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OBJECTIVE: This biomechanical pre-clinical study aimed to assess the consequences on mechanical properties of long term cold storage (+2 to +8 °C) of arterial allografts. METHODS: Femoropopliteal arterial segments were collected from multiorgan donors and stored at +2 to +8 °C for twelve months in saline solution with added antibiotics. Mechanical characterisation was carried out using two different tests, with the aim of defining the physiological modulus and the maximum stress and strain borne by the sample before rupture. These characterisations were carried out after zero, six, and twelve months of storage for each sample (T0, T6, and T12, respectively). For comparison, the same tests were performed on cryopreserved femoropopliteal segments after thawing. RESULTS: Twelve refrigerated allografts (RAs), each divided into three segments, and 10 cryopreserved allografts (CAs) were characterised. The median (interquartile range [IQR]) Young's modulus was not statistically significantly different between the storage times for cold stored allografts: RAT0, 164 (150, 188) kPa; RAT6, 178 (141, 185) kPa; RAT12, 177 (149, 185) kPa. The median (IQR) Young's modulus of the CA group (153; 130, 170 kPa) showed no significant differences from the RA groups, irrespective of storage time. Furthermore, median (IQR) maximum stress and strain values were not significantly different between the different groups: for maximum stress: RAT0, 1.58 (1.08, 2.09) MPa; RAT6, 1.74 (1.55, 2.36) MPa; RAT12, 2.25 (1.87, 2.53) MPa; CA, 2.25 (1.77, 2.61) MPa; and for maximum strain: RAT0, 64% (50, 90); RAT6, 79% (63, 84); RAT12, 72% (65, 86); CA, 67% (50, 95). CONCLUSION: Cold storage for up to twelve months appears to have no impact on the mechanical characteristics of human arterial allografts. Therefore, this preservation method, which would greatly simplify routine care, seems feasible. Other indicators are being studied to verify the safety of this preservation process before considering its use in vivo.
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In India, ginger is highly valued for cultural and medicinal purposes. Besides traditional uses, ginger has been proven for its efficacy in cancer, chemotherapy-induced nausea, bacterial infections, neuroinflammation, and oxidative stress. This study focuses on Zingiber sianginensis, a rare ginger species in the Siang region of Arunachal Pradesh, India. This study studied pharmacognostical evaluation, phytometabolomics analysis, and its effect on oxidative stress biomarkers. Microscopic and chemical tests were employed for pharmacognostical evaluation, revealing distinctive characteristics of Zingiber sianginensis, such as non-close collateral vascular bundles and unique cork layers. Chemical tests, including the phloroglucinol and hydrochloric acid test, differentiated Zingiber sianginensis from Zingiber officinale Roscoe. Phytometabolomics analysis, using Gas Chromatography-Mass Spectrometry (GC/MS) and Liquid Chromatography-Electrospray Ionisation-Quadrupole Time of Flight-Mass Spectrometry (LC-ESI-QTOF-MS/MS) techniques, identified a diverse range of metabolites in Zingiber sianginensis, including polyphenols, monoterpenoids, diterpenoids, sesquiterpenoids, and organic compounds. The LC-ESI-QTOF-MS/MS analysis revealed 158 compounds, verified through cross-referencing with established databases. Heavy metal analysis by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) confirmed that Zingiber sianginensis complies with safety standards, showing concentrations of heavy metals within acceptable limits. The isolation and characterization of compounds from Zingiber sianginensis identified natural products such as (R)-(-)- alpha-Curcumene (1), 1-Dehydro-[10]-gingerdione (2), 6-Shogaol (3), and 6-Gingerol (4). Quantification of 6-gingerol revealed that Zingiber sianginensis contains approximately twice the amount compared to Zingiber officinale Roscoe's, suggesting its potential as a source for higher 6-gingerol content. The hydroalcoholic extract of Zingiber sianginensis exhibited antioxidant properties, reducing oxidative stress biomarkers in human dermal fibroblast cells treated with rotenone. Allantoin and 3-bromotyrosine levels significantly decreased, indicating the extract's potential in combating oxidative stress-related disorders. Overall, this comprehensive study provides valuable insights into the pharmacognostical, phytometabolomic, and safety aspects of Zingiber sianginensis, highlighting its potential as a source of bioactive compounds with health benefits.
