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1.
Regul Toxicol Pharmacol ; 122: 104919, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33753112

RESUMEN

The Standard for Exchange of Nonclinical Data (SEND) has been adopted by the US FDA, which has required pharmaceutical companies who are developing new drugs for the US market to implement SEND. The Japan Pharmaceutical Manufacturers Association (JPMA) SEND Taskforce Team responded to this situation by starting a project to better understand the contents of SEND datasets. The project focused on domains generally included in the SEND domains for single- and repeat-dose general toxicology studies, and surveyed what kind of information are populated in which domains and in what way. The qualitative analysis of the results indicated that variations exist based on whether or not an individual variable was populated and on how the variable was populated. The Taskforce Team recommends reducing variations not only in the SEND datasets but also in the descriptions in the study protocol and/or final study report. Reduction of such variations should lead to higher quality datasets with powerful and increased searchability so that accumulated SEND datasets should become more valuable. These efforts would provide regulatory agencies with easier review of SEND datasets, which contributes to efficient development of new drug candidates.


Asunto(s)
Investigación Biomédica/normas , Bases de Datos como Asunto/normas , Industria Farmacéutica/normas , Investigación Biomédica/organización & administración , Drogas en Investigación/normas , Humanos , Japón , Estados Unidos , United States Food and Drug Administration/normas
2.
Int J Comput Assist Radiol Surg ; 19(4): 655-664, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38498132

RESUMEN

PURPOSE: Pancreatic duct dilation is associated with an increased risk of pancreatic cancer, the most lethal malignancy with the lowest 5-year relative survival rate. Automatic segmentation of the dilated pancreatic duct from contrast-enhanced CT scans would facilitate early diagnosis. However, pancreatic duct segmentation poses challenges due to its small anatomical structure and poor contrast in abdominal CT. In this work, we investigate an anatomical attention strategy to address this issue. METHODS: Our proposed anatomical attention strategy consists of two steps: pancreas localization and pancreatic duct segmentation. The coarse pancreatic mask segmentation is used to guide the fully convolutional networks (FCNs) to concentrate on the pancreas' anatomy and disregard unnecessary features. We further apply a multi-scale aggregation scheme to leverage the information from different scales. Moreover, we integrate the tubular structure enhancement as an additional input channel of FCN. RESULTS: We performed extensive experiments on 30 cases of contrast-enhanced abdominal CT volumes. To evaluate the pancreatic duct segmentation performance, we employed four measurements, including the Dice similarity coefficient (DSC), sensitivity, normalized surface distance, and 95 percentile Hausdorff distance. The average DSC achieves 55.7%, surpassing other pancreatic duct segmentation methods on single-phase CT scans only. CONCLUSIONS: We proposed an anatomical attention-based strategy for the dilated pancreatic duct segmentation. Our proposed strategy significantly outperforms earlier approaches. The attention mechanism helps to focus on the pancreas region, while the enhancement of the tubular structure enables FCNs to capture the vessel-like structure. The proposed technique might be applied to other tube-like structure segmentation tasks within targeted anatomies.


Asunto(s)
Abdomen , Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Páncreas , Tomografía Computarizada por Rayos X , Conductos Pancreáticos/diagnóstico por imagen
3.
Int J Comput Assist Radiol Surg ; 17(2): 343-354, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34951681

