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To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery.According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences.A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p 0.05).For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.

Introduction: Alzheimer’s disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. Methods: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). Results: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. Conclusion: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

Glioblastoma is a central nervous malignancy with a very poor prognosis. This study attempted to explore the role of exosomes induced by low-dose radiation-induced (ldrEXOs) and ldrEXOs-derived circ-METRN in glioblastoma progression and radioresistance at the molecular, cellular, animal, and clinical levels. Results in the present study revealed that low-dose radiation stimulated the secretion of ldrEXOs which delivered high levels of circ-METRN. And circ-METRN-abundant ldrEXOs increased the expression of γ-H2AX, indicating an efficient DNA damage-repair process in glioblastoma cells. The ldrEXOs-derived circ-METRN enhanced the glioblastoma progression and radioresistance via miR-4709-3p/GRB14/PDGFRα pathway. Up-regulating PDGFRα can rescue the tumor-promoting function of ldrEXOs in groups previously treated with inhibition of GRB14. Additionally, in-vivo experiments revealed that treatments with ldrEXOs promoted the growth of xenografted tumors and shortened the survival period. Furthermore, clinical researches indicated that circ-METRN may be transported into the bloodstream by exosomes in the early stages of fractionated radiotherapy. It has important clinical values to detect the serum exosomal circ-METRN in the early stage of radiotherapy, which is not only conducive to predict radioresistance and prognosis but also to assist MRI diagnosis in detecting the very early recurrence of glioblastoma. In summary, this study reveals for the first time that low-dose radiation-induced exosomal circ-METRN plays an oncogenic role in glioblastoma progression and radioresistance through miR-4709-3p/GRB14/PDGFRα pathway, providing mechanistic insights into the roles of circRNAs and a valuable marker for therapeutic targets in glioblastoma.

Optical Coherence Tomography Angiography (OCTA) is a novel, non-invasive imaging modality of retinal capillaries at micron resolution. Recent studies have correlated macular OCTA vascular measures with retinal disease severity and supported their use as a diagnostic tool. However, these measurements mostly rely on a few summary statistics in retinal layers or regions of interest in the two-dimensional (2D) en face projection images. To enable 3D and localized comparisons of retinal vasculature between longitudinal scans and across populations, we develop a novel approach for mapping retinal vessel density from OCTA images. We first obtain a high-quality 3D representation of OCTA-based vessel networks via curvelet-based denoising and optimally oriented flux (OOF). Then, an effective 3D retinal vessel density mapping method is proposed. In this framework, a vessel density image (VDI) is constructed by diffusing the vessel mask derived from OOF-based analysis to the entire image volume. Subsequently, we utilize a non-linear, 3D OCT image registration method to provide localized comparisons of retinal vasculature across subjects. In our experimental results, we demonstrate an application of our method for longitudinal qualitative analysis of two pathological subjects with edema during the course of clinical care. Additionally, we quantitatively validate our method on synthetic data with simulated capillary dropout, a dataset obtained from a normal control (NC) population divided into two age groups and a dataset obtained from patients with diabetic retinopathy (DR). Our results show that we can successfully detect localized vascular changes caused by simulated capillary loss, normal aging, and DR pathology even in presence of edema. These results demonstrate the potential of the proposed framework in localized detection of microvascular changes and monitoring retinal disease progression.

The short association fibers or U-fibers connect two neighboring gyri and travel in the superficial white matter (SWM) beneath the cortical layer. These U-fibers are essential for the understanding of neurodevelopment and neurodegeneration. However, the complex structures and the high curvature of the U-fibers lead to erroneous streamlines reconstruction of the traditional tractography since the volume-based tractography cannot use the biological characteristic of U-fibers that they tightly beneath the cortical layer. In this work, we proposed a surface-based framework for probabilistic tracking of the U-fibers on the triangular mesh of the SWM. We develop a novel approach to project the fiber orientation distributions (FODs) data onto the tangent space of the SWM surface. With the projected FODs, an advanced probabilistic tracking technique, which regularizes the streamlines based on the intrinsic geometry of the surface, is developed to reconstruct the highly bent U-fibers on the SWM surface. In the experiment, we demonstrate our method based on the high-resolution diffusion imaging data from the Human Connectome Project (HCP). We quantitatively compare the proposed method with state-of-the-art volume-based tractography from MRTrix and another surface-based tractography on the U-fibers of the central sulcus. Moreover, we show the reconstructed U-fibers on the parietal lobe and frontal lobe. The results show that our method outperforms the other two methods and successfully reconstructs the U-fibers on the cortical regions with high intersubject variability.

