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Fear behaviors are regulated by adaptive mechanisms that dampen their expression in the absence of danger. By studying circuits and the molecular mechanisms underlying this adaptive response, we show that cholinergic neurons of the medial habenula reduce fear memory expression through GABAB presynaptic excitation. Ablating these neurons or inactivating their GABAB receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABAB receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABAB mediates excitation by amplifying presynaptic Ca(2+) entry through Cav2.3 channels and potentiating co-release of glutamate, acetylcholine, and neurokinin B to excite interpeduncular neurons. Activating the receptors for these neurotransmitters or enhancing neurotransmission with a phosphodiesterase inhibitor reduces fear responses of both wild-type and GABAB mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABAB receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders.
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Neurônios Colinérgicos/metabolismo , Medo/fisiologia , Habenula/fisiologia , Memória/fisiologia , Receptores de GABA-B/metabolismo , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais , Neurotransmissores/metabolismo , Transmissão SinápticaRESUMO
Film bulk acoustic-wave resonators (FBARs) are widely utilized in the field of radio frequency (RF) filters due to their excellent performance, such as high operation frequency and high quality. In this paper, we present the design, fabrication, and characterization of an FBAR filter for the 3.0 GHz-3.2 GHz S-band. Using a scandium-doped aluminum nitride (Sc0.2Al0.8N) film, the filter is designed through a combined acoustic-electromagnetic simulation method, and the FBAR and filter are fabricated using an eight-step lithographic process. The measured FBAR presents an effective electromechanical coupling coefficient (keff2) value up to 13.3%, and the measured filter demonstrates a -3 dB bandwidth of 115 MHz (from 3.013 GHz to 3.128 GHz), a low insertion loss of -2.4 dB, and good out-of-band rejection of -30 dB. The measured 1 dB compression point of the fabricated filter is 30.5 dBm, and the first series resonator burns out first as the input power increases. This work paves the way for research on high-power RF filters in mobile communication.
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Product selectivity of solar-driven CO2 reduction and H2O oxidation reactions has been successfully controlled by tuning the spatial distance between Pt/Au bimetallic active sites on different crystal facets of CeO2 catalysts. The replacement depth of Ce atoms by monatomic Pt determines the distance between bimetallic sites, while Au clusters are deposited on the surface. This space configuration creates a favourable microenvironment for the migration of active hydrogen species (*H). The *H is generated via the activation of H2O on monatomic Pt sites and migrate towards Au clusters with a strong capacity for CO2 adsorption. Under concentrated solar irradiation, selectivity of the (100) facet towards CO is 100%, and the selectivity of the (110) and (111) facets towards CH4 is 33.5% and 97.6%, respectively. Notably, the CH4 yield on the (111) facet is as high as 369.4 µmol/g/h, and the solar-to-chemical energy efficiency of 0.23% is 33.8 times higher than that under non-concentrated solar irradiation. The impacts of high-density flux photon and thermal effects on carriers and *H migration at the microscale are comprehensively discussed. This study provides a new avenue for tuning the spatial distance between active sites to achieve optimal product selectivity.