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Biomarcadores , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Estresse Oxidativo , Extratos Vegetais , Espectrometria de Massas em Tandem , Zingiber officinale , Biomarcadores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Metabolômica/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Zingiber officinale/química , Índia , Zingiberaceae/química , Antioxidantes/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Humanos , Cromatografia Líquida/métodosRESUMO
Plant peptidase inhibitors play crucial roles in plant defence mechanisms and physiological processes. In this study, we isolated and characterised a Kunitz trypsin inhibitor from Enterolobium gummiferum seeds named EgPI (E. gummiferum peptidase inhibitor). The purification process involved two chromatography steps using size exclusion and hydrophobic resins, resulting in high purity and yield. EgPI appeared as a single band of ~20 kDa in SDS-PAGE. Under reducing conditions, the inhibitor exhibited two polypeptide chains, with 15 and 5 kDa. Functional characterisation revealed that EgPI displayed an inhibition stoichiometry of 1:1 against trypsin, with a dissociation constant of 8.4 × 10-9 mol·L-1. The amino-terminal sequencing of EgPI revealed the homology with Kunitz inhibitors. Circular dichroism analysis provided insights into the secondary structure of EgPI, which displayed the signature typical of Kunitz inhibitors. Stability studies demonstrated that EgPI maintained the secondary structure necessary to exhibit its inhibitory activity up to 70 °C and over a pH range from 2 to 8. Microbiological screening revealed that EgPI has antibiofilm properties against pathogenic yeasts at 1.125 µmol·L-1, and EgPI reduced C. albicans biofilm formation by 82.7%. The high affinity of EgPI for trypsin suggests potential applications in various fields. Furthermore, its antibiofilm properties recommended its usefulness in agriculture and antimicrobial therapy research, highlighting the practical implications of our research.
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Biofilmes , Fabaceae , Proteínas de Plantas , Sementes , Inibidores da Tripsina , Sementes/química , Biofilmes/efeitos dos fármacos , Fabaceae/química , Inibidores da Tripsina/farmacologia , Inibidores da Tripsina/química , Inibidores da Tripsina/isolamento & purificação , Proteínas de Plantas/farmacologia , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Sequência de Aminoácidos , PeptídeosRESUMO
Lymphoedema tissue is characterised by excess free fluid and structural changes to the extracellular matrix (ECM) in the form of fibrotic and fatty deposition. These tissue characteristics are integral to the assessment of lymphoedema progression; however, clinicians and researchers often focus on changes in the free fluid, volume and function of lymphatic vasculature to inform practice. Subsequently, little is known about the effect of clinical interventions on lymphoedema tissue composition. This article presents a novel approach to classify lymphoedema tissue. The Localised Objective Characterisation Assessment of Lymphoedema (LOCAL) classification combines diagnostic and clinically meaningful objective assessment thresholds to infer lymphoedema pathophysiological changes in tissue layers. The LOCAL classification method was verified using data from fifteen women with unilateral breast cancer-related lymphoedema who were evaluated at three sites on each arm using high-frequency ultrasound (HFUS), bio-electrical impedance spectroscopy (BIS) and volume measurements. Participants exhibited an uneven distribution of volume between the proximal and distal segments of the arm (p = 0.023), with multiple tissue compositional categories observed across sites on the same limb (p < 0.001). The LOCAL method demonstrated utility in categorising a diverse range of lymphoedema tissue layer changes beyond what can be ascertained from whole-limb measures.
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Solidago canadensis L. (Canadian goldenrod) is a widely distributed invasive herb from the Asteraceae family. It contains compounds that can change the soil structure and its nutritional components and thus affect indigenous species' growth, germination, and survival. Consequently, it can pose a major ecological threat to biodiversity. On the other hand, many studies show that this species, due to its chemical properties, can be used for many positive purposes in pharmacy, agriculture, medicine, cosmetic industry, etc. S. canadensis contains a diverse array of bioactive compounds that may be responsible for antioxidant, antimicrobial, and anticancer activities. Many studies have discussed the invasiveness of S. canadensis, and several chemical and genetic differences between this plant in native and introduced environments have been discovered. Previous ecological and environmental evaluations of the potential of S. canadensis as an ecosystem services provider have come out with four promising groups of its products: active extracts, essential oil, fuel, and others. Although identified, there is a need for detailed validation and prioritisation of ecosystem services. This article aims to overview the S. canadensis invasive features, emphasising chemical characterisation and its potential for providing ecosystem services. Moreover, it identifies scenarios and proposes a methodology for estimating S. canadensis use in bioeconomy.
