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BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).
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Hipocampo/patología , Trastornos por Estrés Postraumático/patología , Trastornos por Estrés Postraumático/fisiopatología , Adulto , Estudios Transversales , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Trastornos por Estrés Postraumático/diagnóstico por imagen , Heridas y Lesiones/complicaciones , Adulto JovenRESUMEN
BACKGROUND: The matrix assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI-TOF MS) technology has revolutionized the field of microbiology by facilitating precise and rapid species identification. Recently, machine learning techniques have been leveraged to maximally exploit the information contained in MALDI-TOF MS, with the ultimate goal to refine species identification and streamline antimicrobial resistance determination. OBJECTIVES: The aim was to systematically review and evaluate studies employing machine learning for the analysis of MALDI-TOF mass spectra. DATA SOURCES: Using PubMed/Medline, Scopus and Web of Science, we searched the existing literature for machine learning-supported applications of MALDI-TOF mass spectra for microbial species and antimicrobial susceptibility identification. STUDY ELIGIBILITY CRITERIA: Original research studies using machine learning to exploit MALDI-TOF mass spectra for microbial specie and antimicrobial susceptibility identification were included. Studies focusing on single proteins and peptides, case studies and review articles were excluded. METHODS: A systematic review according to the PRISMA guidelines was performed and a quality assessment of the machine learning models conducted. RESULTS: From the 36 studies that met our inclusion criteria, 27 employed machine learning for species identification and nine for antimicrobial susceptibility testing. Support Vector Machines, Genetic Algorithms, Artificial Neural Networks and Quick Classifiers were the most frequently used machine learning algorithms. The quality of the studies ranged between poor and very good. The majority of the studies reported how to interpret the predictors (88.89%) and suggested possible clinical applications of the developed algorithm (100%), but only four studies (11.11%) validated machine learning algorithms on external datasets. CONCLUSIONS: A growing number of studies utilize machine learning to optimize the analysis of MALDI-TOF mass spectra. This review, however, demonstrates that there are certain shortcomings of current machine learning-supported approaches that have to be addressed to make them widely available and incorporated them in the clinical routine.
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Bacterias/clasificación , Bacterias/efectos de los fármacos , Aprendizaje Automático , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Antibacterianos/uso terapéutico , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
PURPOSE: Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. METHODS: In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. RESULTS: FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway. CONCLUSION: FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.
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Carcinoma/genética , Proteínas de Unión a Ácidos Grasos/genética , Expresión Génica , Neoplasias de la Próstata/genética , ARN Mensajero/metabolismo , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Carcinoma/secundario , Carcinoma/cirugía , Estudios de Casos y Controles , Factor Nuclear 3-alfa del Hepatocito/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Cuidados Paliativos , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Prostatectomía , Hiperplasia Prostática/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Proteínas Represoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Resección Transuretral de la PróstataRESUMEN
Ectopic thymic tissue outside its core position in the antero-superior mediastinum is quite common owing to the complexity of embryonal thymus development, whereby reported prevalence values (1 to 90%) are heavily dependent on the method of investigation and the intensity of the workup. The debated prevalence and relevance of ectopic thymic tissue and its accessibility underlie the ongoing discussion whether modern, minimally invasive thymectomy strategies can match the proven benefit of the radical transsternal thymectomy procedure for the treatment of Myasthenia gravis. In this context, the following article covers the etiology, prevalence, and location of normal-looking, reactive, and neoplastic ectopic thymic tissue. Furthermore, ectopic tissues and tumors inside or adjacent to the thymus are mentioned.
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Coristoma , Miastenia Gravis , Neoplasias del Timo , Humanos , Timectomía , TimoRESUMEN
INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.
