The long rod-shaped Sr2 MgSi2 O7 :Eu2+ ,Dy3+ with ultrahigh afterglow performance.

The afterglow properties of long afterglow luminescent materials are greatly affected by their defects, which are distributed on the grain surface. Increasing the exposed surface area is an important method to improve the afterglow performance. In this research, long rod-shaped long afterglow materials Sr2 MgSi2 O7 :Eu2+ ,Dy3+ were prepared using the hydrothermal-coprecipitation method. When the reaction time reached 96 h, the length of the afterglow materials could grow to 2 mm, and the sintering temperature was just 1150°C. The emission spectra of all obtained samples upon excitation at 397 nm had a maximum of 465 nm, which belonged to the representative transition of Eu2+ . The initial brightness was 1.35 cd/m2 . The afterglow time could reach 19 h, giving a good afterglow performance. The research on this kind of material has essential significance in the exploration of luminescence mechanisms and their applications.

High Dose Oestrogen in Life Threatening Obscure Gastrointestinal Bleeding.

Obscure gastrointestinal bleeding is defined as recurrent or persistent gastrointestinal bleeding in the setting of normal upper and lower endoscopies. There are reported use of numerous pharmacological agents to halt the bleeding, including oestrogen. We report a case of middle age gentleman with multiple comorbidities, presented with life threatening gastrointestinal bleeding. He underwent bidirectional endoscopies and mesenteric angiogram, but failed to localise the bleeding. Red blood cell scintigraphy showed numerous bleeding points in small and large bowels. A 5-day oral high dose oestrogen was prescribed in view of difficulty to manage the bleeding, in which the hemostasis was ultimately achieved.

Joint protection strategies for Saccharomyces boulardii: exogenous encapsulation and endogenous biofilm structure.

Biofilms are heterogeneous structures composed of microorganisms and the surrounding extracellular polymeric substances (EPS) that protect the microbial cells from harsh environments. Saccharomyces boulardii is the first yeast classified as a probiotic strain with unique properties. However, tolerance of S. boulardii biofilms to harsh environments especially during production and in the gastrointestine remains unknown. In this study, S. boulardii cells were encapsulated in alginate microcapsules and subsequently cultured to form biofilms, and their survival and tolerance were evaluated. Microencapsulation provided S. boulardii a confined space that enhanced biofilm formation. The thick alginate shell and the mature biofilm improved the ability of S. boulardii to survive under harsh conditions. The exogenous encapsulation and the endogenous biofilm structure together enhanced the gastrointestinal tolerance and thermotolerance of S. boulardii. Besides, as the alginate shell became thinner with an increase in the subsequent culture duration, the EPS of S. boulardii biofilms exerted an important protective effect in resisting high temperatures. The encapsulated biofilm of S. boulardii after 24-h culture exhibited 60 × higher thermotolerance at 60 °C (10 min), while those after 6-h and 24-h culture showed 1000 × to 550,000 × higher thermotolerance at 120 °C (1 min) compared with the planktonic cells without encapsulation. The present study's findings suggest that a combination of encapsulation and biofilm mode efficiently enhanced gastrointestinal tolerance and thermotolerance of S. boulardii. KEY POINTS: • Encapsulated S. boulardii in biofilm mode showed enhanced tolerance. • Exogenous shell and endogenous biofilm provided dual protection to S. boulardii.

[A Study of the Relationship Between Job Satisfaction and Work Engagement of Physicians in Public Hospitals].

