %) in predicting WQI scores. These findings implied the efficacy of the RMS-WQI model in accurately assessing GWQ in coastal areas, that would ultimately assist regional environmental managers and strategic planners for effective monitoring and sustainable management of coastal GW resources.

5.
J Fluoresc ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985396

RESUMEN

This study focuses on the design and synthesis of two novel coordination polymers (CPs), named 1 and 2, with excellent fluorescent properties. Their structures were characterized by X-ray single-crystal diffraction, revealing that both materials exhibit promising fluorescence performance, indicating their potential as fluorescent detection tools. Additionally, 1 was chosen to be combined with chitosan (CS), resulting in the successful fabrication of a biodegradable and non-toxic efficient drug carrier, termed CS-1@Cisplatin. This carrier possesses a large surface area and good solubility, enabling sustained drug release to target cells. Given that CXC motif chemokine receptor type 4 (CXCR4) is a key marker gene highly expressed in Rhabdomyosarcoma (RMS) cells and tissues, RMS was chosen as the biological model for testing. The results demonstrated that CS-1@Cisplatin effectively inhibited the invasiveness of RMS cells by significantly suppressing CXCR4 expression. Therefore, the system shows great potential for applications in RMS treatment, biometrics, and drug delivery, particularly in its unique advantage of targeting RMS by inhibiting the key marker gene CXCR4.

6.
Res Pract Thromb Haemost ; 8(4): 102467, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39040518

RESUMEN

Background: Coagulopathies are frequently observed in alveolar rhabdomyosarcoma (ARMS), with disseminated intravascular coagulation (DIC) being the most common presentation. However, hyperfibrinolysis represents a distinct but often overlapping and potentially life-threatening subset of coagulation disorders that requires specific diagnostic and management approaches. Key Clinical Question: How can clinicians identify hyperfibrinolysis and what are the implications for management? Clinical Approach: This case report describes a 25-year-old man with metastatic ARMS arising from the prostate who developed persistent gross hematuria one week after initiating chemotherapy. A comprehensive coagulation workup was performed, including assessment of platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin degradation products. Management included repletion of fibrinogen and the use of anti-fibrinolytic agents. Conclusion: Recognizing hyperfibrinolysis in ARMS patients is crucial for appropriate management. Clinicians should maintain a high index of suspicion for hyperfibrinolysis in ARMS patients presenting with severe coagulation abnormalities, particularly those with prostatic involvement or undergoing chemotherapy. In cases of primary hyperfibrinolysis, antifibrinolytic agents may be considered, whereas they are generally contraindicated in DIC.

7.
Heliyon ; 10(13): e33877, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39071645

RESUMEN

In the field of educational sciences, combining various research studies is essential for the development of key competencies such as digital and mathematical literacy. However, there is a research gap in understanding the challenges of implementing the Reading, Mind Mapping, and Sharing (RMS) teaching model in Indonesian schools, which requires a model customised for the unique context of the Indonesian education system. The objective of this research is to assess the impact of the RMS teaching model on students' digital and mathematical literacy. The study employed a quasi-experimental design, consisting of two experimental classes and one control class. The first experimental class used the RMS teaching model with brainstorming techniques. The second experimental class used the RMS teaching model without brainstorming. The control class followed standard instruction based on the school curriculum. During the even semester, a total of 96 secondary school students from two different schools in Bandar Lampung, a province in Indonesia, participated in both the experimental and control groups. Data collection was carried out using a questionnaire and a test. To analyse the data, Winstep and SPSS applications were used. The study's findings supported for the effectiveness of the RMS teaching model combined with the brainstorming method in enhancing students' mathematical literacy and digital literacy. Students who were taught this approach demonstrated higher mathematical literacy skills compared to those who received instruction using the RMS teaching model and direct instruction methods. This model can act as a guide for teachers to modify their approaches creating a captivating learning atmosphere that matches the requirements of students.

8.
Appl Radiat Isot ; 211: 111414, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38925035

RESUMEN

Measurement of independent isomeric yield ratios (IR) of 128,130,132Sb, 131,133Te, 132.134,136I, 135Xe and 138Cs have been carried out for the first time in the epi-cadmium neutron induced fission of 239Pu by using an off-line gamma-ray spectrometric technique. The average neutron energy () of the epi-cadmium reactor neutron spectrum is 1.9 MeV. From the IR values, root mean square fragment angular momenta (JRMS) were deduced by using spin dependent statistical model analysis. Effect of nuclear structure on JRMS values was examined. The present data in the epi-cadmium neutron induced fission of 239Pu were compared with the similar data in the thermal neutron induced fission of 239Pu to examine the role of excitation energy on JRMS values.