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GABAB receptors in habenula cholinergic neurons mediate strong presynaptic excitation and control aversive memory expression. K+ channel tetramerization domain (KCTD) proteins are key interacting partners of GABAB receptors; it remains unclear whether and how KCTDs contribute to GABAB excitatory signaling. Here, we show that KCTD8 and KCTD12 in these neurons facilitate the GABAB receptors expression in axonal terminals and contribute to presynaptic excitation by GABAB receptors. Genetically knocking out KCTD8/12/16 or KCTD8/12, but not other combinations of the three KCTD isoforms, substantially reduced GABAB receptors-mediated potentiation of glutamate release and presynaptic Ca2+ entry in response to axonal stimulation, whereas they had no effect on GABAB-mediated inhibition in the somata of cholinergic neurons within the habenulo-interpeduncular pathway in mice of either sex. The physiological phenotypes were associated with a significant decrease in the GABAB expression within the axonal terminals but not the somata. Overexpressing either KCTD8 or KCTD12 in the KCTD8/12/16 triple knock-out mice reversed the changes in axonal GABAB expression and presynaptic excitation. In mice lacking the KCTDs, aversion-predicting cues produced stronger neuronal activation in the interpeduncular nucleus, and the infusion of GABAB agonist in this nucleus produced a weaker effect on fear extinction. Collectively, our results reveal isoform-specific roles of KCTD proteins in enriching the axonal expression of GABAB receptors, facilitating their presynaptic signaling, and modulating aversion-related memory processes.SIGNIFICANCE STATEMENT GABAB receptors represent the principal inhibitory neurotransmitter receptor, but they mediate strong presynaptic excitation in the habenulo-interpeduncular pathway and modulate aversion memory expression. KCTD proteins are integral constituents of GABAB receptors. By analyzing the physiological, neuroanatomical, and behavioral phenotypes of multiple KCTD knock-out mouse lines, we show that KCTD8 and KCTD12 facilitate the axonal expression and hence presynaptic excitation of GABAB receptors in habenula cholinergic neurons and control cued-aversion memory formation and expression in the habenulo-interpeduncular pathway. These results expand the physiological and behavioral functions of KCTDs in modulating the brain neural circuits.
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Axônios , Neurônios Colinérgicos , Habenula , Peptídeos e Proteínas de Sinalização Intracelular , Receptores de GABA-B , Receptores de GABA , Animais , Axônios/metabolismo , Neurônios Colinérgicos/metabolismo , Extinção Psicológica , Medo/fisiologia , Habenula/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Knockout , Receptores de GABA/metabolismo , Receptores de GABA-B/genética , Receptores de GABA-B/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.
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Schistosoma japonicum , Esquistossomose , Humanos , Feminino , Animais , Schistosoma japonicum/genética , Esquistossomose/veterinária , Imunoglobulina G , Reprodução , Anexinas/metabolismoRESUMO
Schistosomiasis is an important zoonotic disease affecting up to 40 kinds of animals and is responsible for â¼250 million human cases per year. Due to the extensive use of praziquantel for the treatment of parasitic diseases, drug resistance has been reported. Consequently, novel drugs and effective vaccines are urgently needed for sustained control of schistosomiasis. Targeting reproductive development of Schistosoma japonicum could contribute to the control of schistosomiasis. In this study, five highly expressed proteins (S. japonicum large subunit ribosomal protein L7e, S. japonicum glutathione S-transferase class-mu 26 kDa isozyme, S. japonicum UDP-galactose-4-epimerase and two hypothetical proteins SjCAX70849 and SjCAX72486) in 18, 21, 23, and 25-day mature female worms compared to single-sex infected female worms were selected based on our previous proteomic analysis. Quantitative real-time polymerase chain reaction analysis and long-term interference with small interfering RNA were performed to identify the biological functions of these five proteins. The transcriptional profiles suggested that all five proteins participated in the maturation of S. japonicum. RNA interference against these proteins resulted in morphological changes to S. japonicum. The results of an immunoprotection assay revealed that immunization of mice with recombinant SjUL-30 and SjCAX72486 upregulated production of immunoglobulin G-specific antibodies. Collectively, the results demonstrated that these five differentially expressed proteins were vital to reproduction of S. japonicum and, thus, are potential candidate antigens for immune protection against schistosomiasis.
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Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Minorias Sexuais e de Gênero , Feminino , Humanos , Animais , Camundongos , Proteômica , Praziquantel/farmacologiaRESUMO
The large amount of schistosome eggs produced by mature female worms not only induce major pathological damage to the host but also lead to the transmission of schistosomiasis. Mature female schistosome worms need constant pairing contact with a male partner as male signaling is indispensable to female growth, development, and reproduction. The gynecophoral canal protein (GCP), a cell-surface glycoprotein, plays a potential role in the interaction between males and females and in stimulating female development and maturation. In this study, a yeast two-hybrid cDNA library of Schistosoma japonicum (Sj) parasites 18 days post-infection (dpi) was constructed; the Sjgcp gene was inserted into a pGBKT7-BD bait plasmid and used as a bait protein to screen for its molecular interactions using a yeast mating procedure. Twenty-four prey proteins that interacted with the SjGCP were selected after excluding false positives; the interactions between S.japonicum lethal giant larvae (SjLGL) and SjGCP, S.japonicum type V collagen (SjColV) and SjGCP, were verified by co-immunoprecipitation. The RNA interference against SjGCP, SjColV and SjGCP + SjColV led to severe underdevelopment of tegument in male worms and vitelline globules in female worms as well as reduced reproductive capacity of the females. Collectively, SjGCP and its interacting proteins may play pivotal roles in growth and development. The findings also suggested that SjGCP and its interacting protein partners might represent new candidate targets for drug development against schistosomiasis.
