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Sexually transmitted diseases are major causes of infertility, ectopic pregnancy, and premature birth. Here, we developed a new multiplex real-time polymerase chain reaction (PCR) assay for the simultaneous detection of nine major sexually transmitted infections (STIs) found in Vietnamese women, including Chlamydia trachomatis, Neisseria gonorrhoeae, Gardnerella vaginalis, Trichomonas vaginalis, Candida albicans, Mycoplasma hominis, Mycoplasma genitalium, and human alphaherpesviruses 1 and 2. A panel containing three tubes × three pathogens/tube was predesigned based on double-quenched TaqMan probes to increase detection sensitivity. There was no cross-reactivity among the nine STIs and other non-targeted microorganisms. Depending on each pathogen, the agreement with commercial kits, sensitivity, specificity, repeatability and reproducibility coefficient of variation (CV), and limit of detection of the developed real-time PCR assay were 99.0%-100%, 92.9%-100%, 100%, <3%, and 8-58 copies/reaction, respectively. One assay cost only 2.34 USD. Application of the assay for the detection of the nine STIs in 535 vaginal swab samples collected from women in Vietnam yielded 532 positive cases (99.44%). Among the positive samples, 37.76% had one pathogen, with G. vaginalis (33.83%) as the most prevalent; 46.36% had two pathogens, with G. vaginalis + C. albicans as the most prevalent combination (38.13%); and 11.78%, 2.99%, and 0.56% had three, four, and five pathogens, respectively. In conclusion, the developed assay represents a sensitive and cost-effective molecular diagnostic tool for the detection of major STIs in Vietnam and is a model for the development of panel detections of common STIs in other countries.
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Enfermedades de Transmisión Sexual , Trichomonas vaginalis , Embarazo , Humanos , Femenino , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Chlamydia trachomatis , Trichomonas vaginalis/genéticaRESUMEN
ß-sitosterol derived from Clinacanthus nutans Lindau was tested for its in vitro osteogenic activity using MC3T3-E1 pre-osteoblasts. Our results indicated that ß-sitosterol was non-toxic to the cells cultured at a concentration <20 µg/mL. Treatment of the cells with ß-sitosterol significantly enhanced the alkaline phosphatase activity up to 210 and 204.6% at 5 and 10 µg/mL, respectively (P < .05). Similarly, the mineralization activity of the ß-sitosterol treated cells was elevated up to 134, 168, 118% at a concentration of 2.5, 5, and 10 µg/mL, respectively (P < .05). In addition, this compound up-regulated several marker genes for osteoblast differentiation, including runx2, osx and col I to 2, 2.5 and 5.6 folds at 10 µg/mL, respectively (P < .05). The expression of p38 and ERK proteins involved in the MAPK signal pathway related to mineralization and differentiation was also enhanced. Thus, the osteoblastogenic activity of ß-sitosterol was fully illustrated for the first time.
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Osteoblastos , Osteogénesis , Regulación hacia Arriba , Diferenciación Celular , Osteoblastos/metabolismoRESUMEN
Advanced deep learning (DL) algorithms may predict the patient's risk of developing breast cancer based on the Breast Imaging Reporting and Data System (BI-RADS) and density standards. Recent studies have suggested that the combination of multi-view analysis improved the overall breast exam classification. In this paper, we propose a novel multi-view DL approach for BI-RADS and density assessment of mammograms. The proposed approach first deploys deep convolutional networks for feature extraction on each view separately. The extracted features are then stacked and fed into a Light Gradient Boosting Machine (LightGBM) classifier to predict BI-RADS and density scores. We conduct extensive experiments on both the internal mammography dataset and the public dataset Digital Database for Screening Mammogra-phy (DDSM). The experimental results demonstrate that the proposed approach outperforms the single-view classification approach on two benchmark datasets by huge F1-score margins (+5% on the internal dataset and +10% on the DDSM dataset). These results highlight the vital role of combining multi-view information to improve the performance of breast cancer risk prediction.