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Invasive pulmonary aspergillosis (IPA) is one of the major complications in immunocompromised patients. The mainstay of diagnostic imaging is non-enhanced chest-computed-tomography (CT), for which various non-specific signs for IPA have been described. However, contrast-enhanced CT pulmonary angiography (CTPA) has shown promising results, as the vessel occlusion sign (VOS) seems to be more sensitive and specific for IPA in hematologic patients. The aim of this study was to evaluate the diagnostic accuracy of CTPA in a larger cohort including non-hematologic immunocompromised patients. CTPA studies of 78 consecutive immunocompromised patients with proven/probable IPA were analyzed. 45 immunocompromised patients without IPA served as a control group. Diagnostic performance of CTPA-detected VOS and of radiological signs that do not require contrast-media were analyzed. Of 12 evaluable radiological signs, five were found to be significantly associated with IPA. The VOS showed the highest diagnostic performance with a sensitivity of 0.94, specificity of 0.71 and a diagnostic odds-ratio of 36.8. Regression analysis revealed the two strongest independent radiological predictors for IPA to be the VOS and the halo sign. The VOS is highly suggestive for IPA in immunocompromised patients in general. Thus, contrast-enhanced CTPA superior over non-contrast_enhanced chest-CT in patients with suspected IPA.
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Angiografía por Tomografía Computarizada , Huésped Inmunocomprometido , Aspergilosis Pulmonar/diagnóstico , Intensificación de Imagen Radiográfica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos , Niño , Preescolar , Angiografía por Tomografía Computarizada/métodos , Angiografía por Tomografía Computarizada/normas , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Neutropenia/patología , Aspergilosis Pulmonar/tratamiento farmacológico , Aspergilosis Pulmonar/etiología , Aspergilosis Pulmonar/microbiología , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology. METHODS: To assess tissue morphology and fiber composition, histochemical staining was performed. RNA expression of healthy and fibrotic tissue of twelve patients was analyzed using the human miRNA panel v3 and mRNA PanCancer pathway panel on the nCounter gene1 system and qRT-PCR. Differential expression data analysis was performed using the nSolver software implementing the R-based advanced pathway analysis tool. miRWalk2.0 was used for miRNA target prediction. RESULTS: More linearized tissue architecture, increased collagens, and decreased elastic fibers were observed in VUAS samples. 23 miRNAs and 118 protein coding genes were differentially expressed (p < 0.01) in fibrotic tissue. miRNA target prediction and overlap analysis indicated an interaction of the strongest deregulated miRNAs with 29 deregulated mRNAs. Pathway analysis revealed alterations in DNA repair, cell cycle regulation, and TGF-beta signaling. qRT-PCR confirmed differential expression of top deregulated miRNAs and mRNAs. CONCLUSIONS: In VUAS tissue, severe alterations on mRNA and miRNA level are found. These consistent changes give insights into the pathogenesis of VUAS after radical prostatectomy and point to future options for transcriptomics-based risk stratification and targeted therapies.
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Anastomosis Quirúrgica , MicroARNs/metabolismo , Complicaciones Posoperatorias/genética , Prostatectomía , Neoplasias de la Próstata/cirugía , ARN Mensajero/metabolismo , Uretra/cirugía , Estrechez Uretral/genética , Vejiga Urinaria/cirugía , Anciano , Constricción Patológica/genética , Constricción Patológica/patología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma , Estrechez Uretral/patologíaRESUMEN
Reactive and neoplastic thymic pathologies are the main considerations in the case of masses in the anterior and middle part of the mediastinum, while neurogenic tumors are predominant in the posterior mediastinum (which are not dealt with here). In neonates and infants, the commonest pathologies in the anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac tumors and cysts predominate. In children over 5 years of age, lymphomas are the commonest mass lesions whereas thymomas and thymic carcinomas are rare. In addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic hyperplasia after chemotherapy must be considered. Although rare at all ages, sarcomas must be considered in the differential diagnosis from birth onwards and throughout adolescence. Based on the report of a rare case of recurrent TTH, the differential diagnosis of this benign but potentially life-threatening condition is discussed.