Susceptibility induced distortion is a major artifact that affects the diffusion MRI (dMRI) data analysis. In the Human Connectome Project (HCP), the state-of-the-art method adopted to correct this kind of distortion is to exploit the displacement field from the B0 image in the reversed phase encoding images. However, both the traditional and learning-based approaches have limitations in achieving high correction accuracy in certain brain regions, such as brainstem. By utilizing the fiber orientation distribution (FOD) computed from the dMRI, we propose a novel deep learning framework named DistoRtion Correction Net (DrC-Net), which consists of the U-Net to capture the latent information from the 4D FOD images and the spatial transformer network to propagate the displacement field and back propagate the losses between the deformed FOD images. The experiments are performed on two datasets acquired with different phase encoding (PE) directions including the HCP and the Human Connectome Low Vision (HCLV) dataset. Compared to two traditional methods topup and FODReg and two deep learning methods S-Net and flow-net, the proposed method achieves significant improvements in terms of the mean squared difference (MSD) of fractional anisotropy (FA) images and minimum angular difference between two PEs in white matter and also brainstem regions. In the meantime, the proposed DrC-Net takes only several seconds to predict a displacement field, which is much faster than the FODReg method.

Pulmonary fibrosis (PF) is a progressive interstitial lung disease with limited treatment options. The incidence and prevalence of PF is increasing with age, cell senescence has been proposed as a pathogenic driver, the clearance of senescent cells could improve lung function in PF. FOXO4-D-Retro-Inverso (FOXO4-DRI), a synthesis peptide, has been reported to selectively kill senescent cells in aged mice. However, it remains unknown if FOXO4-DRI could clear senescent cells in PF and reverse this disease. In this study, we explored the effect of FOXO4-DRI on bleomycin (BLM)-induced PF mouse model. We found that similar as the approved medication Pirfenidone, FOXO4-DRI decreased senescent cells, downregulated the expression of senescence-associated secretory phenotype (SASP) and attenuated BLM-induced morphological changes and collagen deposition. Furthermore, FOXO4-DRI could increase the percentage of type 2 alveolar epithelial cells (AEC2) and fibroblasts, and decrease the myofibroblasts in bleomycin (BLM)-induced PF mouse model. Compared with mouse and human lung fibroblast cell lines, FOXO4-DRI is inclined to kill TGF-β-induced myofibroblast in vitro. The inhibited effect of FOXO4-DRI on myofibroblast lead to a downregulation of extracellular matrix (ECM) receptor interaction pathway in BLM-induced PF. Above all, FOXO4-DRI ameliorates BLM-induced PF in mouse and may be served as a viable therapeutic option for PF.

Childhood obesity is associated with negative physiological and cognitive health outcomes. The hippocampus is a diverse subcortical structure involved in learned feeding behaviors and energy regulation, and research has shown that the hippocampus is vulnerable to the effects of excess adiposity. Previous studies have demonstrated reduced hippocampal volume in overweight and obese children, however it is unclear if certain sub-regions are selectively affected. The purpose of this study was to determine how excess body weight influences regional hippocampal surface morphology and memory performance in a large cross-sectional cohort of 588 children and adolescents between 8.33 and 19.92 years of age using body mass index expressed as a percentage of the 95(th) percentile cutoff (%BMIp95). We demonstrate %BMIp95 is associated with reduced radial thickness in the superior anterior region of the left hippocampus, and this relationship is predominantly driven by children younger than 14 years. We also found %BMIp95 was associated with worse performance on a spatial episodic memory task and this relationship was partially mediated by the radial thickness of the significant shape cluster. These results demonstrate the differential influence of excess body weight on regional hippocampal structure and hippocampal-dependent behavior in children and adolescents.

We report a patient with autism-like deficits in emotional connectedness, executive dysfunction, and ataxia beginning at age 39. He had compound heterozygous variants in SPG7 (A510V and 1552+1 G>T ...