OBJECTIVE: To understand the level of job satisfaction and work engagement of physicians in public hospitals, to analyze the interaction between job satisfaction and work engagement, and to discuss how each dimension of job satisfaction affects work engagement so as to provide information and reference for improving the level of work engagement of physicians in public hospitals. METHODS: Covering 6 public hospitals in Sichuan (3 tertiary-level hospitals and 3 secondary-level hospitals), 638 questionnaires were obtained from physicians through convenient sampling for data description and analysis. Pearson correlation method was used to analyze the correlation between job satisfaction and work engagement, and multiple linear stepwise regression method was used to analyze work engagement and the influencing factors of each dimension. RESULTS: With regard to job satisfaction, physicians showed high levels of satisfaction in personal safety (3.77±0.87), leadership identification and support (3.59±0.77), and job pressure (3.51±0.81). The mean points of work engagement and each dimension were as follows: total mean points of work engagement (4.02±0.99), dedication (4.21±1.13), absorption (4.19±1.08) and vigor (3.63±1.04). In job satisfaction, salary and benefits, work environment, social recognition, organizational management, leadership identification and support are positively correlated to work engagement and all dimensions. In job satisfaction, 5 dimensions, including social recognition, leadership recognition and support, work achievement, personal safety and organizational management, had a significant influence on work engagement and all dimensions. CONCLUSION: Emphasis on the high-level needs for recognition and self-actualization of doctors, doctor-patient communication, and personal development of doctors may improve doctors' job satisfaction and work engagement.

Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response.

Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient-derived cell cultures (PDCs) from chemo-naïve and post-treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo-response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal-type gene expression signature and showed upregulation of pro-angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard-of-care cytotoxics at human Cmax -equivalent concentrations, MYCN-amplified and non-MYCN-amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients' responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept study, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug-response testing.

Clinical, pathological and loss of heterozygosity differences in Wilms tumors between Asian and non-Asian children.

Wilms tumor demonstrates significant interethnic epidemiological, histological and outcome differences, and is rare and poorly studied among Asians. We compared the clinicopathological, and loss of heterozygosity (LOH) profile and survival outcomes of Asian and non-Asian patients with Wilms tumor. Clinical charts and histological slides from patients with malignant renal tumors over a period of 20 years were retrospectively reviewed. We adapted a genotyping assay to determine 1p36 and 16q21-22 LOH in formalin-fixed paraffin-embedded (FFPE) specimens, and compared these characteristics between Asian and non-Asian patients. Fifty-three (79.1%) Asian and 14 (20.9%) non-Asian patients had Wilms tumors. Compared to non-Asians, Asians were younger (mean 4.6 and 4.0 years, respectively), had more equal gender distribution (female: male = 1.8 and 1.0, respectively), fewer tumors with unfavorable histology (25.0% and 4.1%, respectively, p = 0.05), and less advanced disease at presentation, yet similar nodal metastases rates (16.7% and 18.4%, respectively). No Asian patients had bilateral tumors. Our adapted genotyping assay accurately determined LOH in FFPE specimens <10 years post-fixation. Among 30 Asian patients, 1p and 16q LOH were each detected in 5 (16.7%) patients, respectively-similar to rates reported in other ethnicities. Yet after similar treatment with National Wilms Tumor Study regimens, 15-year event-free and overall survival for Asian patients was 95.7% and 96.3% respectively. In summary, despite similar nodal metastasis and LOH rates, Asian patients had fewer unfavorable histology tumors, lower-stage disease, and better survival outcomes. The bases for these differences and implications on treatment strategy for these patients warrant further study.

Radiomic Phenotypes of Mammographic Parenchymal Complexity: Toward Augmenting Breast Density in Breast Cancer Risk Assessment.