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Enfermedades Linfáticas/diagnóstico , Timo/patología , Hiperplasia del Timo/diagnóstico , Neoplasias del Timo/diagnóstico , Adolescente , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Enfermedades Linfáticas/patología , Masculino , Quiste Mediastínico/diagnóstico , Quiste Mediastínico/patología , Miastenia Gravis/diagnóstico , Miastenia Gravis/patología , Sarcoma/diagnóstico , Sarcoma/patología , Teratoma/diagnóstico , Teratoma/patología , Timectomía , Timoma/diagnóstico , Timoma/patología , Hiperplasia del Timo/patología , Neoplasias del Timo/patología , Tomografía Computarizada por Rayos XRESUMEN
Thymomas are rare tumors but are one of the most common mediastinal neoplasms in adults and exhibit an enormous variability in histological, biological and genetic features. The morphological spectrum within a given entity is enormous and some tumors with histological patterns of more than one entity are more common than pure histological subtypes. Due to a lack of subtype-specific markers classification of thymomas often requires complex diagnostic algorithms. The refined presentation including the definition of obligatory and optional features and of diagnostic immunohistochemical profiles, is the focus of the new World Health Organization (WHO) classification of thymomas, aiming at improving diagnostic reproducibility. This review highlights novel aspects of the WHO classification of thymomas and addresses typical differential diagnostic challenges with a focus on diagnostic pitfalls.
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Timoma/clasificación , Timoma/patología , Neoplasias del Timo/clasificación , Neoplasias del Timo/patología , Adulto , Algoritmos , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Clasificación Internacional de Enfermedades , Timoma/diagnóstico , Timoma/genética , Timo/patología , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/genética , Organización Mundial de la SaludRESUMEN
Thymic carcinomas (TC) are approximately 10 times less prevalent than thymomas but of high clinical relevance because they are more aggressive, less frequently resectable than thymomas and usually refractory to classical and targeted long-term treatment approaches. Furthermore, in children and adolescents TC are more frequent than thymomas and particularly in this age group, germ cell tumors need to be a differential diagnostic consideration. In diagnostic terms pathologists face two challenges: a), the distinction between thymic carcinomas and thymomas with a similar appearance and b), the distinction between TC and histologically similar metastases and tumor extensions from other primary tumors. Overcoming these diagnostic challenges is the focus of the new WHO classification of thymic epithelial tumors. The objectives of this review are to highlight novel aspects of the WHO classification of thymic carcinomas and to address therapeutically relevant diagnostic pitfalls.
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Timoma/diagnóstico , Timoma/patología , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Adolescente , Niño , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Neoplasias de Células Germinales y Embrionarias/clasificación , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/terapia , Timoma/clasificación , Timoma/terapia , Timo/patología , Neoplasias del Timo/clasificación , Neoplasias del Timo/terapia , Organización Mundial de la SaludRESUMEN
Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the rate of spontaneous emission can be greatly enhanced by placing the quantum system in a resonant cavity. This effect has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, and is essential for the realization of high-efficiency single-photon sources. Here we report the application of this idea to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity with a high quality factor and a small mode volume, we reach the regime in which spontaneous emission constitutes the dominant mechanism of spin relaxation. The relaxation rate is increased by three orders of magnitude as the spins are tuned to the cavity resonance, demonstrating that energy relaxation can be controlled on demand. Our results provide a general way to initialize spin systems into their ground state and therefore have applications in magnetic resonance and quantum information processing. They also demonstrate that the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point at which quantum fluctuations have a marked effect on the spin dynamics; as such, they represent an important step towards the coherent magnetic coupling of individual spins to microwave photons.
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INTRODUCTION: Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000. MATERIALS AND METHODS: A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches. RESULTS: These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stage I and II thymomas, whereas in stage III thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy. CONCLUSION: The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options.