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Neoplasias de la Mama , Aprendizaje Profundo , Benchmarking , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , MamografíaRESUMEN
BACKGROUND: Studies on symptom clusters among cancer patients have been conducted intensively. However, the concept seems not to be well defined, hindering its utilization in clinical practice. AIM: The aim of this paper is to reconceptualize symptom cluster and discuss areas of future research. RESULTS: A cluster of symptoms should not be viewed as simply as a group of symptoms appearing together. It should be clinically relevant, and symptom members should be interactive or have a mutual etiology. A cluster is declared as stable if its "quality" or "nature" is remained instead of merely having the same number of symptoms. Importantly, each symptom cluster should have a sentinel symptom. The sentinel symptom could be the one that predicts the presence of the cluster or could be the one that significantly interacts with other symptoms. The search for symptom clusters, which are common among various patient groups, might be helpful in some aspects. However, to better understand them, symptom clusters should be examined in specific populations. CONCLUSION: The nature of the relationship between symptom members, clinical relevance, sentinel symptom, stability, and prevalence are important features of a symptom cluster. More explorations into these properties by future studies are suggested.
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Neoplasias , Atención de Enfermería , Humanos , Neoplasias/complicaciones , SíndromeRESUMEN
Experience-dependent white matter plasticity offers new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human translational experiment combined myelin water imaging in humans and genetic fate-mapping of oligodendrocyte lineage cells in mice to investigate whether downhill locomotor rehabilitation that emphasizes eccentric muscle actions promotes white matter plasticity and recovery in chronic, incomplete spinal cord injury (SCI). In humans, of 20 individuals with SCI that enrolled, four passed the imaging screen and had myelin water imaging before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI + DH). One individual was excluded for imaging artifacts. Uninjured control participants (n = 7) had two myelin water imaging sessions within the same day. Changes in myelin water fraction (MWF), a histopathologically-validated myelin biomarker, were analyzed in a priori motor learning and non-motor learning brain regions and the cervical spinal cord using statistical approaches appropriate for small sample sizes. PDGFRα-CreERT2:mT/mG mice, that express green fluorescent protein on oligodendrocyte precursor cells and subsequent newly-differentiated oligodendrocytes upon tamoxifen-induced recombination, were either naive (n = 6) or received a moderate (75 kilodyne), contusive SCI at T9 and were randomized to downhill training (n = 6) or unexercised groups (n = 6). We initiated recombination 29 days post-injury, seven days prior to downhill training. Mice underwent two weeks of daily downhill training on the same 10% decline grade used in humans. Between-group comparison of functional (motor and sensory) and histological (oligodendrogenesis, oligodendroglial/axon interaction, paranodal structure) outcomes occurred post-training. In humans with SCI, downhill training increased MWF in brain motor learning regions (postcentral, precuneus) and mixed motor and sensory tracts of the ventral cervical spinal cord compared to control participants (P < 0.05). In mice with thoracic SCI, downhill training induced oligodendrogenesis in cervical dorsal and lateral white matter, increased axon-oligodendroglial interactions, and normalized paranodal structure in dorsal column sensory tracts (P < 0.05). Downhill training improved sensorimotor recovery in mice by normalizing hip and knee motor control and reducing hyperalgesia, both of which were associated with new oligodendrocytes in the cervical dorsal columns (P < 0.05). Our findings indicate that eccentric-focused, downhill rehabilitation promotes white matter plasticity and improved function in chronic SCI, likely via oligodendrogenesis in nervous system regions activated by the training paradigm. Together, these data reveal an exciting role for eccentric training in white matter plasticity and sensorimotor recovery after SCI.
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Rehabilitación Neurológica/métodos , Plasticidad Neuronal/fisiología , Desempeño Psicomotor/fisiología , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/rehabilitación , Sustancia Blanca/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Enfermedad Crónica , Prueba de Esfuerzo/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
On average, one person dies by suicide every 40 s. However, extant studies have largely focused on the risk factors for suicidal behaviors, not so much on the formation of suicidal thoughts. Therefore, we attempt to explain how suicidal thoughts arise and persist inside one's mind using a multifiltering information mechanism called Mindsponge. Bayesian analysis with Hamiltonian Markov Chain Monte Carlo (MCMC) technique was run on a dataset of multinational students (N = 268) of an international university in Japan. Item 9 in the PHQ-9 was used to survey suicidal ideation. The associations among four main variables, namely, (i) suicidal ideation, (ii) help-seeking willingness (informal and formal sources), (iii) sense of connectedness, and (iv) information inaccessibility (represented by being international students), were tested in four models. Sense of connectedness is negatively associated with suicidal ideation, but its effect becomes less impactful when interacting with international students. The impact of a sense of connectedness on informal help-seeking willingness (toward family members) among international students is also lessened. Informal help-seeking is negatively associated with suicidal ideation, whereas formal help is positive. The findings support our assumption on three fundamental conditions for preventing suicidal thoughts: (i) a high degree of belongingness, (ii) accessibility to help-related information, and (iii) healthy perceived cultural responses towards mental health. Therefore, systematically coordinated programs are necessary to effectively tackle suicidal ideation.