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Schistosoma japonicum , Esquistossomose Japônica , Animais , Feminino , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Masculino , Saccharomyces cerevisiae/genética , Schistosoma japonicum/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
The reverse projection protocol results in fast phase-contrast imaging thanks to its compatibility with conventional computed-tomography scanning. Many researchers have proposed variants. However, all these reverse projection methods in grating-based phase-contrast imaging are built on the hypothesis of the synchronous phase of reference shifting curves in the whole field of view. The hypothesis imposes uniformity and alignment requirements on the gratings, thus the field of view is generally limited. In this paper, a generalized reverse projection method is presented analytically for the case of non-uniform reference in grating-based phase tomography. The method is demonstrated by theoretical derivation, numerical simulations and synchrotron radiation experiments. The influence of imaging position to sensitivity, and the phase-wrapping phenomenon are also discussed. The proposed method combines the advantages of the high efficiency of the reverse projection method and the universal applicability of the phase-stepping method. The authors believe that the method would be used widely in fast and dose-constrained imaging.
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Optical upconversion that converts infrared light into visible light is of significant interest for broad applications in biomedicine, imaging, and displays. Conventional upconversion materials rely on nonlinear light-matter interactions, exhibit incidence-dependent efficiencies, and require high-power excitation. We report an infrared-to-visible upconversion strategy based on fully integrated microscale optoelectronic devices. These thin-film, ultraminiaturized devices realize near-infrared (â¼810 nm) to visible [630 nm (red) or 590 nm (yellow)] upconversion that is linearly dependent on incoherent, low-power excitation, with a quantum yield of â¼1.5%. Additional features of this upconversion design include broadband absorption, wide-emission spectral tunability, and fast dynamics. Encapsulated, freestanding devices are transferred onto heterogeneous substrates and show desirable biocompatibilities within biological fluids and tissues. These microscale devices are implanted in behaving animals, with in vitro and in vivo experiments demonstrating their utility for optogenetic neuromodulation. This approach provides a versatile route to achieve upconversion throughout the entire visible spectral range at lower power and higher efficiency than has previously been possible.
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Miniaturização , Optogenética/instrumentação , Próteses e Implantes , Animais , Arsenicais , Comportamento Animal , Materiais Biocompatíveis , Mapeamento Encefálico/instrumentação , Desenho de Equipamento , Gálio , Raios Infravermelhos , Camundongos , Camundongos Nus , Optogenética/métodos , Fótons , Ratos , Semicondutores , Córtex Somatossensorial/fisiologia , Tela SubcutâneaRESUMO
A three-image algorithm is proposed to retrieve the sample's transmission, refraction and dark-field information in hard X-ray grating interferometry. Analytical formulae of the three-image algorithm are theoretically derived and presented, and evaluated by proof-of-principle synchrotron radiation experiments. The results confirm the feasibility of the proposed algorithm. The novelty of the proposed algorithm is that it allows versatile and tunable multimodal X-ray imaging by substantially relaxing the existing limitations on the lateral grating position. Furthermore, this algorithm can also be adapted for samples with negligible refraction, reducing the number of required sample measurements to two. Furthermore, the noise properties of the retrieved images are investigated in terms of the standard deviations. Theoretical models are presented and verified by synchrotron radiation measurements. It is shown that the noise standard deviations exhibit strong dependence on the lateral grating position, especially in the case of refraction and dark-field images. Further noise reduction and dose reduction can thus be possible by optimizing the lateral grating position for a selected region of interest. Those results can serve as general guidelines to optimize the data acquisition scheme for specific applications and problems.
