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1.
Proc Natl Acad Sci U S A ; 121(35): e2402435121, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39159372

RESUMEN

Firmly anchored on observational data, giant radio lobes from massive galaxies hosting supermassive black holes can exert a major negative feedback effect, by endowing the intergalactic gas with significant magnetic pressure hence retarding or preventing gas accretion onto less massive halos in the vicinity. Since massive galaxies that are largely responsible for producing the giant radio lobes, this effect is expected to be stronger in more overdense large-scale environments, such as protoclusters, than in underdense regions, such as voids. We show that by redshift [Formula: see text] halos with masses up to [Formula: see text] are significantly hindered from accreting gas due to this effect for radio bubble volume filling fraction of [Formula: see text], respectively. Since the vast majority of the stars in the universe at [Formula: see text][Formula: see text] 2 to 3 form precisely in those halos, this negative feedback process is likely one major culprit for causing the global downturn in star formation in the universe. It also provides a natural explanation for the rather sudden flattening of the slope of the galaxy rest-frame UV luminosity function around [Formula: see text]. A cross-correlation between protoclusters and Faraday rotation measures may test the predicted magnetic field. Inclusion of this external feedback process in the next generation of cosmological simulations may be imperative.

2.
Annu Rev Phys Chem ; 75(1): 307-327, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38382568

RESUMEN

The discovery of more than 200 gas-phase chemical compounds in interstellar space has led to the speculation that this nonterrestrial synthesis may play a role in the origin of life. These identifications were possible because of laboratory spectroscopy, which provides the molecular fingerprints for astronomical observations. Interstellar chemistry produces a wide range of small, organic molecules in dense clouds, such as NH2COCH3, CH3OCH3, CH3COOCH3, and CH2(OH)CHO. Carbon (C) is also carried in the fullerenes C60 and C70, which can preserve C-C bonds from circumstellar environments for future synthesis. Elusive phosphorus has now been found in molecular clouds, the sites of star formation, in the molecules PO and PN. Such clouds can collapse into solar systems, although the chemical/physical processing of the emerging planetary disk is uncertain. The presence of molecule-rich interstellar starting material, as well as the link to planetary bodies such as meteorites and comets, suggests that astrochemical processes set a prebiotic foundation.

3.
Nano Lett ; 24(29): 8859-8865, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38981024

RESUMEN

Cryogenic temperatures are crucial for the operation of semiconductor quantum electronic devices, yet the heating effects induced by microwave or laser signals used for quantum state manipulation can lead to significant temperature variations at the nanoscale. Therefore, probing the temperature of individual devices in working conditions and understanding the thermodynamics are paramount for designing and operating large-scale quantum computing systems. In this study, we demonstrate high-sensitivity fast thermometry in a silicon nanotransistor at cryogenic temperatures using RF reflectometry. Through this method, we explore the thermodynamic processes of the nanotransistor during and after a laser pulse and determine the dominant heat dissipation channels in the few-kelvin temperature range. These insights are important to understand thermal budgets in quantum circuits, with our techniques being compatible with microwave and laser radiation, offering a versatile approach for studying other quantum electronic devices in working conditions.

4.
Expert Rev Mol Med ; 26: e14, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38623751

RESUMEN

Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.


Asunto(s)
Neoplasias del Recto , Humanos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Terapia Molecular Dirigida , Terapia Neoadyuvante/métodos , Terapia Combinada , Resultado del Tratamiento , Animales
5.
Magn Reson Med ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136249

RESUMEN

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.

6.
Ann Surg Oncol ; 31(7): 4189-4196, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38652200

RESUMEN

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].


Asunto(s)
Neoplasias Intestinales , Intestino Delgado , Tumores Neuroendocrinos , Octreótido , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Cirugía Asistida por Computador , Humanos , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/diagnóstico por imagen , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Neoplasias Intestinales/cirugía , Neoplasias Intestinales/patología , Neoplasias Intestinales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Intestino Delgado/patología , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/cirugía , Octreótido/análogos & derivados , Adulto , Cirugía Asistida por Computador/métodos , Compuestos Organometálicos , Somatostatina/análogos & derivados , Estudios de Seguimiento , Pronóstico , Partículas beta/uso terapéutico , Estudios de Factibilidad
7.
BMC Cancer ; 24(1): 459, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609887

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood. METHODS: Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements. RESULTS: Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11). CONCLUSIONS: Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.