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Conducta de Búsqueda de Ayuda , Suicidio , Teorema de Bayes , Humanos , Japón , Ideación SuicidaRESUMEN
INTRODUCTION: Limited information exists on health care workers' (HCWs) perceptions about use of multidose vaccine vials and their preferences about doses per container (DPC). We present findings from qualitative studies conducted in Senegal, Vietnam, and Zambia to explore HCWs' behavior regarding opening vials and their perceptions and preferences for the number of doses in vials of BCG and measles-containing vaccine (MCV). Zambia and Senegal currently offer MCV in 10-dose vials and BCG in 20-dose vials; 10-dose vials are used for both vaccines in Vietnam. Unused doses in vials of these reconstituted vaccines must be discarded within 6 hours. METHODS: Key informant interviews (KIIs) were conducted with frontline HCWs in Senegal, Vietnam, and Zambia. In Senegal and Vietnam, the KIIs were conducted as part of broader formative research; in Zambia, KIIs were conducted in control districts using 10-dose MCV vials only and in intervention districts that switched from 10- to 5-dose vials during the study. During analysis, themes common to all 3 countries were synthesized. Critical themes relevant to country contexts were also examined. RESULTS: HCWs in all 3 countries preferred containers with fewer doses for BCG and MCV to reduce wastage and increase the likelihood of vaccinating every eligible child. HCWs in Senegal and HCWs using 10-dose vials in Zambia reported sending unvaccinated children away because not enough children were present to warrant opening a new vial. In Vietnam, where sessions are typically held monthly, and in Zambia when the 5-dose vials were used, almost all HCWs reported opening a vial of MCV for even 1 child. DISCUSSION: HCWs prefer vials with fewer DPC. Their concerns about balancing coverage and wastage influence their decisions to vaccinate every eligible child; and their perspectives are crucial to ensuring that all target populations are reached with vaccines in a timely manner.
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Programas de Inmunización , Vacunación , Niño , Personal de Salud , Humanos , Vacuna Antisarampión , Senegal , Vietnam , ZambiaRESUMEN
BACKGROUND: In 2016-2017, Vietnam's Ministry of Health (MoH) implemented an event-based surveillance (EBS) pilot project in six provinces as part of Global Health Security Agenda (GHSA) efforts. This manuscript describes development and design of tools for monitoring and evaluation (M&E) of EBS in Vietnam. METHODS: A strategic EBS framework was developed based on the EBS implementation pilot project's goals and objectives. The main process and outcome components were identified and included input, activities, outputs, and outcome indicators. M&E tools were developed to collect quantitative and qualitative data. The tools included a supervisory checklist, a desk review tool, a key informant interview guide, a focus group discussion guide, a timeliness form, and an online acceptability survey. An evaluation team conducted field visits for assessment of EBS 5-9 months after implementation. RESULTS: The quantitative data collected provided evidence on the number and type of events that were being reported, the timeliness of the system, and the event-to-signal ratio. The qualitative and subjective data collected helped to increase understanding of the system's field utility and acceptance by field staff, reasons for non-compliance with established guidelines, and other factors influencing implementation. CONCLUSIONS: The use of M&E tools for the EBS pilot project in Vietnam provided data on signals and events reported, timeliness of reporting and response, perceptions and opinions of implementers, and fidelity of EBS implementation. These data were valuable for Vietnam's MoH to understand the function of the EBS program, and the success and challenges of implementing this project in Vietnam.