Purpose To identify phenotypes of mammographic parenchymal complexity by using radiomic features and to evaluate their associations with breast density and other breast cancer risk factors. Materials and Methods Computerized image analysis was used to quantify breast density and extract parenchymal texture features in a cross-sectional sample of women screened with digital mammography from September 1, 2012, to February 28, 2013 (n = 2029; age range, 35-75 years; mean age, 55.9 years). Unsupervised clustering was applied to identify and reproduce phenotypes of parenchymal complexity in separate training (n = 1339) and test sets (n = 690). Differences across phenotypes by age, body mass index, breast density, and estimated breast cancer risk were assessed by using Fisher exact, χ2, and Kruskal-Wallis tests. Conditional logistic regression was used to evaluate preliminary associations between the detected phenotypes and breast cancer in an independent case-control sample (76 women diagnosed with breast cancer and 158 control participants) matched on age. Results Unsupervised clustering in the screening sample identified four phenotypes with increasing parenchymal complexity that were reproducible between training and test sets (P = .001). Breast density was not strongly correlated with phenotype category (R2 = 0.24 for linear trend). The low- to intermediate-complexity phenotype (prevalence, 390 of 2029 [19%]) had the lowest proportion of dense breasts (eight of 390 [2.1%]), whereas similar proportions were observed across other phenotypes (from 140 of 291 [48.1%] in the high-complexity phenotype to 275 of 511 [53.8%] in the low-complexity phenotype). In the independent case-control sample, phenotypes showed a significant association with breast cancer (P = .001), resulting in higher discriminatory capacity when added to a model with breast density and body mass index (area under the curve, 0.84 vs 0.80; P = .03 for comparison). Conclusion Radiomic phenotypes capture mammographic parenchymal complexity beyond conventional breast density measures and established breast cancer risk factors. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Pinker in this issue.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Mammographic breast density decreases after bariatric surgery.

PURPOSE: Breast density (BD), an important risk factor for breast cancer, can change over time in some women, but the underlying mechanism is unclear. Very little is known about the impact of surgical weight loss on BD. Our hypothesis is that weight loss after bariatric surgery is associated with a significant and favorable change in mammographic BD. METHODS: We identified 1097 women 40 years of age or older who underwent gastric bypass or sleeve gastrectomy at our institution from 2010 to 2014. Women who did not have either pre- and post-bariatric surgery mammograms performed at our institution were excluded; 110 had both mammograms and comprised the cohort. Breast density was determined both qualitatively, using reported BI-RADS density, and quantitatively, using the Laboratory for Individualized Breast Radiodensity Assessment. RESULTS: Qualitative BI-RADS density, quantitative breast area, and percent BD significantly decreased in post-bariatric surgery mammograms (p = 0.009, <0.001, and <0.001, respectively). CONCLUSIONS: Our retrospective study demonstrated that surgical weight loss was associated with a significant decrease in breast density. Additional studies are warranted to validate our findings and elucidate the molecular mechanisms underlying breast density change after weight loss surgery.

Capturing heterogeneous group differences using mixture-of-experts: Application to a study of aging.

In MRI studies, linear multi-variate methods are often employed to identify regions or connections that are affected due to disease or normal aging. Such linear models inherently assume that there is a single, homogeneous abnormality pattern that is present in all affected individuals. While kernel-based methods can implicitly model a non-linear effect, and therefore the heterogeneity in the affected group, extracting and interpreting information about affected regions is difficult. In this paper, we present a method that explicitly models and captures heterogeneous patterns of change in the affected group relative to a reference group of controls. For this purpose, we use the Mixture-of-Experts (MOE) framework, which combines unsupervised modeling of mixtures of distributions with supervised learning of classifiers. MOE approximates the non-linear boundary between the two groups with a piece-wise linear boundary, thus allowing discovery of multiple patterns of group differences. In the case of patient/control comparisons, each such pattern aims to capture a different dimension of a disease, and hence to identify patient subgroups. We validated our model using multiple simulation scenarios and performance measures. We applied this method to resting state functional MRI data from the Baltimore Longitudinal Study of Aging, to investigate heterogeneous effects of aging on brain function in cognitively normal older adults (>85years) relative to a reference group of normal young to middle-aged adults (<60years). We found strong evidence for the presence of two subgroups of older adults, with similar age distributions in each subgroup, but different connectivity patterns associated with aging. While both older subgroups showed reduced functional connectivity in the Default Mode Network (DMN), increases in functional connectivity within the pre-frontal cortex as well as the bilateral insula were observed only for one of the two subgroups. Interestingly, the subgroup showing this increased connectivity (unlike the other subgroup) was, cognitively similar at baseline to the young and middle-aged subjects in two of seven cognitive domains, and had a faster rate of cognitive decline in one of seven domains. These results suggest that older individuals whose baseline cognitive performance is comparable to that of younger individuals recruit their "cognitive reserve" later in life, to compensate for reduced connectivity in other brain regions.