Asunto(s)
Neoplasias de Cabeza y Cuello , Monocitos , Humanos , Antígeno B7-H1 , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Quimiocina CXCL11 , Neoplasias de Cabeza y Cuello/terapia , Microambiente Tumoral
8.
J Neurooncol ; 167(2): 233-241, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38372901

RESUMEN

BACKGROUND: Autopsy-based radio-pathomic maps of glioma pathology have shown substantial promise inidentifying areas of non-enhancing tumor presence, which may be able to differentiate subsets of patients that respond favorably to treatments such as bevacizumab that have shown mixed efficacy evidence. We tested the hypthesis that phenotypes of non-enhancing tumor fronts can distinguish between glioblastoma patients that will respond favorably to bevacizumab and will visually capture treatment response. METHODS: T1, T1C, FLAIR, and ADC images were used to generate radio-pathomic maps of tumor characteristics for 79 pre-treatment patients with a primary GBM or high-grade IDH1-mutant astrocytoma for this study. Novel phenotyping (hypercellular, hypocellular, hybrid, or well-circumscribed front) of the non-enhancing tumor front was performed on each case. Kaplan Meier analyses were then used to assess differences in survival and bevacizumab efficacy between phenotypes. Phenotype compartment segmentations generated longitudinally for a subset of 26 patients over the course of bevacizumab treatment, where a mixed effect model was used to detect longitudinal changes. RESULTS: Well-Circumscribed patients showed significant/trending increases in survival compared to Hypercellular Front (HR = 2.0, p = 0.05), Hypocellular Front (HR = 2.02, p = 0.03), and Hybrid Front tumors (HR = 1.75, p = 0.09). Only patients with hypocellular or hybrid fronts showed significant survival benefits from bevacizumab treatment (HR = 2.35, p = 0.02; and HR = 2.45, p = 0.03, respectively). Hypocellular volumes decreased by an average 50.52 mm3 per day of bevacizumab treatment (p = 0.002). CONCLUSION: Patients with a hypocellular tumor front identified by radio-pathomic maps showed improved treatment efficacy when treated with bevacizumab, and reducing hypocellular volumes over the course of treatment may indicate treatment response.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Humanos , Bevacizumab/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Recurrencia Local de Neoplasia/patología , Imagen por Resonancia Magnética/métodos
9.
Cancer Control ; 31: 10732748241274559, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39150275

RESUMEN

PURPOSE: Hepatic metastasis frequently occurs in patients who have undergone radical pancreatic resection for pancreatic cancer. Besides chemotherapy, various local treatment approaches targeting hepatic lesions have been explored. However, research on radiofrequency ablation (RFA) as a localized therapy for hepatic metastasis is limited. Therefore, we conducted this retrospective study to provide clinical evidence. METHODS: This is a single-center, retrospective, cohort study. After radical pancreaticoduodenectomy, 32 patients developed metachronous hepatic metastasis with fewer than 3 lesions, the largest of which was less than 3 cm in diameter. These patients underwent combined treatment with chemotherapy and RFA. After 8 weeks of chemotherapy, patients received RFA for hepatic lesions. Additional chemotherapy was administered, and the patients' tumor status and survival were monitored. The primary endpoint of this study was overall survival (OS). Factors affecting OS were analyzed using the Cox risk model. RESULTS: Among the 32 patients, the mean OS was 28.4 months. Univariate and multivariate Cox regression analysis revealed that the time (in months) of liver metastasis (HR = 0.04, 95% CI: 0.01 to 0.19; P < 0.001), the number of liver metastases (HR = 7.08, 95% CI: 1.85 to 27.08, P = 0.004), and PD (progressive disease) response to the second round of chemotherapy (HR = 29.50, 95% CI: 1.46 to 597.27; P = 0.027) were independent predictors of poorer survival. CONCLUSION: Combined therapy with RFA and chemotherapy is safe in patients with hepatic metastasis after radical pancreaticoduodenectomy. Early recurrence (≤12 months), three liver metastatic lesions, and a poor response to the second round of chemotherapy were associated with poor survival.