9.
J AOAC Int ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38917406

RESUMEN

BACKGROUND: The Mettler-Toledo 7000RMS analyzer is a Bio-Fluorescent Particle Counter (BFPC) used to monitor real-time bioburden results from Purified Water (PW). OBJECTIVE: Validation of the analyzer using 13 microorganisms and a low-intensity, fluorescent, polystyrene bead. METHODS: During the execution of the validation, a laboratory water system that met Purified Water (PW) quality standards was connected to the 7000RMS, and a syringe pump was used to introduce various concentrations of microorganisms and fluorescent polystyrene beads to the analyzer. Samples were collected and tested via the traditional Membrane Filtration (MF) method and the Colony Forming Unit (CFU) plate count results were compared to the Auto-Fluorescent Unit (AFU) of the 7000RMS analyzer. The validation study was designed to follow the guidance in United States Pharmacopeia (USP) Chapter <1223 > (1), European Pharmacopeia (EP) Chapter 5.1.6 (2), PDA Technical Report 33 (3). Concepts and strategies were adapted from EP Chapter 2.6.12 Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests, EP 10.2 (4), European Pharmacopeia Chapter 2.6.1 Sterility, EP 10.2 (5), USP Chapter <61> Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests (6), USP Chapter <71> Sterility Tests (7), Japanese Pharmacopoeia (JP) General Information Chapter G8 Water: Quality Control of Water for Pharmaceutical Use (8). RESULTS AND CONCLUSION: All pre-determined validation acceptance criteria for Accuracy, Specificity, Precision, Limit of Detection (LOD), Limit of Quantitation (LOQ), Linearity, and Range were met. Further, the 7000RMS demonstrated Performance Equivalence to the MF method per USP <1223> but characteristically lacked correlation to the CFU. HIGHLIGHTS: This validation approach highlights the superior capabilities of the 7000RMS when compared against the traditional compendial MF testing method for PW.

11.
Cancers (Basel) ; 16(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38730605

RESUMEN

Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells' phenotype. Delivery of exosomal miR-1246 targets GSK3ß and promotes ß-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.

12.
Front Oncol ; 14: 1387735, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720807

RESUMEN

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

13.
BMC Bioinformatics ; 25(1): 191, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750423

RESUMEN

BACKGROUND: The application of reduced metagenomic sequencing approaches holds promise as a middle ground between targeted amplicon sequencing and whole metagenome sequencing approaches but has not been widely adopted as a technique. A major barrier to adoption is the lack of read simulation software built to handle characteristic features of these novel approaches. Reduced metagenomic sequencing (RMS) produces unique patterns of fragmentation per genome that are sensitive to restriction enzyme choice, and the non-uniform size selection of these fragments may introduce novel challenges to taxonomic assignment as well as relative abundance estimates. RESULTS: Through the development and application of simulation software, readsynth, we compare simulated metagenomic sequencing libraries with existing RMS data to assess the influence of multiple library preparation and sequencing steps on downstream analytical results. Based on read depth per position, readsynth achieved 0.79 Pearson's correlation and 0.94 Spearman's correlation to these benchmarks. Application of a novel estimation approach, fixed length taxonomic ratios, improved quantification accuracy of simulated human gut microbial communities when compared to estimates of mean or median coverage. CONCLUSIONS: We investigate the possible strengths and weaknesses of applying the RMS technique to profiling microbial communities via simulations with readsynth. The choice of restriction enzymes and size selection steps in library prep are non-trivial decisions that bias downstream profiling and quantification. The simulations investigated in this study illustrate the possible limits of preparing metagenomic libraries with a reduced representation sequencing approach, but also allow for the development of strategies for producing and handling the sequence data produced by this promising application.


Asunto(s)
Metagenoma , Metagenómica , Programas Informáticos , Metagenoma/genética , Metagenómica/métodos , Humanos , Análisis de Secuencia de ADN/métodos , Microbioma Gastrointestinal/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
14.
BMC Med ; 22(1): 158, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38616269

RESUMEN

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.