3D optical coherence tomography angiography (OCT-A) is a novel and non-invasive imaging modality for analyzing retinal diseases. The studies of microvasculature in 2D en face projection images have been widely implemented, but comprehensive 3D analysis of OCT-A images with rich depth-resolved microvascular information is rarely considered. In this paper, we propose a robust, effective, and automatic 3D shape modeling framework to provide a high-quality 3D vessel representation and to preserve valuable 3D geometric and topological information for vessel analysis. Effective vessel enhancement and extraction steps by means of curvelet denoising and optimally oriented flux (OOF) filtering are first designed to produce 3D microvascular networks. Afterwards, a novel 3D data representation of OCT-A microvasculature is reconstructed via advanced mesh reconstruction techniques. Based on the 3D surfaces, shape analysis is established to extract novel shape-based microvascular area distortion via the Laplace-Beltrami eigen-projection. The extracted feature is integrated into a graph-cut segmentation system to categorize large vessels and small capillaries for more precise shape analysis. The proposed framework is validated on a dedicated repeated scan dataset including 260 volume images and shows high repeatability. Statistical analysis using the surface area biomarker is performed on small capillaries to avoid the effect of tailing artifact from large vessels. It shows significant differences (p < 0.001) between DR stages on 100 subjects in a OCTA-DR dataset. The proposed shape modeling and analysis framework opens the possibility for further investigating OCT-A microvasculature in a new perspective.

A series of silver coordination complexes (CCs) have been synthesized through self-assembly of five pyridine-substituted tetraphenylethylene stereoisomer ligands with silver ions (named Ag-TPE-2by-1-E, Ag-TPE-2by-2-E, Ag-TPE-2by-2-Z, Ag-TPE-2by-3-E, and Ag-TPE-2by-3-Z). These silver CCs show distinct topologies including beaded chain frameworks, linear structures, and discrete metallacycles. The single-crystal analysis results reveal the critical role of the space distribution of the coordination site and stereoisomer ligands in controlling the silver CCs' geometry configuration and modulating the optical properties. Luminescent investigations revealed that Ag-TPE-2by-2-E, Ag-TPE-2by-2-Z, Ag-TPE-2by-3-E, and Ag-TPE-2by-3-Z possess obvious mechanocharomic behaviors, which can be achieved several reversible cycles through repeated grinding and methanol soaking processes. However, the Ag-TPE-2by-1-E showed tenacious stability toward mechanical grinding and temperature. Thus, these silver CCs provide a good platform to investigate the influence of the space distribution of the coordination site of ligands on their geometry and mechanocharomic properties.

Introduction The present study aimed to explore the role of miR-499a-5p and its molecular mechanism in cervical cancer (CC). Methods Quantitative real-time PCR (QRT-PCR) and Western blotting were performed to detect the expression of miR-499a-5p and eukaryotic translation initiation factor 4E (eIF4E) in CC tissues and cell lines. The proliferation, migration, and invasion of CC cells were detected by MTT assay, wound healing assay, and Transwell assay. Apoptosis was evaluated by flow cytometry and alterations of apoptosis-related genes. The effect of miR-499a-5p on epithelial-mesenchymal transition (EMT) was examined by determining the protein levels of EMT-associated genes. Then, colony formation assay was used to determine the radiosensitivity of CC cells. A dual-luciferase reporter assay was performed to confirm the direct target of miR-499a-5p. Results MiR-499a-5p was significantly downregulated in CC tissues and cell lines. Overexpression of miR-499a-5p or eIF4E knockdown markedly inhibited cell proliferation, invasion, migration, and EMT, and enhanced apoptosis. eIF4E was predicted and verified as a target gene of miR-499a-5p. The influence of miR-499a-5p upregulation on proliferation, apoptosis, invasion, migration, EMT, and radiosensitivity was abrogated by eIF4E overexpression. Discussion MiR-499a-5p promoted the apoptosis and radiosensitivity and inhibited proliferation, invasion, migration, and EMT by directly targeting eIF4E in CC cells.