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Stepped wedge designed trials are a type of cluster-randomized study in which the intervention is introduced to each cluster in a random order over time. This design is often used to assess the effect of a new intervention as it is rolled out across a series of clinics or communities. Based on a permutation argument, we derive a closed-form expression for an estimate of the intervention effect, along with its standard error, for a stepped wedge design trial. We show that these estimates are robust to misspecification of both the mean and covariance structure of the underlying data-generating mechanism, thereby providing a robust approach to inference for the intervention effect in stepped wedge designs. We use simulations to evaluate the type 1 error and power of the proposed estimate and to compare the performance of the proposed estimate to the optimal estimate when the correct model specification is known. The limitations, possible extensions, and open problems regarding the method are discussed.
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Biometria/métodos , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Adolescente , Adulto , Viés , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Análise por Conglomerados , Simulação por Computador , Intervalos de Confiança , Interpretação Estatística de Dados , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Humanos , Incidência , Tamanho da Amostra , Parceiros Sexuais , Washington/epidemiologia , Adulto JovemRESUMO
Eggs produced by bisexual infected mature female worms (MF) of Schistosoma japonicum are important in the transmission of the parasite and responsible for the pathogenesis of schistosomiasis. The single-sex infected female worms (SF) cannot mature and do not produce normal eggs; also they do not induce severe damage to the host. In this study, the microRNA (miRNA) expression profiles of 25d MF and 25d SF were investigated through Solexa deep-sequencing technology to explore the developmental mechanisms of schistosome female worms. There were 36 differentially expressed miRNA, 20 up-regulated and 16 down-regulated found in MF/SF worms, including some development related miRNA such as bantam (ban), let-7, miR-124, miR-8, miR-1, miR-7. There were 166 target genes of up-regulated miRNA and 201 target genes of down-regulated miRNA after comparing the target gene prediction software results with RNA-Seq transcriptome results. Analysis of the target genes shows that different ones are involved in MF and SF worms in Gene Ontology terms, with a similar situation in KEGG. This observation indicates that different genes regulated by differentially expressed miRNA take part in MF and SF and lead to differential sexual status. This means that the sexual status of female worms is regulated by miRNA.
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Expressão Gênica , MicroRNAs/genética , RNA de Helmintos/genética , Schistosoma japonicum/genética , Animais , Feminino , Regulação da Expressão Gênica , MicroRNAs/metabolismo , RNA de Helmintos/metabolismo , Schistosoma japonicum/crescimento & desenvolvimentoRESUMO
BACKGROUND: The adverse reactions that are caused by drugs are potentially life-threatening problems. Comprehensive knowledge of adverse drug reactions (ADRs) can reduce their detrimental impacts on patients. Detecting ADRs through clinical trials takes a large number of experiments and a long period of time. With the growing amount of unstructured textual data, such as biomedical literature and electronic records, detecting ADRs in the available unstructured data has important implications for ADR research. Most of the neural network-based methods typically focus on the simple semantic information of sentence sequences; however, the relationship of the two entities depends on more complex semantic information. METHODS: In this paper, we propose multihop self-attention mechanism (MSAM) model that aims to learn the multi-aspect semantic information for the ADR detection task. first, the contextual information of the sentence is captured by using the bidirectional long short-term memory (Bi-LSTM) model. Then, via applying the multiple steps of an attention mechanism, multiple semantic representations of a sentence are generated. Each attention step obtains a different attention distribution focusing on the different segments of the