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OBJECTIVES: To assess the influence of peak tube voltage peak setting on adrenal adenomas (AA) attenuation on unenhanced abdominal CT. MATERIALS AND METHODS: IRB-approved retrospective observational cohort study. We included 89 patients with imaging-defined AAs with shortest diameter > 6 mm who underwent two or more unenhanced abdominal CTs using at least two different peak tube voltage settings. Two readers independently measured adenoma attenuation on different CT acquisitions by drawing a round ROI on 3 mm thick axial MPR reconstructions encompassing at least 2/3 of the lesion's surface. The mean of the values measured by the two readers was used for further analysis. Interobserver variability was assessed (Intraclass Correlation Coefficient). Attenuation values measured on 100, 110 and 140 kVp acquisitions were compared with standard 120 kVp ones (Bland-Altman analysis). RESULTS: We included 275 unenhanced abdominal CTs (3.1 ± 0.9/patient) in image analysis; 131 acquired at 120 kVp, 65 at 100 kVp, 59 at 110 kVp, and 20 at 140 kVp. 107 lesions were detected in 89 patients (1-4/patient), with a mean maximum diameter of 17 ± 6 mm. Interobserver agreement in attenuation measurement was excellent (ICC: 0.95, CI (92-97)). Median adenoma attenuation was significantly lower on 100 kVp images than on 120 kVp ones (-1 HU, IQR (-5 to 3.6), vs, 2.5 HU, IQR (-1.5 to 8.5); p < 0.001) whereas we didn't find statistically significant differences in adenoma attenuation between 110 kVp or 140 kVp and 120 kVp ones. CONCLUSION: AA attenuation is significantly lower on unenhanced CT scans acquired at 100 kVp than on those acquired at "standard" 120 kVp. CLINICAL RELEVANCE STATEMENT: AA attenuation is significantly lower at 100 kVp in comparison to 120 kVp. This might be exploited to increase unenhanced CT sensitivity in adenoma characterisation, but further studies including non-adenoma lesions are mandatory to confirm this hypothesis. KEY POINTS: CT scans are often acquired using peak tube voltage settings different from the "standard" 120 kVp. AA attenuation varies if CT scans are acquired using different tube peak voltage settings. At 100 kVp AAs show a significantly lower attenuation than at 120 kVp.
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RSA-1 is a polysaccharide obtained from Raphani semen with a relatively clear structure and anti-colon cancer activity. In this study, high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy were applied to characterise the complex chain structure of RSA-1. Subsequently, the inhibitory effect on colon cancer growth through apoptosis induction in colon cancer cells was explored. The findings indicate that the main chain of RSA-1 consists of â3)-ß-D-Galp-(1 â and 3,6)-ß-D-Galp-(1 â substituted at C-6 with branched α-L-Araf side chains. RSA-1 disrupts the Bax/Bcl-2 ratio and thus inhibits the viability of colon cancer cells in vitro. Furthermore, it inhibits colon cancer migration by attenuating epithelial-mesenchymal transition. Notably, RSA-1 exhibited negligible impact on the growth of human intestinal epithelial cells within a relevant concentration range. This study establishes a theoretical foundation and provides technical support for the prospective development and application of RSA-1 as a dual-purpose anti-colon cancer drug and functional food.
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Neoplasias do Colo , Galactanos , Humanos , Galactanos/química , Galactanos/farmacologia , Galactanos/isolamento & purificação , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacosRESUMO
Dynamic soft tissue characterisation is an important element in robotic minimally invasive surgery. This paper presents a novel method by combining neural network with recursive least square (RLS) estimation for dynamic soft tissue characterisation based on the nonlinear Hunt-Crossley (HC) model. It develops a radial basis function neural network (RBFNN) to compensate for the error caused by natural logarithmic factorisation (NLF) of the HC model for dynamic RLS estimation of soft tissue properties. The RBFNN weights are estimated according to the maximum likelihood principle to evaluate the probability distribution of the neural network modelling residual. Further, by using the linearisation error modelled by RBFNN to compensate for the linearised HC model, an RBFNN-based RLS algorithm is developed for dynamic soft tissue characterisation. Simulation and experimental results demonstrate that the proposed method can effectively model the natural logarithmic linearisation error, leading to improved accuracy for RLS estimation of the HC model parameters.
