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.

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.

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.

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.

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.

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.

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.

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.

Factors influencing the choice of endotracheal intubation and mechanical ventilation in patients with acute respiratory distress syndrome caused by viral pneumonia / 中华危重病急救医学

Objective:To investigate the influencing factors of endotracheal intubation and mechanical ventilation (ETI-MV) in patients with acute respiratory distress syndrome (ARDS) caused by viral pneumonia, and to provide evidence for individualized use of ETI-MV.Methods:Patients with ARDS due to viral pneumonia admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed from November 2017 to March 2022. The gender, age, concomitant diseases, clinical symptoms and signs, complications, lab results, ARDS severity, infectious virus type, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), respiratory support methods and prognosis-related variables were collected. Univariate analysis was performed on each factor, and the variables with statistical significance in the univariate analysis were subjected multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each index for the implementation of ETI-MV.Results:A total of 117 patients were enrolled in the study, including 61 patients in the ETI-MV group, and 3 patients (4.9%), 39 patients (63.9%) and 19 patients (31.1%) with mild, moderate and severe ARDS, respectively. There were 56 patients in non-ETI-MV group, and the mild, moderate and severe ARDS cases were 16 cases (28.6%), 38 cases (67.8%) and 2 cases (3.6%), respectively. There was significant difference between the two groups ( P < 0.05). Univariate analysis showed that during 24 hours admitted to RICU, the levels of interleukin-6 [IL-6 (ng/L): 104.0±90.0 vs. 62.4±76.0], oxygenation index [PaO 2/FiO 2 (mmHg, 1 mmHg≈0.133 kPa): 123.9±30.9 vs. 173.6±28.5], the proportion of cases with pulmonary infiltrating opacity distribution range ≥ 3/4 lung fields [85.3% (52/61) vs. 21.5% (12/56)], APACHE Ⅱ score ≥ 16.5 [67.2% (41/61) vs. 42.9% (24/56)], the rate of nosocomial invasive aspergillus infection [14.8% (9/61) vs. 3.6% (2/56)], the percentage of nosocomial bacterial infection [16.4% (10/61) vs. 3.6% (2/56)], and the lowest CD4 + T lymphocyte count in the course of the disease [cells/mm 3: 192.2±35.8 vs. 215.0±58.3] had significant differences between ETI-MV and non-ETI-MV group (all P < 0.05). Multivariate Logistic regression analysis showed that during 24 hours admitted to RICU the distribution range of pulmonary infiltrating opacity ≥ 3/4 the lung fields [odds ratio ( OR) = 12.527, 95% confidence interval (95% CI) = 3.279-47.859, P < 0.001], APACHE Ⅱ score ≥ 16.5 ( OR = 30.604, 95% CI = 4.318-216.932, P = 0.001), PaO 2/FiO 2 ( OR = 0.948, 95% CI = 0.925-0.972, P < 0.001), CD4 + T lymphocytes cell count ( OR = 0.975, 95% CI = 0.955-0.995, P = 0.015), and nosocomial bacterial infection ( OR = 38.338, 95% CI = 1.638-897.158, P = 0.023) were independent risk factors for ETI-MV. The area under the ROC curve (AUC) of ROC showed that PaO 2/FiO 2 had the greatest predictive value for ETI-MV, with AUC of 0.903, sensitivity of 91.1% and specificity of 95.1% in case of cutoff value of 151 mmHg. The AUC of pulmonary infiltrating opacity distribution range was 0.809, the sensitivity of 85.2%, specificity of 78.6% when the cutoff value was ≥ 3/4 lung field. APACHE Ⅱ scores had the lowest predictive value for selecting ETI-MV, with AUC of 0.704, sensitivity of 83.6% and specificity of 57.1% under the cutoff value was 16.5. Conclusions:For patients with ARDS caused by viral pneumonia, PaO 2/FiO 2 is still the classic reference for selecting ETI-MV, however, the distribution range of pulmonary infiltrating opacity and the systemic severity of the disease during 24 hours admitted to the RICU may provide supplemental helpful information to determine whether the patients choose ETI-MV, especially for moderate ARDS.

Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.

Neuroblastoma is the commonest extracranial pediatric malignancy. With few recurrent single nucleotide variations (SNVs), mutation-based precision oncology approaches have limited utility, but its frequent and heterogenous copy number variations (CNVs) could represent genomic dependencies that may be exploited for personalized therapy. Patient-derived cell culture (PDC) models can facilitate rapid testing of multiple agents to determine such individualized drug-responses. Thus, to study the relationship between individual genomic aberrations and therapeutic susceptibilities, we integrated comprehensive genomic profiling of neuroblastoma tumors with drug screening of corresponding PDCs against 418 targeted inhibitors. We quantified the strength of association between copy number and cytotoxicity, and validated significantly correlated gene-drug pairs in public data and using machine learning models. Somatic mutations were infrequent (3.1 per case), but copy number losses in 1p (31%) and 11q (38%), and gains in 17q (69%) were prevalent. Critically, in-vitro cytotoxicity significantly correlated only with CNVs, but not SNVs. Among 1278 significantly correlated gene-drug pairs, copy number of GNA13 and DNA damage response genes CBL, DNMT3A, and PPM1D were most significantly correlated with cytotoxicity; the drugs most commonly associated with these genes were PI3K/mTOR inhibitor PIK-75, and CDK inhibitors P276-00, SNS-032, AT7519, flavopiridol and dinaciclib. Predictive Markov random field models constructed from CNVs alone recapitulated the true z-score-weighted associations, with the strongest gene-drug functional interactions in subnetworks involving PI3K and JAK-STAT pathways. Together, our data defined individualized dose-dependent relationships between copy number gains of PI3K and STAT family genes particularly on 17q and susceptibility to PI3K and cell cycle agents in neuroblastoma. Integration of genomic profiling and drug screening of patient-derived models of neuroblastoma can quantitatively define copy number-dependent sensitivities to targeted inhibitors, which can guide personalized therapy for such mutationally quiet cancers.

Incorporating Robustness to Imaging Physics into Radiomic Feature Selection for Breast Cancer Risk Estimation.

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns-a woman's left and right breasts. From 341 features, we identified "robust" features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

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.

Fluorescence-based screening for engineered aldo-keto reductase KmAKR with improved catalytic performance and extended substrate scope.

BACKGROUND: Aldo-keto reductases-catalyzed transformations of ketones to chiral alcohols have become an established biocatalytic process step in the pharmaceutical industry. Previously, we have discovered an aldo-keto reductase (AKR) from Kluyveromyces marxianus that is active to the aliphatic tert-butyl 6-substituted (5R/S)-hydroxy-3-oxohexanoates, but it is inactive to aromatic ketones. In order to acquire an excellent KmAKRmutant for ensuring the simultaneous improvement of activity-thermostability toward tert-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate ((5R)-1) and broadening the universal application prospects toward more substrates covering both aliphatic and aromatic ketones, a fluorescence-based high-throughput (HT) screening technique was established. MAIN METHODS AND MAJOR RESULTS: The directed evolution of KmAKR variant M5 (KmAKR-W297H/Y296W/K29H/Y28A/T63M) produced the "best" variant M5-Q213A/T23V. It exhibited enhanced activity-thermostability toward (5R)-1, improved activity toward all 18 test substrates and strict R-stereoselectivity toward 10 substrates in comparison to M5. The enhancement of enzymatic activity and the extension of substrate scope covering aromatic ketones are proposed to be largely attributed to pushing the binding pocket of M5-Q213A/T23V to the enzyme surface, decreasing the steric hindrance at the entrance and enhancing the flexibility of loops surrounding the active center. In addition, combined with 0.94 g dry cell weight (DCW) L-1 glucose dehydrogenase from Exiguobacterium sibiricum (EsGDH) for NADPH regeneration, 2.81 g DCW L-1 M5-Q213A/T23V completely converted (5R)-1 of up to 450 g L-1 at 120 g g-1 substrates/catalysts (S/C), yielding the corresponding optically pure tert-butyl 6-cyano-(3R,5R)-dihydroxyhexanoate ((3R,5R)-2, > 99.5% d.e.p ) with a space-time yield (STY) of 1.08 kg L-1 day-1 . CONCLUSIONS: A fluorescence-based HT screening system was developed to tailor KmAKR's activity, thermostability and substrate scope. The "best" variant M5-Q213A/T23V holds great potential application for the synthesis of aliphatic/aromatic R-configuration alcohols.