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Tumor Carcinoide/patología , Carcinoma/patología , Timoma/patología , Neoplasias del Timo/patología , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirugía , Carcinoma/diagnóstico , Carcinoma/cirugía , Terapia Combinada , Diagnóstico Diferencial , Humanos , Estadificación de Neoplasias , Pronóstico , Timectomía , Timoma/diagnóstico , Timoma/cirugía , Timo/patología , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/cirugíaRESUMEN
The detection and characterization of paramagnetic species by electron spin resonance (ESR) spectroscopy is widely used throughout chemistry, biology and materials science, from in vivo imaging to distance measurements in spin-labelled proteins. ESR relies on the inductive detection of microwave signals emitted by the spins into a coupled microwave resonator during their Larmor precession. However, such signals can be very small, prohibiting the application of ESR at the nanoscale (for example, at the single-cell level or on individual nanoparticles). Here, using a Josephson parametric microwave amplifier combined with high-quality-factor superconducting microresonators cooled at millikelvin temperatures, we improve the state-of-the-art sensitivity of inductive ESR detection by nearly four orders of magnitude. We demonstrate the detection of 1,700 bismuth donor spins in silicon within a single Hahn echo with unit signal-to-noise ratio, reduced to 150 spins by averaging a single Carr-Purcell-Meiboom-Gill sequence. This unprecedented sensitivity reaches the limit set by quantum fluctuations of the electromagnetic field instead of thermal or technical noise, which constitutes a novel regime for magnetic resonance. The detection volume of our resonator is â¼ 0.02 nl, and our approach can be readily scaled down further to improve sensitivity, providing a new versatile toolbox for ESR at the nanoscale.
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Amplificadores Electrónicos , Espectroscopía de Resonancia por Spin del Electrón/instrumentación , Espectroscopía de Resonancia por Spin del Electrón/métodos , Microquímica/instrumentación , Nanopartículas/análisis , Nanopartículas/química , Aire Acondicionado/instrumentación , Síndrome de Creutzfeldt-Jakob , Diseño de Equipo , Análisis de Falla de Equipo , Microondas , Miniaturización , Teoría Cuántica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Relación Señal-RuidoRESUMEN
Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).
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Magnetismo , Nanopartículas de Magnetita , Neoplasias Pancreáticas/diagnóstico , Animales , Línea Celular Tumoral , Compuestos Férricos/química , Galectina 1/química , Galectina 1/metabolismo , Humanos , Imagen por Resonancia Magnética , Ratones , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Cintigrafía , Radiofármacos , Proteínas Recombinantes/química , Albúmina Sérica/química , Activador de Tejido Plasminógeno/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
INTRODUCTION: The standardized characterization of angiogenesis is crucial in the field of tissue engineering as sufficient blood supply is the limiting factor of mass transfer. However, reliable algorithms that provide a straight forward and observer-independent assessment of new vessel formation are still lacking. We propose an automatic observer-independent quantitative method (including downloadable source code) to analyze vascularization using two-dimensional microscopic images of histological cross-sections and advanced postprocessing, based on a 'positive- and negative-experts' model and a (corrected) nearest neighbour classification, in a vascularized tissue engineering model. MATERIALS AND METHODS: An established angioinductive rat arteriovenous loop model was used to compare the new automatic analysis with a common 2D method and a µCT algorithm. Angiogenesis was observed at three different time points (5, 10 and 15 days). RESULTS: In line with previous results, formation of functional new vessels that arose from the venous graft was evident within the three-dimensional construct and a significant (p < 0.05) increase in vessel count and area was observed over time. The proposed automatic analysis obtained precise values for vessel count and vessel area that were similar to the manually gained data. The algorithm further provided vectorized parameterization of the newly formed vessels for advanced statistical analysis. Compared to the µCT-based three-dimensional analyses, the presented two-dimensional algorithm was superior in terms of small vessel detection as well as cost and time efficiency. CONCLUSIONS: The quantitative evaluation method, using microscopic images of stained histological sections, 'positive- and negative-experts'-based vessel segmentation, and nearest neighbour classification, provides a user-independent and precise but also time- and cost-effective tool for the analysis of vascularized constructs. Our algorithm, which is freely available to the public, outperforms previous approaches especially in terms of unambiguous vessel classification and statistical analyses.
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Algoritmos , Vasos Sanguíneos/crecimiento & desarrollo , Vasos Sanguíneos/ultraestructura , Neovascularización Fisiológica , Ingeniería de Tejidos/métodos , Animales , Automatización , Vasos Sanguíneos/anatomía & histología , Humanos , Modelos Teóricos , RatasRESUMEN
By combination of two independent approaches, nuclear resonant inelastic x-ray scattering and first-principles calculations in the framework of density functional theory, we demonstrate significant changes in the element-resolved vibrational density of states across the first-order transition from the ferromagnetic low temperature to the paramagnetic high temperature phase of LaFe(13-x)Si(x). These changes originate from the itinerant electron metamagnetism associated with Fe and lead to a pronounced magneto-elastic softening despite the large volume decrease at the transition. The increase in lattice entropy associated with the Fe subsystem is significant and contributes cooperatively with the magnetic and electronic entropy changes to the excellent magneto- and barocaloric properties.