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Monitoreo Epidemiológico , Salud Global , Brotes de Enfermedades , Humanos , Proyectos Piloto , Encuestas y Cuestionarios , VietnamRESUMEN
PURPOSE: To develop a non-invasive MRI-based methodology to visually and quantitatively assess the impact of head and chest rotations on the airway caliber. METHODS: An MRI table set-up was developed for independent rotations of the head and chest along B0 field and tested for feasibility using phantom scans. The accuracy of the head and chest rotations was validated with ten volunteer scans. A 3T MRI protocol was optimized to image the regions of interest (ROIs) that were the retropalatal (RP) and retroglossal (RG) sections of the upper airway. A workflow for data analysis was developed to assess the changes of the airway caliber following the independent head and chest rotations. RESULTS: A prototype MRI table setup was established with two separate plates each supporting and rotating the head or chest independently. Subject positioning and image acquisition were finished within seven minutes for each position. Thus, each subject MRI was set up with seven positions and completed for less than one hour. The implemented angles were within 0.3-degree deviation from the targeted angles. The data analysis workflow provided 2D and 3D visualization and quantification with the measurements of cross-sectional area, lateral and anterior-posterior distances of the ROIs. Sharp contrast of the airway and its surrounding tissues facilitated an automatic approach to ROI placement to minimize subjectivity. CONCLUSIONS: The 3T MRI data acquisition and analysis methodology could reliably assess the impact of head and chest rotations on the upper airway caliber to identify the optimal position for obstructive sleep apnea patients.
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Imagen por Resonancia Magnética , Monitoreo Fisiológico/métodos , Apnea Obstructiva del Sueño/diagnóstico por imagen , Adulto , Índice de Masa Corporal , Femenino , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Apnea Obstructiva del Sueño/fisiopatología , Adulto JovenRESUMEN
Community event-based surveillance aims to enhance the early detection of emerging public health threats and thus build health security. The Ministry of Health of Vietnam launched a community event-based surveillance pilot program in 6 provinces to improve the early warning functions of the existing surveillance system. An evaluation of the pilot program took place in 2017 and 2018. Data from this evaluation were analyzed to determine which factors were associated with increased detection and reporting. Results show that a number of small, local events were detected and reported through community event-based surveillance, supporting the notion that it would also facilitate the rapid detection and reporting of potentially larger events or outbreaks. The study showed the value of supportive supervision and monitoring to sustain community health worker reporting and the importance of conducting evaluations for community event-based surveillance programs to identify barriers to effective implementation.
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Brotes de Enfermedades/prevención & control , Vigilancia de la Población/métodos , Evaluación de Programas y Proyectos de Salud , Salud Pública , Salud Global , Humanos , Proyectos Piloto , Medidas de Seguridad , VietnamRESUMEN
Surveillance and outbreak reporting systems in Vietnam required improvements to function effectively as early warning and response systems. Accordingly, the Ministry of Health of Vietnam, in collaboration with the US Centers for Disease Control and Prevention, launched a pilot project in 2016 focusing on community and hospital event-based surveillance. The pilot was implemented in 4 of Vietnam's 63 provinces. The pilot demonstrated that event-based surveillance resulted in early detection and reporting of outbreaks, improved collaboration between the healthcare facilities and preventive sectors of the ministry, and increased community participation in surveillance and reporting.
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Control de Enfermedades Transmisibles , Brotes de Enfermedades/prevención & control , Vigilancia de la Población , Instituciones de Salud , Hospitales , Humanos , Vietnam/epidemiologíaRESUMEN
Cutaneous metastases typically occur in only a small minority of breast cancer patients. Clinical appearance can vary, but lesions often present as isolated dermal nodules with superficial discoloration or a change in texture on the chest ipsilateral to the primary breast malignancy. We report the case of a woman with metastatic adenocarcinoma of the breast presenting with diffuse cutaneous nodules with no surface changes. The nodules were almost undetectable clinically and had minimal elevation, making them difficult to detect, especially without palpation. A punch biopsy showed positive cytokeratin immunostaining consistent with the markers for the primary breast cancer. A review of the literature on cutaneous metastases from breast adenocarcinomas also is provided.