Deformable registration for quantifying longitudinal tumor changes during neoadjuvant chemotherapy.

PURPOSE: To evaluate DRAMMS, an attribute-based deformable registration algorithm, compared to other intensity-based algorithms, for longitudinal breast MRI registration, and to show its applicability in quantifying tumor changes over the course of neoadjuvant chemotherapy. METHODS: Breast magnetic resonance images from 14 women undergoing neoadjuvant chemotherapy were analyzed. The accuracy of DRAMMS versus five intensity-based deformable registration methods was evaluated based on 2,380 landmarks independently annotated by two experts, for the entire image volume, different image subregions, and patient subgroups. The registration method with the smallest landmark error was used to quantify tumor changes, by calculating the Jacobian determinant maps of the registration deformation. RESULTS: DRAMMS had the smallest landmark errors (6.05 ± 4.86 mm), followed by the intensity-based methods CC-FFD (8.07 ± 3.86 mm), NMI-FFD (8.21 ± 3.81 mm), SSD-FFD (9.46 ± 4.55 mm), Demons (10.76 ± 6.01 mm), and Diffeomorphic Demons (10.82 ± 6.11 mm). Results show that registration accuracy also depends on tumor versus normal tissue regions and different patient subgroups. CONCLUSIONS: The DRAMMS deformable registration method, driven by attribute-matching and mutual-saliency, can register longitudinal breast magnetic resonance images with a higher accuracy than several intensity-matching methods included in this article. As such, it could be valuable for more accurately quantifying heterogeneous tumor changes as a marker of response to treatment.

Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.

Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.

Clinicopathological and treatment response characteristics of updated rhabdomyosarcoma histomolecular subtypes: An Asian population-based study.

AIM: New histomolecular subtypes of rhabdomyosarcoma have recently been defined but their corresponding clinical characteristics are not well described. Also, these clinical phenotypes vary greatly by age and ethnicity but have not been profiled in Asian populations. Thus, we sought to determine the landscape of rhabdomyosarcoma subtypes in a national Asian cohort and compare clinical characteristics among age groups and molecular subtypes. METHODS: We performed a retrospective population-based study of all rhabdomyosarcoma patients in Singapore public hospitals from 2004 to 2014 (n = 67), and assigned histomolecular subtypes according to the updated 2020 WHO classification of soft tissue tumors following central pathology review and molecular profiling. RESULTS: Age-specific prevalence followed a tri-modal peak. There were significantly more embryonal and alveolar (p = 0.032) and genitourinary (non-bladder/prostate) tumors (p = 0.033) among children. Older age was associated with complete resection among spindle cell/sclerosing tumors (p = 0.027), with the omission of chemotherapy among embryonal tumors (p = 0.001), and with poorer survival among embryonal and alveolar tumors (p = 0.026, p = 0.022, respectively). Overall survival differed with stage, group, and surgical resection, adjusted for age group (p = 0.004, p = 0.001, p = 0.004, respectively). Spindle-cell/sclerosing tumors showed an indolent phenotype with a significantly lower incidence of nodal metastasis (p = 0.002), but two of 15 patients with MYOD1 mutations had a contrastingly aggressive disease. CONCLUSION: Disease and treatment response profiles of rhabdomyosarcoma subtypes vary significantly between adults and children, especially surgical resectability. In our Asian population, poorer outcomes were observed in adults with embryonal and alveolar tumors, while activating mutations influence the behavior of otherwise favorable spindle cell/sclerosing tumors.