Asunto(s)
Neoplasias Hepáticas , Neoplasias Pancreáticas , Ablación por Radiofrecuencia , Humanos , Masculino , Femenino , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Persona de Mediana Edad , Estudios Retrospectivos , Ablación por Radiofrecuencia/métodos , Anciano , Terapia Combinada , Pancreaticoduodenectomía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto
10.
Pediatr Transplant ; 28(4): e14599, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38713752

RESUMEN

BACKGROUND: The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS: A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS: The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS: Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.


Asunto(s)
Densidad Ósea , Trasplante de Hígado , Donadores Vivos , Vértebras Torácicas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Vértebras Torácicas/cirugía , Vértebras Torácicas/diagnóstico por imagen , Lactante , Adulto Joven , Resultado del Tratamiento , Factores Sexuales
11.
Philos Trans A Math Phys Eng Sci ; 382(2271): 20230072, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38522462

RESUMEN

At redshifts beyond [Formula: see text], the 21 cm line from neutral hydrogen is expected to be essentially the only viable probe of the three-dimensional matter distribution. The lunar far-side is an extremely appealing site for future radio arrays that target this signal, as it is protected from terrestrial radio frequency interference, and has no ionosphere to attenuate and absorb radio emission at low frequencies (tens of MHz and below). We forecast the sensitivity of low-frequency lunar radio arrays to the bispectrum of the 21 cm brightness temperature field, which can in turn be used to probe primordial non-Gaussianity generated by particular early universe models. We account for the loss of particular regions of Fourier space due to instrumental limitations and systematic effects, and predict the sensitivity of different representative array designs to local-type non-Gaussianity in the bispectrum, parametrized by [Formula: see text]. Under the most optimistic assumption of sample variance-limited observations, we find that [Formula: see text] could be achieved for several broad redshift bins at [Formula: see text] if foregrounds can be removed effectively. These values degrade to between [Formula: see text] and 0.7 for [Formula: see text] to [Formula: see text], respectively, when a large foreground wedge region is excluded. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

12.
Philos Trans A Math Phys Eng Sci ; 382(2271): 20230068, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38522466

RESUMEN

The hydrogen 21-cm signal is predicted to be the richest probe of the young Universe, including those eras known as the cosmic Dark Ages, the Cosmic Dawn (when the first star and black hole formed) and the Epoch of Reionization. This signal holds the key to deciphering processes that take place at the early stages of cosmic history. In this opinion piece, we discuss the potential scientific merit of lunar observations of the 21-cm signal and their advantages over more affordable terrestrial efforts. The Moon is a prime location for radio cosmology which will enable precision observations of the low-frequency radio sky. The uniqueness of such observations is that they will provide an unparalleled opportunity to test cosmology and the nature of dark matter using the Dark Ages 21-cm signal. No less enticing is the opportunity to obtain a much clearer picture of the Cosmic Dawn than that currently achievable from the ground, which will allow us to determine the properties of the first stars and black holes. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

13.
Philos Trans A Math Phys Eng Sci ; 382(2271): 20230094, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38522461

RESUMEN

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

14.
Bioorg Chem ; 148: 107449, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759356

RESUMEN

Mitotic kinesin Eg5 isozyme as a motor protein plays a critical role in cell division of tumor cells. Kinesin Eg5 selective inhibitors and Colchicine binding site suppressors are essential targets for many anticancer drugs and radio chemotherapies. On this work, a new series of octahydroquinazoline as anti-mitotic candidates 2-13 has been synthesized with dual inhibition of tubulin polymerization/Eg5 against HCC cell line. All octahydroquinazolines have been in vitro assayed against HepG-2 cytotoxicity, Eg5 inhibitory and anti-tubulin polymerization activities. The most active analogues 7, 8, 9, 10, and 12 against HepG-2 were further subjected to in vitro cytotoxic assay against HCT-116 and MCF-7 cell lines. Chalcones 9, 10, and 12 displayed the most cytotoxic potency and anti-tubulin aggregation in comparable with reference standard colchicine and potential anti-mitotic Eg5 inhibitory activity in comparison with Monastrol as well. Besides, they exhibited cell cycle arrest at the G2/M phase. Moreover, good convinced apoptotic activities have been concluded as overexpression of caspase-3 levels and tumor suppressive gene p53 in parallel with higher induction of Bax and inhibition of Bcl-2 biomarkers. Octahydroquinazoline 10 displayed an increase in caspase-3 by 1.12 folds compared to standard colchicine and induce apoptosis and demonstrated cell cycle arrest in G2/M phase arrest by targeting p53 pathway. Analogue 10 has considerably promoted cytotoxic radiation activity and boosted apoptotic induction in HepG-2 cells by 1.5 fold higher than standard colchicine.