Diabetic retinopathy (DR) is a significant microvascular complication of diabetes mellitus and a leading cause of vision impairment in working age adults. Optical coherence tomography (OCT) is a routinely used clinical tool to observe retinal structural and thickness alterations in DR. Pathological changes that alter the normal anatomy of the retina, such as intraretinal edema, pose great challenges for conventional layer-based analysis of OCT images. We present an alternative approach for the automated analysis of OCT volumes in DR research based on nonlinear registration. In this paper, we first obtain an anatomically consistent volume of interest (VOI) in different OCT images via carefully designed masking and affine registration. After that, efficient B-spline transformations are computed using stochastic gradient descent optimization. Using the OCT volumes of normal controls, for which layer-based segmentation works well, we demonstrate the accuracy of our registration-based analysis in aligning layer boundaries. By nonlinearly registering the OCT volumes of DR subjects to an atlas constructed from normal controls and measuring the Jacobian determinant of the deformation, we can simultaneously visualize tissue contraction and expansion due to DR pathology. Tensor-based morphometry (TBM) can also be performed for quantitative analysis of local structural changes. In our experimental results, we apply our method to a dataset of 105 subjects and demonstrate that volumetric OCT registration and TBM analysis can successfully detect local retinal structural alterations due to DR.

Background: Taxane-based regimens that are frequently used in adjuvant chemotherapy in early triple-negative breast cancer (TNBC) include a three-drug regimen (TAC and AC-T) and a two-drug regimen (TA and TC). Whether pathological lymph node stage guides taxane-based de-escalating chemotherapies in TNBC in adjuvant setting is still unclear. Methods: We retrospectively examined 381 patients with early TNBC over a median follow-up period of 75.9 months and compared the disease-free survival (DFS) and overall survival (OS) of patients who received adjuvant taxane-based three-drug chemotherapy and two-drug chemotherapy according to pathological lymph node stage (negative, pN0; 1-3 positive, pN1; 4-9 positive, pN2). Results: In 222 pN0 patients, the taxane-based three-drug regimen was not superior to the two-drug regimen. In 159 pN1-2 patients, the taxane-based three-drug regimen significantly improved DFS (5-year DFS rate, 78.2% vs. 46.9%; log-rank p=0.0002) and OS (5-year OS rate, 90.7% vs. 64.3%; log-rank p=0.0001) compared with the two-drug regimen. In a multivariable Cox regression analysis of pN1-2 patients, after adjustment for clinical characteristics, the taxane-based three-drug regimen significantly decreased the risk of recurrence (adjusted HR, 0.37; 95% CI, 0.22 to 0.64; p=0.0004) and death (adjusted HR, 0.22; 95% CI, 0.10 to 0.48; p=0.0001) compared with the two-drug regimen. Conclusions: The taxane-based chemotherapy triplet is superior to the chemotherapy doublet in patients with one to nine positive lymph nodes but not node-negative TNBC in adjuvant setting. These data suggest that pathological lymph node stage leads to de-escalating chemotherapy strategies in operable TNBC patients.

A series of N-heterocycle-tethered organoboranes B1–B5 were synthesized and fully characterized. All these compounds contain a robust 5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracene (DBNA) core which plays a role as a Lewis acid site. Study of the different N-heterocycles as Lewis base moieties reveals that n-butyl-1H-1,2,4-triazolyl functionalized compounds (B1–B3) exhibit the dynamic switching of the intermolecular B–N bond in response to heat stimulus, leading to unusual reversible emission intensity enhancement at elevated temperature, while n-hexyl-1H-1,2,3-triazolyl attached compounds (B4–B5) only display thermal emission quenching behaviors. The different stimuli-responsive properties in solutions may be attributed to the position of the substituent alkyl chains which influence the torsion of the molecules, leading to different affinity of intermolecular B–N interactions. Single crystal X-ray diffraction analysis further confirms the dimeric species formation of B1–B3 in solid state. Furthermore, all compounds exhibit good mechanochromism.