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Adenocarcinoma/patología , Neoplasias de la Mama/patología , Neoplasias Cutáneas/patología , Adenocarcinoma/secundario , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Cutáneas/secundarioRESUMEN
BACKGROUND: It is a critical unmet need to predict chemosensitivity in muscle-invasive bladder cancer patients who receive neoadjuvant chemotherapy (NAC). Quantification of tumor heterogeneity has been shown to be useful in the assessment of therapeutic response. Apparent diffusion coefficient (ADC) is derived from diffusion weighted MRI (DWI) to quantify the water diffusivity which characterizes micro-cellularity in tumor tissues. OBJECTIVE: The aim of this study is to assess if a quantitative measurement of ADC heterogeneity in bladder tumors can be a predictor of therapeutic response to NAC. MATERIALS AND METHODS: Twenty patients with pT2 bladder cancer have been included in this study. Patient MRI was performed on a 3T system with DWI prior to NAC. Regions of interest (ROIs) were placed over the whole tumor volume on ADC maps to acquire a data matrix of voxel-wise ADC values for each patient. We performed histogram analysis on each ADC data matrix to calculate uniformity (U) and entropy (E). These quantities were subsequently correlated with the patient's response to chemotherapy. Statistical significance was found with Pâ<â0.05. RESULTS: Fifteen patients were categorized as responders, and five as non-responders. The data showed that tumors of responders were significantly higher in U (Pâ=â0.01) and lower in E (Pâ<â0.01) than non-responders. This finding indicates that resistant tumors were more heterogeneous in their spatial distribution of ADC values. While this difference in ADC heterogeneity was not always visually recognizable, it could be quantified by the data analytics. CONCLUSIONS: This study demonstrates that the quantitative readout of tumor heterogeneity in micro-cellularity is associated with the patient's defined response to chemotherapy. Quantification of tumor ADC heterogeneity may provide useful information to enable the prediction of chemotherapeutic response prior to the treatment to improve patient outcomes.
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OBJECTIVES: To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. METHODS: Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. RESULTS: Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. CONCLUSIONS: The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. KEY POINTS: ⢠Heterogeneity is an intrinsic characteristic of tumoral tissue. ⢠Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. ⢠Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. ⢠The quantification helps differentiate malignant from benign urinary bladder tissue.
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Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Anciano , Cistectomía , Diagnóstico Diferencial , Difusión , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Enfermedades de la Vejiga Urinaria/diagnóstico por imagen , Enfermedades de la Vejiga Urinaria/patología , Enfermedades de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , AguaRESUMEN
We report syntheses of new superconducting metal-doped MoSe2 materials (MxMoSe2). The superconducting MxMoSe2 samples were prepared using a liquid NH3 technique, and can be represented as '(NH3)yMxMoSe2'. The Tcs of these materials were approximately 5.0 K, independent of x and the specific metal atom. X-ray diffraction patterns of (NH3)yNaxMoSe2 were recorded using polycrystalline powders. An increase in lattice constant c showed that the Na atom was intercalated between MoSe2 layers. The x-independence of c was observed in (NH3)yNaxMoSe2, indicating the formation of a stoichiometric compound in the entire x range, which is consistent with the x-independence of Tc. A metallic edge of the Fermi level was observed in the photoemission spectrum at 30 K, demonstrating its metallic character in the normal state. Doping of MoSe2 with Li and K also yielded superconductivity. Thus, MoSe2 is a promising material for designing new superconductors, as are other transition metal dichalcogenides.
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BACKGROUND: To evaluate whether parallel radiofrequency transmission (mTX) can improve the symmetry of the left and right femoral arteries in dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of prostate and bladder cancer. METHODS: Eighteen prostate and 24 bladder cancer patients underwent 3.0 Tesla DCE-MRI scan with a single transmission channel coil. Subsequently, 21 prostate and 21 bladder cancer patients were scanned using the dual channel mTX upgrade. The precontrast signal ( S0) and the maximum enhancement ratio (MER) were measured in both the left and the right femoral arteries. Within the patient cohort, the ratio of S0 and MER in the left artery to that in the right artery ( S0_LR, MER_LR) was calculated with and without the use of mTX. Left to right asymmetry indices for S0 ( S0_LRasym) and MER ( MER_LRasym) were defined as the absolute values of the difference between S0_LR and 1, and the difference between MER_LR and 1, respectively. RESULTS: S0_LRasym, and MER_LRasym were 0.21 and 0.19 for prostate cancer patients with mTX, and 0.43 and 0.45 for the ones imaged without it (P < 0.001). Also, for the bladder cancer patients, S0_LRasym, and MER_LRasym were 0.11 and 0.9 with mTX, while imaging without it yielded 0.52 and 0.39 (P < 0.001). CONCLUSION: mTX can significantly improve left-to-right symmetry of femoral artery precontrast signal and contrast enhancement.