Asunto(s)
Antineoplásicos , Apoptosis , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Cinesinas , Polimerizacion , Quinazolinas , Moduladores de Tubulina , Tubulina (Proteína) , Humanos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Quinazolinas/farmacología , Quinazolinas/química , Quinazolinas/síntesis química , Tubulina (Proteína)/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Cinesinas/antagonistas & inhibidores , Cinesinas/metabolismo , Polimerizacion/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo
15.
Bioorg Chem ; 143: 107101, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38183682

RESUMEN

In part due to the resilience of cellular feedback pathways that develop therapeutic resistance to targeting the EGFR alone, using EGFR inhibitors alone was demonstrated to be unsuccessful in clinical trials. The over-activation of the signal transducer/activator of transcription 3 (STAT3) during the administration of an EGFR inhibitor is expected to play a substantial part in the failure and resistance of EGFR inhibitor treatment. Therein, we proposed a hypothesis that induced STAT3-mediated resistance to EGFR inhibition therapy could be addressed by a dual inhibition of EGFR and STAT3 method. To this end, we tried to discover new thieno[2,3-d]pyrimidine derivatives "5a-o". Results from the screening on A549 and MCF7 cancer cell lines revealed that compounds 5j and 5k showed two-digit nanomolar with appropriate safety towards the WI-38 cell line. The best molecules, 5j and 5k, were subjected to γ-radiation, and their cytotoxic efficacy didn't change after irradiation, demonstrating that not having to use it avoided its side effects. Compounds 5j and 5k demonstrated the highest inhibition when their potency was tested as dual inhibitors on EGFR 67 and 41 nM, respectively, and STAT3 5.52 and 3.34 nM, respectively, proved with in silico molecular docking and dynamic simulation. In light of the results presented above, the capacity of both powerful compounds to alter the cell cycle and initiate the apoptotic process in breast cancer MCF7 cells was investigated. Caspase-8, Bcl-2, Bax and Caspase-9 apoptotic indicators were studied.


Asunto(s)
Antineoplásicos , Receptores ErbB , Factor de Transcripción STAT3 , Humanos , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Estructura Molecular , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Relación Estructura-Actividad
16.
Environ Res ; 251(Pt 2): 118629, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38490626

RESUMEN

BACKGROUND: A knowledge gap exists regarding longitudinal assessment of personal radio-frequency electromagnetic field (RF-EMF) exposures globally. It is unclear how the change in telecommunication technology over the years translates to change in RF-EMF exposure. This study aims to evaluate longitudinal trends of micro-environmental personal RF-EMF exposures in Australia. METHODS: The study utilised baseline (2015-16) and follow-up (2022) data on personal RF-EMF exposure (88 MHz-6 GHz) measured across 18 micro-environments in Melbourne. Simultaneous quantile regression analysis was conducted to compare exposure data distribution percentiles, particularly median (P50), upper extreme value (P99) and overall exposure trends. RF-EMF exposures were compared across six exposure source types: mobile downlink, mobile uplink, broadcast, 5G-New Radio, Others and Total (of the aforementioned sources). Frequency-specific exposures measured at baseline and follow-up were compared. Total exposure across different groups of micro-environment types were also compared. RESULTS: For all micro-environmental data, total (median and P99) exposure levels did not significantly change at follow-up. Overall exposure trend of total exposure increased at follow-up. Mobile downlink contributed the highest exposure among all sources showing an increase in median exposure and overall exposure trend. Of seven micro-environment types, five of them showed total exposure levels (median and P99) and overall exposure trend increased at follow-up.