Background Locally advanced cervical cancer (LACC), FIGO stage equal or more than IB1 is treated with chemotherapy and external beam radiotherapy followed by brachytherapy. However, treatment failure and distant metastasis still remain a major problem. Bioinformatics analysis was used to comprehensively evaluate the intrinsic resistance to treatment in LACC. We selected cytokine-like protein 1 (Cytl1), a novel cytokine, for validation by immunochemistry assays (IHC). Materials and methods The Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to identify significant prognostic differentially expressed genes (DEGs). The CIBERSORT and ESTIMATE algorithms was performed to validate the genetic risk score model. A total of 113 tissues were evaluated by IHC. Kaplan-Meier curves and the log-rank test were applied for survival analysis. Results One thousand and twenty-one genes, consisting of 663 upregulated and 358 downregulated genes, were screened out in the GSE56363 cohort. KEGG and GO pathway enrichment methods was used to analyze the abundant DEGs to find the common characteristics. A genetic risk score model which formed by fifteen genes was established from GSE56363 and validated in the TCGA discovery set. We performed the CIBERSORT and ESTIMATE algorithms to find the difference of immune related signature between the high- and low-risk group to quantify the prognostic value of the fifteen-gene risk model. Among the 22 immune cell types, CD8 T cells, resting CD4 T cells, resting mast cells, activated mast cells, monocytes, neutrophil granulocyte were significantly different between high- and low-risk group. Immune-checkpoints (LAG3 and PDCD1) were highly expressed, and associated with poor prognosis in LACC. IHC demonstrated that cytl1 overexpression was positively associated with poor overall survival (P = 0.01). Cytl1 expression was closely correlated with CD8+T cell low-expression in LACC (r = 0.889, P = 0.066). Conclusion This study identified a novel fifteen-gene signature biomarker for predicting the treatment effect of LACC. Moreover, the current results demonstrated that cytl1was overexpressed and associated with poor prognosis in LACC. Cytl1 may be a potential prognostic marker and novel therapeutic target for LACC.

The occurrence of radioresistance is a clinical obstacle to endometrial cancer (EC) treatment and induces tumor relapse. In this study, we found that tumor-associated macrophages (TAMs) enriched in EC specimens were determined to present an M2-like phenotype. In vitro, the coculture of M2-polarized macrophages significantly downregulated the radiosensitivity of EC cells by releasing exosomes. Hsa_circ_0001610 was found to be abundant in exosomes derived from M2-polarized macrophages (EXOs), and hsa_circ_0001610 knockdown eliminated the reduction effect of EXOs on the radiosensitivity of EC cells. The following mechanism research revealed that hsa_circ_0001610 functioned as the competing endogenous RNA of miR-139-5p, thereby upregulating cyclin B1 expression, which is a vital pusher of radioresistance in several types of cancer by regulating the cell cycle. Hsa_circ_0001610 overexpression reduced the radiosensitivity of EC cells, which was then reversed by miR-139-5p overexpression. In vivo, the promotion effect of EXOs on xenograft tumor growth in nude mice treated with irradiation was further reinforced after hsa_circ_0001610 overexpression. In conclusion, TAM-derived exosomes transferred hsa_circ_0001610 to EC cells, and the overexpressed hsa_circ_0001610 in EC cells released cyclin B1 expression through adsorbing miR-139-5p, thereby weakening the radiosensitivity of EC cells.

The incidence of colon cancer has shown an upward trend in recent years, and the appearance of colon polyps is one of the signs of colon cancer. The detection and segmentation of colon polyps are one of the doctors' auxiliary diagnostic methods. However, the increasing number of model parameters and inference memory requirements make the engineering of polyp segmentation models a challenging task. In this paper, an efficient polyp segmentation model based on Unet and RNNPool named RP-Unet is proposed. The first two blocks consisted of two convolutional and max pooling layers in Unet are replaced with the proposed RNNPool Down and Fuse (RDF) modules to rapidly downsample and fuse the input feature maps, and they also provide feature maps for skip connection. The last two blocks in the encoder are replaced with the proposed Double Convolution with Residual connection and RNNPool (DCRR) modules, in which the convolution layers are residually connected, and the max pooling layer is replaced directly with RNNPool. In the two proposed modules, up mapping and channel mapping are used to strengthen feature propagation by mapping activation maps logically instead of allocating unnecessary memory. The proposed RP-Unet is evaluated on two polyp segmentation datasets, and experiments show that the peak inference memory is reduced by almost 22%, while the segmentation accuracy is not significantly reduced.