sentence. Meanwhile, our model locates and enhances various keywords from the multiple representations of a sentence. RESULTS: Our model was evaluated by using two ADR corpora. It is shown that the method has a stable generalization ability. Via extensive experiments, our model achieved F-measure of 0.853, 0.799 and 0.851 for ADR detection for TwiMed-PubMed, TwiMed-Twitter, and ADE, respectively. The experimental results showed that our model significantly outperforms other compared models for ADR detection. CONCLUSIONS: In this paper, we propose a modification of multihop self-attention mechanism (MSAM) model for an ADR detection task. The proposed method significantly improved the learning of the complex semantic information of sentences.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Redes Neurais de Computação , Semântica , Atenção , HumanosRESUMO
BACKGROUND: Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. METHODS: The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). RESULTS: Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0-8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). CONCLUSION: Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02120469. Registered 18 April 2014.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Fadiga/induzido quimicamente , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estomatite/induzido quimicamente , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
A single-image method is proposed for quantitative phase retrieval in hard X-ray grating interferometry. This novel method assumes a quasi-homogeneous sample, with a constant ratio between the real and imaginary parts of its complex refractive index. The method is first theoretically derived and presented, and then validated by synchrotron radiation experiments. Compared with the phase-stepping method, the presented approach abandons grating scanning and multiple image acquisition, and is therefore advantageous in terms of its simplified acquisition procedure and reduced data-collection times, which are especially important for applications such as in vivo imaging and phase tomography. Moreover, the sample's phase image, instead of its first derivative, is directly retrieved. In particular, the stripe artifacts encountered in the integrated phase images are significantly suppressed. The improved quality of the retrieved phase images can be beneficial for image interpretation and subsequent processing. Owing to its requirement for a single image and its robustness against noise, the present method is expected to find use in potential investigations in diverse applications.
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BACKGROUND: Controversy in axillary reverse mapping in axillary lymph node dissection (ALND) possibly results from incomplete recognition of the arm lymphatic system (ALS) and its compromise to oncological safety. The iDEntification and Preservation of ARm lymphaTic system (DEPART) technique facilitates complete identification of ALS; therefore, its use may decrease the occurrence of arm lymphedema. This study aimed to examine the arm lymphedema rate, locoregional recurrence, and feasibility to perform DEPART in ALND. METHODS: Patients from February 2013 to October 2017 from two tertiary referral centers were randomly assigned to two groups. In the study group, indocyanine green and methylene blue (MB) were utilized to identify arm sentinel nodes, and 0.1 ml MB was injected into the arm sentinel nodes to reveal the subsequent-echelon nodes and lymphatics. Gross arm lymph nodes were examined by intraoperative partial frozen section and were removed if positive. Arm lymphedema, local recurrence, regional recurrence, and distant metastasis were recorded at different follow-up examinations. RESULTS: Arm sentinel nodes were identified in 573 (83.2%) patients. Subsequent-echelon nodes and lymphatics were visualized in 558 (97.4%) patients. Metastatic arm nodes were identified in 38 (6.8%) patients. The arm lymphedema rate was 3.3% (18/543) in the study group versus 15.3% (99/648) in the control group (p < 0.001) after 37-month median follow-up. Regional recurrence showed no difference between the two groups (1.4% and 1.2%, respectively) (p = 0.392). CONCLUSIONS: DEPART can benefit breast cancer patients who undergo ALND, reducing the arm lymphedema rate without adversely affecting the morbidity of regional recurrence.