(5-Bromo-2-hy-droxy-phen-yl)(4-propyl-cyclo-hex-yl)methanone.

In the title compound, C(16)H(21)BrO(2), the cyclo-hexane ring adopts a chair conformation. The hy-droxy and carbonyl groups are involved in an intra-molecular O-H⋯O hydrogen bond. In the crystal, weak C-H⋯O inter-actions link the mol-ecules into zigzag chains along [010].

Enhanced Lateral Photovoltaic Effects in n-Si/SiO2/PEDOT:PSS Structures.

Organic/silicon hybrid structures have been extensively studied for the application of solar cells due to their high photoelectric conversion efficiency and simple fabrication process. However, studies of lateral photovoltaic effects (LPEs) in the devices are still scarce. Herein, the Si/SiO2/PEDOT:PSS devices were prepared by spin-coating, and showing the lateral photovoltage (LPV) sensitivity of 14.0 mV/mm at room temperature, which is higher than the control samples of Si/SiO2 (0.1 mV/mm) and Si/PEDOT:PSS (9.0 mV/mm) structures. With the decrease in temperature, the lateral photovoltage increases initially, and reaches a peak at around 210 K, then drops accordingly. The enhancement of LPE can be mainly ascribed to the formation of the p-n junction and the native oxide layer at the organic/inorganic interface.

Atomic force microscopy application to study of the biomechanical properties of the aortic intima in the context of early atherosclerosis.

Atherosclerosis is characterized by the infiltration of macrophages, accumulation of lipids, activation of endothelial cells and synthesis of extracellular matrix by vascular smooth muscle cells. However, there have been few atomic force microscopy (AFM) studies of the aortic intima in situ in the context of atherosclerosis. By employing a customized liquid cell for AFM, we investigated the aortic intima obtained from male C57BL/6 ApoE-deficient mice (ApoE-/- ) aged 14 weeks and male C57BL/6 ApoE-sufficient mice (ApoE+/+ ) aged between 18 and 26 weeks that were fed a high-fat and high-cholesterol diet for 4 weeks and performed force spectroscopy mapping of the biomechanical properties of the intima. In the aortas of ApoE-deficient mice, the intima became stiffer than that of ApoE-sufficient mice. In addition, the cytoskeleton of endothelial cells was enlarged, and extracellular matrix accumulated. The biomechanical properties of the aortic intima are altered in early atherogenesis, which may be induced by the enlargement of the endothelial cell cytoskeleton and the increased synthesis of extracellular matrix by activated smooth muscle cells.

Rhizosphere and Straw Return Interactively Shape Rhizosphere Bacterial Community Composition and Nitrogen Cycling in Paddy Soil.

Currently, how rice roots interact with straw return in structuring rhizosphere communities and nitrogen (N) cycling functions is relatively unexplored. In this study, paddy soil was amended with wheat straw at 1 and 2% w/w and used for rice growth. The effects of the rhizosphere, straw, and their interaction on soil bacterial community composition and N-cycling gene abundances were assessed at the rice maturity stage. For the soil without straw addition, rice growth, i.e., the rhizosphere effect, significantly altered the bacterial community composition and abundances of N-cycling genes, such as archaeal and bacterial amoA (AOA and AOB), nirK, and nosZ. The comparison of bulk soils between control and straw treatments showed a shift in bacterial community composition and decreased abundance of AOA, AOB, nirS, and nosZ, which were attributed to sole straw effects. The comparison of rhizosphere soils between control and straw treatments showed an increase in the nifH gene and a decrease in the nirK gene, which were attributed to the interaction of straw and the rhizosphere. The number of differentially abundant genera in bulk soils between control and straw treatments was 13-23, similar to the number of 16-22 genera in rhizosphere soil between control and straw treatment. However, the number of genera affected by the rhizosphere effect was much lower in soil amended with straw (3-4) than in soil without straw addition (9). Results suggest possibly more pronounced impacts of straw amendments in shaping soil bacterial community composition.