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Redes Neurais de Computação , Fatores de Tempo , Análise dos Mínimos Quadrados , Algoritmos , TatoRESUMO
In this study, a p-Si/ALD-Al2O3/Ti/Pt MOS (metal oxide semiconductor) device has been fabricated and used as a hydrogen sensor. The use of such a stack enables a reliable, industry-compatible CMOS fabrication process. ALD-Al2O3 has been chosen as it can be integrated into the back end of the line (BEOL) or in CMOS, post processing. The device response and recovery are demonstrated with good correlation between the capacitance variation and the hydrogen concentration. Detection down to 20 ppm at 140 °C was obtained and a response time of 56 s for 500 ppm was recorded.
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This study reports the presence, concentration, and characteristics of microplastics (MPs) in tap water in three suburbs in Gauteng Province in South Africa. Physical characterisation was conducted using stereomicroscopy and scanning electron microscopy following staining of MPs with the Rose Bengal dye. The concentrations of MPs in all samples ranged from 4.7 to 31 particles/L, with a mean of 14 ± 5.6 particles/L. Small-sized (<1 mm) and fibrous-shaped MPs were most abundant in all samples. Fibers accounted for 83.1% of MPs in samples from all the three areas, followed by fragments (12.4%), pellets/beads (3.1%), and films (1.5%), with a minor variation in the distribution of shapes and sizes in samples from each area. Raman microspectroscopy was used for chemical analysis, and five polymers were identified, namely: high-density polyethylene, polyurethane, polyethylene terephthalate, poly(hexamethylene terephtalamide), and poly(acrylamide-co-acrylic acid). C.I Pigment Red 1, C.I. Solvent Yellow 4, Potassium indigotetrasulphonate, and C.I Pigment Black 7 were the colourants detected. These colourants are carcinogenic and mutagenic and are potentially toxic to humans. The prevalence of MPs in tap water implies their inadequate removal during water treatment. For instance, the presence of poly(AM-co-AA) suggests that drinking water treatment plants may be a potential source of MPs in tap water. Other polymers, e.g., high-density polyethylene may be released from pipes during the transportation of drinking water. The estimated daily consumption of MPs from tap water was 1.2, 0.71, and 0.50 particles/kg.day for children, men, and women, respectively. The findings of this study provide evidence of the presence of MPs in drinking water in South Africa, thus giving some insights into the performance of treatment plants in removing these contaminants and a benchmark for the formulation of standard limits for the amount of MPs in drinking water.
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Água Potável , Monitoramento Ambiental , Microplásticos , Poluentes Químicos da Água , África do Sul , Microplásticos/análise , Poluentes Químicos da Água/análise , Água Potável/química , Plásticos/análiseRESUMO
The clinical management of metastatic urothelial carcinoma (mUC) is undergoing a major paradigm shift; the integration of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) into the mUC therapeutic strategy has succeeded in improving platinum-based chemotherapy outcomes. Given the expanding therapeutic armamentarium, it is crucial to identify efficacy-predictive biomarkers that can guide an individual patient's therapeutic strategy. We reviewed the literature data on mUC genomic alterations of clinical interest, discussing their prognostic and predictive role. In particular, we explored the role of the fibroblast growth factor receptor (FGFR) family, epidermal growth factor receptor 2 (HER2), mechanistic target of rapamycin (mTOR) axis, DNA repair genes, and microsatellite instability. Currently, based on the available clinical data, FGFR inhibitors and HER2-directed ADCs are effective therapeutic options for later lines of biomarker-driven mUC. However, emerging genomic data highlight the opportunity for earlier use and/or combination with other drugs of both FGFR inhibitors and HER2-directed ADCs and also reveal additional potential drug targets that could change mUC management.