Asunto(s)
Campos Electromagnéticos , Exposición a Riesgos Ambientales , Ondas de Radio , Campos Electromagnéticos/efectos adversos , Ondas de Radio/efectos adversos , Humanos , Estudios Longitudinales , Victoria , Australia
17.
Environ Res ; 260: 119524, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972338

RESUMEN

This review offers a detailed examination of the current landscape of radio frequency (RF) electromagnetic field (EMF) assessment tools, ranging from spectrum analyzers and broadband field meters to area monitors and custom-built devices. The discussion encompasses both standardized and non-standardized measurement protocols, shedding light on the various methods employed in this domain. Furthermore, the review highlights the prevalent use of mobile apps for characterizing 5G NR radio network data. A growing need for low-cost measurement devices is observed, commonly referred to as "sensors" or "sensor nodes", that are capable of enduring diverse environmental conditions. These sensors play a crucial role in both microenvironmental surveys and individual exposures, enabling stationary, mobile, and personal exposure assessments based on body-worn sensors, across wider geographical areas. This review revealed a notable need for cost-effective and long-lasting sensors, whether for individual exposure assessments, mobile (vehicle-integrated) measurements, or incorporation into distributed sensor networks. However, there is a lack of comprehensive information on existing custom-developed RF-EMF measurement tools, especially in terms of measuring uncertainty. Additionally, there is a need for real-time, fast-sampling solutions to understand the highly irregular temporal variations EMF distribution in next-generation networks. Given the diversity of tools and methods, a comprehensive comparison is crucial to determine the necessary statistical tools for aggregating the available measurement data.

18.
Bioelectromagnetics ; 45(6): 281-292, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38778514

RESUMEN

Fifth generation (5G) wireless communication is being rolled out around the world. In this work, the latest radio frequency electromagnetic field (EMF) exposure measurement results on commercial 28-GHz band 5G base stations (BSs) deployed in the urban area of Tokyo, Japan, are presented. The measurements were conducted under realistic traffic conditions with a 5G smartphone and using both omnidirectional and horn antennas. First and foremost, in all cases, the electric-field (E-field) intensity is much lower (<-38 dB) than the exposure limits. The E-field intensities for traffic-off cases do not show any significant difference between the two antennas with the maximum being 3.6 dB. For traffic-on cases, the omnidirectional antenna can undesirably capture the radio wave from the smartphone in some cases, resulting in a 7-13 dB higher E-field intensity than that using the horn antenna. We also present comparative results between 4G long term evolution BSs and sub-6-GHz band and 28-GHz band 5G BSs and provide recommendations on acquiring meaningful EMF exposure data. This work is a further step toward the standardization of the measurement method regarding quasi-millimeter/millimeter wave 5G BSs.


Asunto(s)
Campos Electromagnéticos , Campos Electromagnéticos/efectos adversos , Tokio , Tecnología Inalámbrica , Monitoreo de Radiación/métodos , Monitoreo de Radiación/instrumentación , Ondas de Radio/efectos adversos , Exposición a Riesgos Ambientales/análisis , Teléfono Inteligente , Humanos , Japón
19.
World J Surg Oncol ; 22(1): 178, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971793

RESUMEN

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.


Asunto(s)
Axila , Neoplasias de la Mama , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Neoplasia Residual , Biopsia del Ganglio Linfático Centinela , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/diagnóstico por imagen , Escisión del Ganglio Linfático/métodos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Prospectivos , Adulto , Biopsia del Ganglio Linfático Centinela/métodos , Anciano , Neoplasia Residual/cirugía , Neoplasia Residual/patología , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Estudios de Seguimiento , Pronóstico , Metástasis Linfática , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Factibilidad
20.
IEEE Sens J ; 24(3): 3863-3873, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39131729

RESUMEN

Ultra high frequency (UHF) passive radio frequency identification (RFID) tag-based sensors are proposed for intravenous (IV) fluid level monitoring in medical Internet of Things (IoT) applications. Two versions of the sensor are proposed: a binary sensor (i.e., full vs. empty state sensing) and a real-time (i.e., continuous level) sensor. The operating principle is demonstrated using full-wave electromagnetic simulation at 910 MHz and validated with experimental results. Generalized Additive Model (GAM) and random forest algorithms are employed for each interrogation dataset. Real-time sensing is accomplished with small deviations across the models. A minimum of 72% and a maximum of 97% of cases are within a 20% error for the GAM model and 62% to 98% for the random forest model. The proposed sensor is battery-free, lightweight, low-cost, and highly reliable. The read range of the proposed sensor is 4.6 m.

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