[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.

Fully automatic quantification of fibroglandular tissue and background parenchymal enhancement with accurate implementation for axial and sagittal breast MRI protocols.

PURPOSE: To propose and evaluate a fully automated technique for quantification of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) in breast MRI. METHODS: We propose a fully automated method, where after preprocessing, FGT is segmented in T1-weighted, nonfat-saturated MRI. Incorporating an anatomy-driven prior probability for FGT and robust texture descriptors against intensity variations, our method effectively addresses major image processing challenges, including wide variations in breast anatomy and FGT appearance among individuals. Our framework then propagates this segmentation to dynamic contrast-enhanced (DCE)-MRI to quantify BPE within the segmented FGT regions. Axial and sagittal image data from 40 cancer-unaffected women were used to evaluate our proposed method vs a manually annotated reference standard. RESULTS: High spatial correspondence was observed between the automatic and manual FGT segmentation (mean Dice similarity coefficient 81.14%). The FGT and BPE quantifications (denoted FGT% and BPE%) indicated high correlation (Pearson's r = 0.99 for both) between automatic and manual segmentations. Furthermore, the differences between the FGT% and BPE% quantified using automatic and manual segmentations were low (mean differences: -0.66 ± 2.91% for FGT% and -0.17 ± 1.03% for BPE%). When correlated with qualitative clinical BI-RADS ratings, the correlation coefficient for FGT% was still high (Spearman's ρ = 0.92), whereas that for BPE was lower (ρ = 0.65). Our proposed approach also performed significantly better than a previously validated method for sagittal breast MRI. CONCLUSIONS: Our method demonstrated accurate fully automated quantification of FGT and BPE in both sagittal and axial breast MRI. Our results also suggested the complexity of BPE assessment, demonstrating relatively low correlation between segmentation and clinical rating.

Relationship between monocyte/lymphocyte ratio and non-culprit plaque vulnerability in patients with acute coronary syndrome: An optical coherence tomography study.

The importance of monocyte/lymphocyte ratio (MLR) has been indicated in the initiation and progression of coronary artery disease. However, few previous researches demonstrated the relationship between MLR and plaque vulnerability. We aimed to investigate coronary non-culprit plaque vulnerability in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT).A total of 72 ACS patients who underwent coronary angiography and OCT test in Beijing Anzhen Hospital were included in this retrospective study. The plaque vulnerability and plaque morphology were assessed by OCT.The non-culprit plaque in high MLR group exhibited more vulnerable features, characterizing as thinner thickness of fibrous cap (P = .013), greater maximum lipid core angle (P = .010) and longer lipid plaque length (P = .041). A prominently negative liner relation was found between MLR and thickness of fibrous cap (R = -0.225, P = .005). Meanwhile, the proportion of OCT-detected thin cap fibro-atheroma (TCFA) (P = .014) and plaque rupture (P = .017) were higher in high MLR group. Most importantly, multivariable logistic regression analysis showed MLR level was identified as an independent contributor to the presence of TCFA (OR:3.316, 95%: 1.448-7.593, P = .005). MLR could differentiate TCFA with a sensitivity of 60.0% and a specificity of 85.1%.Circulating MLR level has potential value in identifying the presence of vulnerable plaque in patients with ACS. MLR, as a non- invasive biomarker of inflammation, may be valuable in revealing plaque vulnerability.