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Receptor ErbB-2 , Humanos , Receptor ErbB-2/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundário , Genômica/métodos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Biomarcadores Tumorais/genética , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Instabilidade de MicrossatélitesRESUMO
The use of extracellular vesicles (EVs) generated by mesenchymal stem cells (MSCs) holds great promise as a novel therapeutic approach. Although their immunomodulatory and regeneration potential has been reported to be similar to that of MSCs, the use of MSC-derived EVs in clinical settings will require several problems to be resolved. It is necessary to develop a standardised and widely accepted isolation technology and to improve methods such as the quantification and characterisation of MSC-derived EVs. In this way, EV studies can be compared, the acquired knowledge can be safely transferred to clinical platforms and the clinical results can be evaluated appropriately. There are many procedures for the collection and analysis of vesicles derived from different cells; however, this review provides an overview of methods for the determination of the total protein amount, specific proteins, particle number, non-protein markers like lipids and RNA, microscopy and other methods focusing on MSC-derived EVs.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , RNA/metabolismo , ImunomodulaçãoRESUMO
This study analysed the probabilistic risk to consumers associated with the presence of iAs, Cd, Cr, Hg, Pb, acrylamide (AA) and ochratoxin A (OTA) in instant coffee from Brazil, Colombia, Mexico and Peru. The results found iAs to be the metal with the highest concentrations (3.50 × 10-2 to 6.00 × 10-2 mg/kg), closely followed by Pb (1.70 × 10-2 to 2.70 × 10-2 mg/kg) and Cr (5.00 × 10-3 to 1.00 × 10-2 mg/kg), although these differences were not significant between countries. Cd and Hg were not detected. Focusing on AA, the concentrations ranged from 1.77 × 10-1 mg/kg (Peru) to 4.77 × 10-1 mg/kg (Brazil), while OTA ranged from 1.32 × 10-3 (Peru) to 1.77 × 10-3 mg/kg (Brazil) with significant differences between countries in both cases. As regards risk, the hazard quotient and hazard index were less than 1, meaning that the consumption of instant coffee represents a low level of concern for non-genotoxic effects. The results of the combination of margin of exposure and probability of exceedance indicated that the non-genotoxic effects of Pb, AA and OTA pose no threat. However, the probability values of suffering cancer from iAs and AA (between 1 × 10-6 and 1 × 10-4) indicated a moderate risk and that management measures should be taken.
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Copper and copper oxide nanoparticles (CuNPs) have unique physicochemical properties that make them highly promising for biomedical applications. This review discusses the application of CuNPs in biomedicine, including diagnosis, therapy, and theranostics. Recent synthesis methods, with an emphasis on green approaches, are described, and the latest techniques for nanoparticle characterization are critically analyzed. CuNPs, including Cu2O, CuO, and Cu, have significant potential as anti-cancer agents, drug delivery systems, and photodynamic therapy enhancers, among other applications. While challenges such as ensuring biocompatibility and stability must be addressed, the state-of-the-art research reviewed here provides strong evidence for the efficacy and versatility of CuNPs. These multifunctional properties have been extensively researched and documented, showcasing the immense potential of CuNPs in biomedicine. Overall, the evidence suggests that CuNPs are a promising avenue for future research and development in biomedicine. We strongly support further progress in the development of synthesis and application strategies to enhance the effectiveness and safety of CuNPs for clinical purposes.
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Nanopartículas Metálicas , Nanopartículas , Cobre/química , Nanopartículas Metálicas/química , Nanopartículas/química , Antioxidantes/química , Extratos Vegetais/químicaRESUMO
Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.
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Estesioneuroblastoma Olfatório , Cavidade Nasal , Neoplasias Nasais , Humanos , Estesioneuroblastoma Olfatório/patologia , Estesioneuroblastoma Olfatório/terapia , Estesioneuroblastoma Olfatório/diagnóstico , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Neoplasias Nasais/diagnóstico , Cavidade Nasal/patologia , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: The physical characterisation of FFF-beam profiles in the presence of a magnetic field requires a new standardization procedure and formulation. PURPOSE: The aim of this multicentric experience is to propose new normalisation factors to allow for the calculation of standard parameters typical of flattened beams, such as dosimetric field size and penumbra, for a 6 MV FFF beam from an MR-linac. METHODS: The measurements were carried out on three ViewRay-MRIdiansystems. An equal set of measurements was acquired using the same equipment. Transverse beam profiles were acquired at seven different depthsand for six beam dimensions.The inflection point was estimated as the position of the maximum of a Gaussian fit obtained from the first derivative of the profiles. The position of the minimum and maximum points of the second derivative of the above Gaussian described the fall-off region, and the external peaks of the third derivative were considered as the in-field and out-field points. The profile normalisation was determined by imposing a 55% dose level at the inflection point and the renormalisation factors were calculated. RESULTS: The position of the inflection point, and the second and third derivatives peaks were analysed,and the renormalisation factors as a function of field size and depth were determined. The values of the unflatness and the slope have been calculated for different depths and field sizes. CONCLUSION: This study represents the first multi-centric evaluation of the profiles on different low-field MR-Linac systems and theset of renormalisation parameters to analyse the FFF-beam on that system was effectively proposed.