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We demonstrate an all-electrical donor nuclear spin polarization method in silicon by exploiting the tunable interaction of donor bound electrons with a two-dimensional electron gas, and achieve over two orders of magnitude nuclear hyperpolarization at T=5 K and B=12 T with an in-plane magnetic field. We also show an intricate dependence of nuclear polarization effects on the orientation of the magnetic field, and both hyperpolarization and antipolarization can be controllably achieved in the quantum Hall regime. Our results demonstrate that donor nuclear spin qubits can be initialized through local gate control of electrical currents without the need for optical excitation, enabling the implementation of nuclear spin qubit initialization in dense multiqubit arrays.
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We demonstrate that an antiferromagnetic coupling between paramagnetic Fe-porphyrin molecules and ultrathin Co and Ni magnetic films on Cu(100) substrates can be established by an intermediate layer of atomic oxygen. The coupling energies have been determined from the temperature dependence of x-ray magnetic circular dichroism measurements. By density functional theory+U calculations the coupling mechanism is shown to be superexchange between the Fe center of the molecules and Co surface-atoms, mediated by oxygen.
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We use single-spin resonant spectroscopy to study the spin structure in the orbital excited state of a diamond nitrogen-vacancy (N-V) center at room temperature. The data show that the excited-state spin levels have a zero-field splitting that is approximately half of the value of the ground state levels, a g factor similar to the ground state value, and a hyperfine splitting approximately 20x larger than in the ground state. In addition, the width of the resonances reflects the electronic lifetime in the excited state. We also show that the spin level splitting can significantly differ between N-V centers, likely due to the effects of local strain, which provides a pathway to control over the spin Hamiltonian and may be useful for quantum-information processing.
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To further determine whether genistein (GEN) modulation of the immune responses was related to its endocrine-disrupting properties and time of exposure, pregnant C57BL/6 mice were exposed to GEN at 0-1250 ppm in feed starting on day 14 of gestation. The C57BL/6 offspring were exposed to GEN in utero and lactationally, and through feed after weaning until postnatal day 42. In dams, exposure to GEN increased the terminal body weight (250 and 1250 ppm), the number of splenic T cells and NK cells (250 ppm), and the activity of NK cells (250 ppm). In F(1) males, GEN increased the terminal body and spleen weights (25 and 250 ppm), the number of CD4(+)CD8(+) and CD4(-)CD8(+) thymocytes (25 ppm), and the number of splenic T cell subsets and NK cells (25 and 250 ppm). Moreover, splenic NK cell activity and anti-CD3-mediated splenocyte proliferation were increased in all treatment groups. In F(1) females, the percentages of CD4(-)CD8(+) and CD4(-)CD8(-) thymocytes (25 and 250 ppm), and CD4(+)CD8(-) and CD4(+)CD8(+) splenocytes (25 and 250 ppm) were increased. In contrast, the percentage and number of CD4(+)CD8(+) thymocytes were decreased (250 ppm). Exposure to GEN decreased the percentages of splenic NK cells in all treatment groups, and decreased the activity of splenic NK cells at the 25 ppm concentration. Additionally, evaluation of CD25(+) and CD44(+) expression by thymocytes indicated that the decrease in the percentage of CD44(+)CD25(+) thymocytes was at least partially responsible for the decrease in the percentage of CD4(-)CD8(-) thymocytes in F(1) male mice. Overall, the results demonstrate that GEN can modulate the immune system in both adult and developing C57BL/6 mice in a dose-specific manner. The gender-specific effects of GEN on the immune responses in F(1) mice suggest that GEN may modulate the immune system by functioning as either an estrogen agonist or antagonist. The differential effects of GEN on thymocytes in F(1) male and female mice indicate that GEN immunomodulation might be related to its effect on thymus.