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Arteria Femoral/metabolismo , Arteria Femoral/patología , Gadolinio DTPA/farmacocinética , Angiografía por Resonancia Magnética/métodos , Neoplasias Pélvicas/irrigación sanguínea , Neoplasias Pélvicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Simulación por Computador , Medios de Contraste/farmacocinética , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Persona de Mediana Edad , Modelos Biológicos , Pelvis/irrigación sanguínea , Pelvis/patología , Ondas de Radio , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To apply k-means clustering of two pharmacokinetic parameters derived from 3T dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the chemotherapeutic response in bladder cancer at the mid-cycle timepoint. MATERIALS AND METHODS: With the predetermined number of three clusters, k-means clustering was performed on nondimensionalized Amp and kep estimates of each bladder tumor. Three cluster volume fractions (VFs) were calculated for each tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline to mid-cycle were correlated with the tumor's chemotherapeutic response. Receiver-operating-characteristics curve analysis was used to evaluate the performance of each cluster VF change as a biomarker of chemotherapeutic response in bladder cancer. RESULTS: The k-means clustering partitioned each bladder tumor into cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3 (high kep and low Amp). The changes of all three cluster VFs were found to be associated with bladder tumor response to chemotherapy. The VF change of cluster 2 presented with the highest area-under-the-curve value (0.96) and the highest sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value. CONCLUSION: The k-means clustering of the two DCE-MRI pharmacokinetic parameters can characterize the complex microcirculatory changes within a bladder tumor to enable early prediction of the tumor's chemotherapeutic response.
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Cisplatino/uso terapéutico , Gadolinio DTPA/farmacocinética , Interpretación de Imagen Asistida por Computador/métodos , Modelos Biológicos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Medios de Contraste/farmacocinética , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Estadísticos , Evaluación de Resultado en la Atención de Salud/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
OBJECTIVES: The objective of this study was to assess the capability of T2-weighted magnetic resonance imaging (T2W-MRI) and the additional diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) using multitransmit 3 T in the localization of bladder cancer. MATERIALS AND METHODS: This prospective study was approved by the local institutional review board. Thirty-six patients were included in the study and provided informed consent. Magnetic resonance imaging scans were performed with T2W-MRI and DCE-MRI on a 3-T multitransmit system. Two observers (with 12 and 25 years of experience) independently interpreted T2W-MRI before DCE-MRI data (maps of pharmacokinetic parameters) to localize bladder tumors. The pathological examination of cystectomy bladder specimens was used as a reference criteria standard. The McNemar test was performed to evaluate the differences in sensitivity, specificity, and accuracy. Scores of κ were calculated to assess interobserver agreement. RESULTS: The sensitivity, specificity, and accuracy of the localization with T2W-MRI alone were 81% (29/36), 63% (5/8), and 77% (34/44) for observer 1 and 72% (26/36), 63% (5/8), and 70% (31/44) for observer 2. With additional DCE-MRI available, these values were 92% (33/36), 75% (6/8), and 89% (39/44) for observer 1 and 92% (33/36), 63% (5/8), and 86% (38/44) for observer 2. Dynamic contrast-enhanced MRI significantly (P<0.01) improved the sensitivity and accuracy for observer 2. For the 23 patients treated with chemotherapy, DCE-MRI also significantly (P<0.02) improved the sensitivity and accuracy of bladder cancer localization with T2W-MRI alone for observer 2. Scores of κ were 0.63 for T2W-MRI alone and 0.78 for additional DCE-MRI. Of 7 subcentimeter malignant tumors, 4 (57%) were identified on T2W images and 6 (86%) were identified on DCE maps. Of 11 malignant tumors within the bladder wall thickening, 6 (55%) were found on T2W images and 10 (91%) were found on DCE maps. CONCLUSIONS: Compared with conventional T2W-MRI alone, the addition of DCE-MRI improved interobserver agreement as well as the localization of small malignant tumors and those within bladder wall thickening.
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Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste/farmacocinética , Femenino , Gadolinio DTPA/farmacocinética , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
Yeast was the first microorganism domesticated by mankind. Indeed, the production of bread and alcoholic beverages such as beer and wine dates from antiquity, even though the fact that the origin of alcoholic fermentation is a microorganism was not known until the nineteenth century. The use of starter cultures in yeast industries became a common practice after methods for the isolation of pure yeast strains were developed. Moreover, effort has been undertaken to improve these strains, first by classical genetic methods and later by genetic engineering. In general, yeast strain development has aimed at improving the velocity and efficiency of the respective production process and the quality of the final products. This review highlights the achievements in genetic engineering of Saccharomyces yeast strains applied in food and beverage industry.