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Aceleradores de Partículas , Radiometria , Padrões de Referência , Dosagem RadioterapêuticaRESUMO
Fifty-seven Gallid alphaherpesvirus 2 (GaHV-2) isolates, collected during a 30-year period (1990-2019) from commercial poultry flocks affected by Marek's disease (MD), were molecularly characterised. The GaHV-2 meq gene was amplified and sequenced to evaluate the virus virulence, based on the number of PPPPs within the proline-rich repeats (PRRs) of its transactivation domain. The present illustration of virus virulence evaluation on a large scale of field virus isolates by molecular analysis exemplifies the practical benefit and usefulness of the molecular marker in commercial GaVH-2 isolates. The alternative assay of GaVH-2 virulence pathotyping is the classical Gold Standard ADOL method, which is difficult and impossible to employ on a large scale using the Specific Pathogen Free (SPF) chicks of the ADOL strains kept in isolators for two months. The phylogenetic analysis performed in the present study showed that the meq gene amino acid sequences of the 57 Israeli strains divide into 16 phylogenetic branches. The virulence evaluation was performed in comparison with 36 GaHV-2 prototype strains, previously characterised by the in vivo Gold Standard ADOL assay. The results obtained revealed that the GaHV-2 strains circulating in Israel have evolved into a higher virulence potential during the years, as the four-proline stretches number in the meq gene decreased over the investigated period, typically of very virulent virus prototypes. The present study supports the meq gene molecular markers for the assessment of field GaVH-2 strains virulence.
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Herpesvirus Galináceo 2 , Doença de Marek , Proteínas Oncogênicas Virais , Doenças das Aves Domésticas , Animais , Aves Domésticas , Israel , Virulência/genética , Filogenia , Proteínas Oncogênicas Virais/genética , Herpesvirus Galináceo 2/genética , Galinhas , Prolina/genéticaRESUMO
Caesalpinia bonducella L. is a traditional medicinal plant containing a potential homoisoflavonoid, bonducellin, with therapeutic values against polycystic ovary syndrome, oxidative damage, pathogenic bacteria, irregular menstrual cycle, ovarian cancer and diabetes. Owing to the multi-therapeutic properties of bonducellin, knowledge of its biosynthetic pathway genes will help understand its regulatory mechanism and thus improve the yield. This study sequenced C. bonducella seed mRNA transcriptome to identify the genes in bonducellin biosynthesis. Before this, the presence of bonducellin in the seed samples was analysed by HPLC using the chemically synthesised bonducellin as the standard. Seven key genes encoding enzymes involved in the synthesis of bonducellin via the phenylpropanoid pathway were identified. The expression of selective genes from the bonducellin biosynthetic pathway was validated using qRT-PCR and comparable with RNA-Seq data. Here, we put forth the sequences of 67,560 genes from C. bonducella and highlight the bonducellin biosynthetic pathway genes.
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Immune checkpoint therapies have significantly advanced cancer treatment. Nevertheless, the high costs and potential adverse effects associated with these therapies highlight the need for better predictive biomarkers to identify patients who are most likely to benefit from treatment. Unfortunately, the existing biomarkers are insufficient to identify such patients. New high-dimensional spatial technologies have emerged as a valuable tool for discovering novel biomarkers by analysing multiple protein markers at a single-cell resolution in tissue samples. These technologies provide a more comprehensive map of tissue composition, cell functionality, and interactions between different cell types in the tumour microenvironment. In this review, we provide an overview of how spatial protein-based multiplexing technologies have fuelled biomarker discovery and advanced the field of immunotherapy. In particular, we will focus on how these technologies contributed to (i) characterise the tumour microenvironment, (ii) understand the role of tumour heterogeneity, (iii) study the interplay of the immune microenvironment and tumour progression, (iv) discover biomarkers for immune checkpoint therapies (v) suggest novel therapeutic strategies.
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Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/tratamento farmacológico , Biomarcadores , Imunoterapia/métodos , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Tumorais/metabolismoRESUMO
Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022-2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four randomly selected samples underwent whole-genome sequencing. Analysis revealed a prevalent recombinant strain, merging type 3 and type 7 of human mastadenovirus B1 (HAd-B1) species, indicating the emergence of recent strains of species B in India. Furthermore, distinctions in VA-RNAs and the E3 region suggested that current circulating strains of human mastadenovirus B1 (HAd-B1) possess the capacity to evade host immunity, endure longer within hosts, and cause severe respiratory infections. This study underscores the significance of evaluating the complete genome sequence of HAdV isolates to glean insights into their outbreak potential and the severity of associated illnesses.