RESUMEN

PURPOSE: Pancreatic duct dilation can be considered an early sign of pancreatic ductal adenocarcinoma (PDAC). However, there is little existing research focused on dilated pancreatic duct segmentation as a potential screening tool for people without PDAC. Dilated pancreatic duct segmentation is difficult due to the lack of readily available labeled data and strong voxel imbalance between the pancreatic duct region and other regions. To overcome these challenges, we propose a two-step approach for dilated pancreatic duct segmentation from abdominal computed tomography (CT) volumes using fully convolutional networks (FCNs). METHODS: Our framework segments the pancreatic duct in a cascaded manner. The pancreatic duct occupies a tiny portion of abdominal CT volumes. Therefore, to concentrate on the pancreas regions, we use a public pancreas dataset to train an FCN to generate an ROI covering the pancreas and use a 3D U-Net-like FCN for coarse pancreas segmentation. To further improve the dilated pancreatic duct segmentation, we deploy a skip connection on each corresponding resolution level and an attention mechanism in the bottleneck layer. Moreover, we introduce a combined loss function based on Dice loss and Focal loss. Random data augmentation is adopted throughout the experiments to improve the generalizability of the model. RESULTS: We manually created a dilated pancreatic duct dataset with semi-automated annotation tools. Experimental results showed that our proposed framework is practical for dilated pancreatic duct segmentation. The average Dice score and sensitivity were 49.9% and 51.9%, respectively. These results show the potential of our approach as a clinical screening tool. CONCLUSIONS: We investigate an automated framework for dilated pancreatic duct segmentation. The cascade strategy effectively improved the segmentation performance of the pancreatic duct. Our modifications to the FCNs together with random data augmentation and the proposed combined loss function facilitate automated segmentation.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada por Rayos X , Abdomen , Humanos , Páncreas , Conductos Pancreáticos/diagnóstico por imagen
4.
IEEE Int Conf Rehabil Robot ; 2017: 1061-1066, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28813962

RESUMEN

Various studies have been conducted in the field of the development/deterioration of standing and walking ability. In standing and walking control strategy, the relationship linking visual/somatosensory/vestibular-system information and physical movement is important. Researchers have previously sought to evaluate attitude control based on human sensory information. The authors have also reported that the body sway of a walking infant is mitigated when the subject holds a helium-filled balloon, with results suggesting that this approach can be applied to extend walking distance. This study was conducted to clarify how holding a balloon influences standing control strategy. A novel system was developed to quantitatively monitor and evaluate the standing state of subjects holding such a balloon. The results of the experiments conducted indicate that attitude control strategy changes in response to somatosensory information provided by the physical connection with the balloon.


Asunto(s)
Equilibrio Postural/fisiología , Postura/fisiología , Análisis y Desempeño de Tareas , Adulto , Helio , Humanos , Masculino , Procesamiento de Señales Asistido por Computador/instrumentación , Adulto Joven
5.
Neurosci Lett ; 353(2): 131-4, 2003 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-14664918

RESUMEN

The mechanism of radiation-induced diffuse brain injury was investigated in a neonatal rat hemicranial irradiation model using immunohistochemistry. Neonatal Fischer 344 rats received hemicranial irradiation with a single dose of 15 Gy, and appropriate combinations of myelin markers were used to assess the myelin damage at various stages of myelin development. Antibodies against myelin basic protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin oligodendrocyte glycoprotein were used, and the density of the antibody-positive fibers was classified into five categories. Statistical analysis showed significant differences between irradiated and unirradiated hemispheres. The differences decreased and myelination approached normality by postnatal day 70. These results show that myelination in the neonatal rat can recover from the developmental delay caused by a single 15 Gy dose of hemicranial irradiation.


Asunto(s)
Encéfalo/efectos de la radiación , Vaina de Mielina/efectos de la radiación , 2',3'-Nucleótido Cíclico Fosfodiesterasas/metabolismo , Animales , Animales Recién Nacidos , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Lateralidad Funcional/efectos de la radiación , Inmunohistoquímica , Proteína Básica de Mielina/metabolismo , Proteínas de la Mielina , Vaina de Mielina/patología , Glicoproteína Asociada a Mielina/metabolismo , Glicoproteína Mielina-Oligodendrócito , Ratas , Ratas Endogámicas F344
6.
Nephron Exp Nephrol ; 95(2): e55-61, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14610324