Asunto(s)
Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Discapacidad Intelectual , Anomalías Dentarias , Humanos , Animales , Ratones , Facies , Bulbo Olfatorio , Modelos Animales de Enfermedad
15.
BMC Neurol ; 24(1): 138, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664640

RESUMEN

BACKGROUND: Physical fatigue is one of the most disabling symptoms in people with Multiple Sclerosis (PwMS). Several factors might influence the development of fatigue, such as gender, education, body mass index (BMI), Expanded Disability Status Scale (EDSS), disease duration, working status (Ws), physiotherapy (Ph), and disease-modifying therapies (DMTs). Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a patient-reported outcome (PRO) that allows one to define the impact of fatigue in PwMS clearly. This study aimed to assess fatigue impact on PwMS by using FSIQ-RMS. METHODS: The participants were enrolled from May to July 2021 in MS Centers of Sant'Andrea Hospital and Policlinico Umberto I Hospital in Rome. Fatigue was evaluated using the FSIQ-RMS, validated, and culturally adapted in Italian. Clinical and demographic data were collected at the same time. RESULTS: We enrolled 178 PwMS [Female 74.16%; RMS 82.58%, SPMS 17.52%]. FSIQ-RMS scores were significantly correlated with EDSS (p-value < 0.01). Analysis of variance between means showed a statistically significant difference between the BMI groups at the 24hours_FSIQ-RMS score and the 7days_FSIQ-RMS score (p < 0.01), with the lower BMI group having the highest scores. Furthermore, perceived fatigue significantly improved both in subjects performing Ph (p < 0.05) and in those who actively work (p < 0.01). CONCLUSIONS: The use of FSIQ-RMS in a real-world setting confirmed that underweight and high levels of disability are closely related to fatigue. In addition, Ph and active Ws are strongly correlated with fatigue in PwMS.


Asunto(s)
Fatiga , Encuestas Epidemiológicas , Esclerosis Múltiple , Percepción , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Estudios Transversales , Fatiga/etiología , Fatiga/psicología , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Modalidades de Fisioterapia , Índice de Masa Corporal , Análisis de Varianza , Correlación de Datos , Factores de Tiempo , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Ciudad de Roma , Reproducibilidad de los Resultados , Lenguaje , Delgadez/complicaciones , Evaluación de la Discapacidad
16.
Biomed Pharmacother ; 174: 116562, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626518

RESUMEN

Rhabdomyosarcoma (RMS), a mesenchymal tumor occurring in the soft tissue of children, is associated with a defect in differentiation. This study unveils a novel anti-tumor mechanism of dimethylaminomicheliolide (DMAMCL), which is a water-soluble derivative of Micheliolide. First, we demonstrate that DMAMCL inhibits RMS cell growth without obvious cell death, leading to morphological alterations, enhanced expression of muscle differentiation markers, and a shift from a malignant to a more benign metabolic phenotype. Second, we detected decreased expression of DLL1 in RMS cells after DMAMCL treatment, known as a pivotal ligand in the Notch signaling pathway. Downregulation of DLL1 inhibits RMS cell growth and induces morphological changes similar to the effects of DMAMCL. Furthermore, DMAMCL treatment or loss of DLL1 expression also inhibits RMS xenograft tumor growth and augmented the expression of differentiation markers. Surprisingly, in C2C12 cells DMAMCL treatment or DLL1 downregulation also induces cell growth inhibition and an elevation in muscle differentiation marker expression. These data indicated that DMAMCL induced RMS differentiation and DLL1 is an important factor for RMS differentiation, opening a new window for the clinical use of DMAMCL as an agent for differentiation-inducing therapy for RMS treatment.


Asunto(s)
Proteínas de Unión al Calcio , Diferenciación Celular , Proliferación Celular , Regulación hacia Abajo , Rabdomiosarcoma , Diferenciación Celular/efectos de los fármacos , Rabdomiosarcoma/patología , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/metabolismo , Animales , Regulación hacia Abajo/efectos de los fármacos , Humanos , Línea Celular Tumoral , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Proliferación Celular/efectos de los fármacos , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Desnudos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antineoplásicos/farmacología
17.
Yakugaku Zasshi ; 144(4): 353-357, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38556307