Premature birth is associated with a high prevalence of neurodevelopmental impairments in surviving infants. The hippocampus is known to be critical for learning and memory, yet the putative effects of hippocampal dysfunction remain poorly understood in preterm neonates. In particular, while asymmetry of the hippocampus has been well noted both structurally and functionally, how preterm birth impairs hippocampal development and to what extent the hippocampus is asymmetrically impaired by preterm birth have not been well delineated. In this study, we compared volumetric growth and shape development in the hippocampal hemispheres and structural covariance (SC) between hippocampal vertices and cortical thickness in cerebral cortex regions between two groups. We found that premature infants had smaller volumes of the right hippocampi only. Lower thickness was observed in the hippocampal head in both hemispheres for preterm neonates compared with full-term peers, though preterm neonates exhibited an accelerated age-related change of hippocampal thickness in the left hippocampi. The SC between the left hippocampi and the limbic lobe of the premature infants was severely impaired compared with the term-born neonates. These findings suggested that the development of the hippocampus during the third trimester may be altered following early extrauterine exposure with a high degree of asymmetry.

Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Background Integrin-mediated platelet-tumor cell contacting plays an important role in promoting epithelial-mesenchymal transition (EMT) transformation of tumor cells and cancer metastasis, but whether it occurs in breast cancer cells is not completely clear. Objective The purpose of this study was to investigate the role of integrin α2β1 in platelet contacting to human breast cancer cell line MCF-7 and its effect on the EMT and the invasion of MCF-7 cells. Methods Human platelets were activated by thrombin, and separated into pellets and releasates before the co-incubation with MCF-7 cells. Cell invasion was evaluated by transwell assay. The surface integrins on pellets and MCF-7 cells were inhibited by antibodies. The effect of integrin α2β1 on Wnt-β-catenin pathway was assessed by integrin α2β1-silencing and Wnt-β-catenin inhibitor XAV. The therapeutic effect of integrin α2β1-silencing was confirmed in the xenograft mouse model. Results Pellets promote the invasion and EMT of MCF-7 cells via direct contacting of surface integrin α2β1. The integrin α2β1 contacting activates Wnt-β-catenin pathway and promotes the expression of EMT proteins in MCF-7 cells. The activated Wnt-β-catenin pathway also promotes the autocrine of TGF-β1 in MCF-7 cells. Both Wnt-β-catenin and TGF-β1/pSmad3 pathways promote the expression of EMT proteins. Integrin α2β1-silencing inhibits breast cancer metastasis in vivo. Conclusions The direct interaction between platelets and tumor cells exerts its pro-metastatic function via surface integrin α2β1 contacting and Wnt-β-catenin activation. Integrin α2β1-silencing has the potential effect of inhibiting breast cancer metastasis.

Objectives The lenticulostriate arteries (LSAs) with small diameters of a few hundred microns take origin directly from the high flow middle cerebral artery (MCA), making them especially susceptible to damage (e.g. by hypertension). This study aims to present high resolution (isotropic ∼0.5 mm), black blood MRI for the visualization and characterization of LSAs at both 3 T and 7 T. Materials and methods T1-weighted 3D turbo spin-echo with variable flip angles (T1w TSE-VFA) sequences were optimized for the visualization of LSAs by performing extended phase graph (EPG) simulations. Twenty healthy volunteers (15 under 35 years old, 5 over 60 years old) were imaged with the T1w TSE-VFA sequences at both 3 T and 7 T. Contrast-to-noise ratio (CNR) was quantified, and LSAs were manually segmented using ITK-SNAP. Automated Reeb graph shape analysis was performed to extract features including vessel length and tortuosity. All quantitative metrics were compared between the two field strengths and two age groups using ANOVA. Results LSAs can be clearly delineated using optimized 3D T1w TSE-VFA at 3 T and 7 T, and a greater number of LSA branches can be detected compared to those by time-of-flight MR angiography (TOF MRA) at 7 T. The CNR of LSAs was comparable between 7 T and 3 T. T1w TSE-VFA showed significantly higher CNR than TOF MRA at the stem portion of the LSAs branching off the medial middle cerebral artery. The mean vessel length and tortuosity were greater on TOF MRA compared to TSE-VFA. The number of detected LSAs by both TSE-VFA and TOF MRA was significantly reduced in aged subjects, while the mean vessel length measured on 7 T TSE-VFA showed significant difference between the two age groups. Conclusion The high-resolution black-blood 3D T1w TSE-VFA sequence offers a new method for the visualization and quantification of LSAs at both 3 T and 7 T, which may be applied for a number of pathological conditions related to the damage of LSAs.