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Braço/cirurgia , Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Sistema Linfático , Linfedema/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Tratamentos com Preservação do Órgão/métodos , Adulto , Idoso , Braço/patologia , Axila , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Procedimentos de Cirurgia PlásticaRESUMO
BACKGROUND: Accurate and complete response evaluation after treatment is important to implement individualized therapy for gastric cancer. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and in-line X-ray phase contrast imaging (ILXPCI) in the assessment of the therapeutic efficacy by transforming growth factor beta 1 (TGF-ß1) inhibition. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Thirty nude mice subcutaneous xenotransplantation tumor model of gastric cancer for DKI and 10 peritoneal metastasis nude mice model for ILXPCI. FIELD STRENGTH/SEQUENCE: Examinations before and serially at 7, 14, 21, and 28 days after TGF-ß1 inhibition treatment were performed at 3T MRI including T2 -weighted imaging (T2 WI) and DKI with five b values of 0, 500, 1000, 1500, 2000 s/mm2 ; ILXPCI examinations were performed at 14 days after treatment. ASSESSMENT: DKI parameters (apparent diffusion coefficient [ADC], diffusivity [D] and kurtosis [K]) were calculated by two experienced radiologists after postprocessing. STATISTICAL TESTS: For the differences in all the parameters between the baseline and each timepoint for both the treated and the control mice, the Mann-Whitney test was used. The Spearman correlation test was used to evaluate correlations among the DKI parameters and corresponding pathologic necrosis fraction (NF). RESULTS: ADC, D, and K values were significantly different between the two groups after treatment (P < 0.05). Serial measurements in the treated group showed that the ADC, D, and K values were significantly different at 7, 14, 21, and 28 days compared with baseline (P < 0.05). There were significant correlations between DKI parameters and NF (ADC, r = 0.865, P < 0.001; D, r = 0.802, P < 0.001; K, r = -0.944, P < 0.001). The ILXPCI results in the treated group showed a stronger absorption area than the control group. DATA CONCLUSION: DKI may be used to evaluate the complete course therapeutic effects of gastric cancer induced by TGF-ß1 inhibition, and the ILXPCI technique will improve the tumor microstructure resolution. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1553-1564.
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Meios de Contraste/farmacologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Gástricas/patologia , Raios XRESUMO
A new prism-array lens for high-energy X-ray focusing has been constructed using an array of different prisms obtained from different parabolic structures by removal of passive parts of material leading to a multiple of 2π phase variation. Under the thin-lens approximation the phase changes caused by this lens for a plane wave are exactly the same as those caused by a parabolic lens without any additional corrections when they have the same focal length, which will provide good focusing; at the same time, the total transmission and effective aperture of this lens are both larger than those of a compound kinoform lens with the same focal length, geometrical aperture and feature size. This geometry can have a large aperture that is not limited by the feature size of the lens. Prototype nickel lenses with an aperture of 1.77â mm and focal length of 3â m were fabricated by LIGA technology, and were tested using CCD camera and knife-edge scan method at the X-ray Imaging and Biomedical Application Beamline BL13W1 at Shanghai Synchrotron Radiation Facility, and provided a focal width of 7.7â µm and a photon flux gain of 14 at an X-ray energy of 50â keV.
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Microscopy techniques using visible photons, x-rays, neutrons, and electrons have made remarkable impact in many scientific disciplines. The microscopic data can often be expressed as the convolution of the spatial distribution of certain properties of the specimens and the inherent response function of the imaging system. The x-ray grating interferometer (XGI), which is sensitive to the deviation angle of the incoming x-rays, has attracted significant attention in the past years due to its capability in achieving x-ray phase contrast imaging with low brilliance source. However, the comprehensive and analytical theoretical framework is yet to be presented. Herein, we propose a theoretical framework termed angular signal radiography (ASR) to describe the imaging process of the XGI system in a classical, comprehensive and analytical manner. We demonstrated, by means of theoretical deduction and synchrotron based experiments, that the spatial distribution of specimens' physical properties, including absorption, refraction and scattering, can be extracted by ASR in XGI. Implementation of ASR in XGI offers advantages such as simplified phase retrieval algorithm, reduced overall radiation dose, and improved image acquisition speed. These advantages, as well as the limitations of the proposed method, are systematically investigated in this paper.
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BACKGROUND: The outstanding functional importance of the brain implies a strong need for brain imaging modalities. However, the current imaging approaches that target the brain in rodents remain suboptimal. OBJECTIVE AND METHODS: In this paper, X-ray propagation-based phase contrast imaging combined with equally sloped tomography (PPCI-EST) was employed to nondestructively investigate the mouse brain. RESULTS: The grey and white matters, which have extremely small differences in electron density, were clearly discriminated. The fine structures, including the corpus callosum (cc), the optic chiasma (ox) and the caudate putamen (CPu), were revealed. Compared to the filtered back projection reconstruction, the PPCI-EST significantly reduce projection number while maintaining sufficient image quality. CONCLUSIONS: It could be a potential tool for fast and low-dose phase-contrast imaging to biomedical specimens.