RESUMEN

In Japan, quantitative NMR (qNMR) has already been recognized as a standard method for determining the purity of quantitative samples not only in the Japanese Pharmacopoeia and the Japanese Standards and Specifications for Food Additives but also in the Japanese Industrial Standard (JIS K 0138: 2018). However, since there was no consensus on the establishment of a standard method, the international standardization of qNMR was initiated based on a proposal from Japan. After three years of discussion among experts, International Organization for Standardization/Technical Committee on Food (ISO/TC34) published ISO 24583: 2022 "Quantitative nuclear magnetic resonance spectroscopy-Purity determination of organic compounds used for foods and food products-General requirements for 1H-NMR internal standard method." Publication of this standard has resulted in an internationally agreed upon set of requirements for purity determination using qNMR. New technologies emerge from the cycle of basic research, practical use, and standardization, and qNMR is no exception. A novel chromatographic quantification method based on relative molar sensitivity (RMS) is now being put into practical use. The RMS of an analyte with respect to a different reference substance can be determined by using qNMR to accurately determine the molar ratio and then introducing it into the chromatographic system. This method uses the RMS determined by combining qNMR and chromatography instead of the analyte's reference material to determine its content in sample. This method has been adopted in the Japanese Pharmacopoeia, and the development of a general rule in the Japanese Agricultural Standards (JAS) is also under consideration.


Asunto(s)
Aditivos Alimentarios , Espectroscopía de Resonancia Magnética/métodos , Estándares de Referencia , Cromatografía Líquida de Alta Presión , Japón
18.
Cancers (Basel) ; 16(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38473359

RESUMEN

The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results.

19.
Front Neurol ; 15: 1354431, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38426169

RESUMEN

Background: The assessment of serum neurofilament light chain (sNFL) has emerged as a diagnostic and prognostic tool in monitoring multiple sclerosis (MS). However, the application of periodic measurement in daily practice remains unclear. Objective: To evaluate the predictive value of individual sNFL levels in determining disease activity in patients with relapsing MS (RMS). Methods: In this two-year prospective study, 129 RMS patients underwent quarterly sNFL assessments and annual MRI scans. The study analyzed the correlation between individual NFL levels and past, current, and future disease activity. Group-level Z-scores were employed as a comparative measure. Results: Among the 37 participants, a total of 61 episodes of disease activity were observed. sNFL levels proved valuable in distinct ways; they were confirmatory of previous and current clinical and/or radiological activity and demonstrated a high negative predictive value for future 90 days activity. Interestingly, Z-scores marginally outperformed sNFL levels in terms of predictive accuracy, indicating the potential for alternative approaches in disease activity assessment. In our cohort, sNFL cut-offs of 10.8 pg./mL (sensitivity 27%, specificity 90%) and 14.3 pg./mL (sensitivity 15%, specificity 95%) correctly identified 7 and 4 out of 26 cases of radiological activity within 90 days, respectively, with 14 and 15% false negatives. When using lower cut-off values, individuals with sNFL levels below 5 pg/mL (with a sensitivity of 92%, specificity of 25%, and negative predictive value of 94%) were less likely to experience radiological activity within the next 3 months. Conclusion: Individual sNFL levels may potentially confirm prior or current disease activity and predict short-term future radiological activity in RMS. These findings underscore its periodic measurement as a valuable tool in RMS management and decision-making, enhancing the precision of clinical evaluation in routine practice.

20.
Cureus ; 16(2): e54341, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38500901

RESUMEN

Background and objective Rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor characterized by skeletal muscle differentiation. While it is a common soft tissue sarcoma in children, its incidence significantly decreases with advancing age, rendering it exceptionally rare in individuals aged more than 45 years. This study aimed to shed light on the clinicopathological diversity and subtypes of RMS, thereby providing a comprehensive overview for enabling diagnostic precision and therapeutic strategies in treating this infrequently encountered malignancy in adults. Methodology This was a hospital-based cross-sectional study conducted in the Department of Pathology. Patients who were diagnosed with RMS over a period of three years were included in the study. The demographic features such as age and sex and aspects related to the tumor site, size, subtypes of RMS, and immunohistochemical expression were studied. Results A total of 14 cases were included in our study. The age at diagnosis ranged from four months to 65 years with a male-to-female ratio of 1:2.5. The sites of presentation were head and neck, trunk, pelvis, genitourinary tract, and retroperitoneum. The histological types were embryonal, alveolar, pleomorphic, and mixed and spindle cell types. The tumor cells were positive for immunohistochemistry markers desmin, MyoD1, and vimentin. Conclusion This study delved into the clinicopathological intricacies of RMS, offering comprehensive insights into its diverse subtypes. Our findings underscore the unique presentation of RMS in adults, with trunk and genitourinary tracts emerging as primary sites and alveolar and pleomorphic RMS observed as the predominant histological subtypes. Furthermore, the study sheds light on rare subtypes with distinct anatomical distributions.

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