Pro-metastatic and mesenchymal gene expression signatures characterize circulating tumor cells of neuroblastoma patients with bone marrow metastases and relapse.

Existing marker-based methods of minimal residual disease (MRD) determination in neuroblastoma do not effectively enrich for the circulating disease cell population. Given the relative size differential of neuroblastoma tumor cells over normal hematogenous cells, we hypothesized that cell size-based separation could enrich circulating tumor cells (CTCs) from blood samples and disseminated tumor cells (DTCs) from bone marrow aspirates (BMA) of neuroblastoma patients, and that their gene expression profiles could vary dynamically with various disease states over the course of treatment. Using a spiral microfluidic chip, peripheral blood of 17 neuroblastoma patients at 3 serial treatment timepoints (diagnosis, n=17; post-chemotherapy, n=11; and relapse, n=3), and bone marrow samples at diagnosis were enriched for large intact circulating cells. Profiling the resulting enriched samples with immunohistochemistry and mRNA expression of 1490 cancer-related genes via NanoString, 13 of 17 samples contained CTCs displaying cytologic atypia, TH and PHOX2B expression and/or upregulation of cancer-associated genes. Gene signatures reflecting pro-metastatic processes and the neuroblastoma mesenchymal super-enhancer state were consistently upregulated in 7 of 13 samples, 6 of which also had metastatic high-risk disease. Expression of 8 genes associated with PI3K and GCPR signaling were significantly upregulated in CTCs of patients with bone marrow metastases versus patients without. Correspondingly, in patients with marrow metastases, differentially-expressed gene signatures reflected upregulation of immune regulation in bone marrow DTCs versus paired CTCs samples. In patients who later developed disease relapse, 5 genes involved in immune cell regulation, JAK/STAT signaling and the neuroblastoma mesenchymal super-enhancer state (OLFML2B, STAT1, ARHGDIB, STAB1, TLR2) were upregulated in serial CTC samples over their disease course, despite urinary catecholamines and bone marrow aspirates not indicating the disease recurrences. In summary, using a label-free cell size-based separation method, we enriched and characterized intact circulating cells in peripheral blood indicative of neuroblastoma CTCs, as well as their DTC counterparts in the bone marrow. Expression profiles of pro-metastatic genes in CTCs correlated with the presence of bone marrow metastases at diagnosis, while longitudinal profiling identified persistently elevated expression of genes in CTCs that may serve as novel predictive markers of hematogenous MRD in neuroblastoma patients that subsequently relapse.

Graphene oxide based photoinduced charge transfer label-free near-infrared fluorescent biosensor for dopamine.

While the super fluorescence quenching capacity of graphene and graphene oxide (GO) has been extensively employed to develop fluorescent sensors, their own unique fluorescence and its potential for chemo-/biosensing have seldom been explored. Here we report a GO-based photoinduced charge transfer (PCT) label-free near-infrared (near-IR) fluorescent biosensor for dopamine (DA). The multiple noncovalent interactions between GO and DA and the ultrafast decay at the picosecond range of the near-IR fluorescence of GO resulted in effective self-assembly of DA molecules on the surface of GO, and significant fluorescence quenching, allowing development of a PCT-based biosensor with direct readout of the near-IR fluorescence of GO for selective and sensitive detection of DA. The developed method gave a detection limit of 94 nM and a relative standard deviation of 2.0% for 11 replicate detections of 2.0 µM DA and was successfully applied to the determination of DA in biological fluids with quantitative recovery (98-115%).

Bis(4-eth-oxy-phen-yl) sulfoxide.

In the title compound, C(16)H(18)O(3)S, the dihedral angle between the benzene rings is 82.7 (2)°. The O atom of the sulfoxide group is disordered over two orientations with refined occupancy factors of 0.563 (3):0.437 (3). In the crystal, mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds, forming chains along the b axis.