RESUMEN

BACKGROUND: Available evidence has shown that endothelin-1 (ET-1) acts in an autocrine/paracrine fashion rather than as a hormone or cytokine. Therefore, the analysis of local ET-1 production is a crucial step toward understanding its physiological and pathophysiological importance. In this study, in situ RT-PCR was utilized to detect tubular expression of prepro-ET-1 mRNA in normal rat kidney. METHODS: Kidneys were taken from normal Sprague-Dawley rats weighing approximately 200 g. In situ RT-PCR was carried out using the preparations embedded in paraffin and cut at a thickness of 8 microm. Furthermore, we tried semiquantitation of the prepro-ET-1 mRNA expression along different nephron segments by densitometric analysis. RESULTS: Prepro-ET-1 mRNA expression was detected in all tubular segments of the kidney from normal rats. Densitometric analysis demonstrated its highest expression in cortical collecting duct (CCD) and outer medullary collecting duct (OMCD). The expression was the lowest in thin descending limb of Henle's loop (TDL). CONCLUSION: This study showed that all tubular segments have the ability to synthesize ET-1 in rat kidney. It would be worth evaluating the levels prepro-ET-1 mRNA expression in various diseases by in situ RT-PCR to understand its pathophysiological role in such settings.


Asunto(s)
Endotelina-1/metabolismo , Riñón/química , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Animales , Densitometría/métodos , Femenino , Túbulos Renales Colectores/química , Ratas , Ratas Sprague-Dawley
7.
Toxicol Appl Pharmacol ; 184(3): 165-71, 2002 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-12460744

RESUMEN

To elucidate the mechanisms responsible for the development of HgCl(2)-induced acute renal failure (ARF), we examined the expression of brain type (b) nitric oxide synthase (NOS), which is involved in the generation of the vasodilator nitric oxide (NO), in the renal cortex of rats at 20 h after exposure to 7.5 mg/kg HgCl(2). Both blood urea nitrogen and serum creatinine were significantly increased in rats exposed to HgCl(2) relative to control rats, indicating the induction of ARF resulting from HgCl(2) exposure. Histopathological analysis demonstrated that, in addition to necrosis of proximal tubule epithelial cells, necrosis of macula densa cells and swelling of glomerular epithelial cells were observed in the renal cortex of rats with HgCl(2)-induced ARF. Consequently, the number of pars maculata segments was decreased by 42% in rats with HgCl(2)-induced ARF compared to control rats. The primary sites of bNOS mRNA and protein expression were macula densa cells and glomerular epithelial cells in the renal cortex of control rats and rats with HgCl(2)-induced ARF. The abundance of the bNOS mRNA and protein was significantly decreased in rats with HgCl(2)-induced ARF relative to control rats. These observations suggest that the production of the vasodilator NO derived from bNOS is decreased at the glomerulus level in the HgCl(2)-induced ARF setting. Thus, the reduction in bNOS expression may in part contribute to the progression of HgCl(2)-induced ARF through the deterioration of glomerular hemodynamics. In addition, the decrease in bNOS expression may be primarily the result of cell injury caused by the cytotoxic effect of HgCl(2).


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Glomérulos Renales/efectos de los fármacos , Cloruro de Mercurio/toxicidad , Óxido Nítrico Sintasa/biosíntesis , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/patología , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Células Epiteliales/patología , Femenino , Inmunohistoquímica , Hibridación in Situ , Glomérulos Renales/enzimología , Glomérulos Renales/patología , Necrosis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo I , Proteínas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
Neuropathology ; 23(4): 301-6, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14719546

RESUMEN

In the present study, an unusual example of malformation in a 9-day-old-girl, in whom an extracerebral ectopic mass with cysts was found in the anterior cranial cavity, is reported. The brain proper was well developed. The mass was connected to the cerebral base and consisted of neuroglial tissue showing various characteristics of differentiation, including cerebellar cortex and monoaminergic neurons. The ectopia may have developed from the mediobasal portion of the embryonic telencephalon.


Asunto(s)
Coristoma/patología , Quistes/patología , Malformaciones del Sistema Nervioso/patología , Cráneo , Niño , Femenino , Humanos
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