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.

Comparison of articaine, lidocaine and mepivacaine for buccal infiltration after inferior alveolar nerve block in mandibular posterior teeth with irreversible pulpitis.

Aims To compare the anaesthetic efficacy of articaine, lidocaine and mepivacaine for buccal infiltration (BI) following lidocaine inferior alveolar nerve block (IANB) in mandibular posterior teeth with irreversible pulpitis.Materials and methods Patients with irreversible pulpitis in mandibular posterior teeth and unsuccessful IANB were randomly assigned to three groups: articaine group (n = 52), lidocaine group (n = 52) and mepivacaine group (n = 52). They were instructed to rate the pain experienced at four phases (before the injection, after IANB, after BI and during endodontic access) on a Heft-Parker visual analogue scale (VAS). Success was defined as the ability to access and instrument the tooth with no pain or mild pain (VAS rating ≤54 mm) after BI.Results Multivariate logistic regression analysis showed that articaine was associated with a higher success rate compared with lidocaine (OR = 3.89, 95% CI: 1.35-11.27; P = 0.02) and mepivacaine (OR = 3.67, 95% CI: 1.24-9.75; P = 0.01), after controlling for age, gender and initial pain. VAS ratings were significantly lower in the articaine group compared with those in the lidocaine group and mepivacaine group after BI and during endodontic access (P <0.01).Conclusion Articaine as a supplemental BI following IANB is a more successful anaesthetic agent in mandibular posterior teeth with irreversible pulpitis compared with lidocaine and mepivacaine.

Calculation of Radiomic Features to Validate the Textural Realism of Physical Anthropomorphic Phantoms for Digital Mammography.

In this paper, radiomic features are used to validate the textural realism of two anthropomorphic phantoms for digital mammography. One phantom was based off a computational breast model; it was 3D printed by CIRS (Computerized Imaging Reference Systems, Inc., Norfolk, VA) under license from the University of Pennsylvania. We investigate how the textural realism of this phantom compares against a phantom derived from an actual patient's mammogram ("Rachel", Gammex 169, Madison, WI). Images of each phantom were acquired at three kV in 1 kV increments using auto-time technique settings. Acquisitions at each technique setting were repeated twice, resulting in six images per phantom. In the raw ("FOR PROCESSING") images, 341 features were calculated; i.e., gray-level histogram, co-occurrence, run length, fractal dimension, Gabor Wavelet, local binary pattern, Laws, and co-occurrence Laws features. Features were also calculated in a negative screening population. For each feature, the middle 95% of the clinical distribution was used to evaluate the textural realism of each phantom. A feature was considered realistic if all six measurements in the phantom were within the middle 95% of the clinical distribution. Otherwise, a feature was considered unrealistic. More features were actually found to be realistic by this definition in the CIRS phantom (305 out of 341 features or 89.44%) than in the phantom derived from a specific patient's mammogram (261 out of 341 features or 76.54%). We conclude that the texture is realistic overall in both phantoms.

Robust Radiomic Feature Selection in Digital Mammography: Understanding the Effect of Imaging Acquisition Physics Using Phantom and Clinical Data Analysis.

Studies have shown that combining calculations of radiomic features with estimates of mammographic density results in an even better assessment of breast cancer risk than density alone. However, to ensure that risk assessment calculations are consistent across different imaging acquisition settings, it is important to identify features that are not overly sensitive to changes in these settings. In this study, digital mammography (DM) images of an anthropomorphic phantom ("Rachel", Gammex 169, Madison, WI) were acquired at various technique settings. We varied kV and mAs, which control contrast and noise, respectively. DM images in women with negative screening exams were also analyzed. Radiomic features were calculated in the raw ("FOR PROCESSING") DM images; i.e., grey-level histogram, co-occurrence, run length, fractal dimension, Gabor Wavelet, local binary pattern, Laws, and co-occurrence Laws features. For each feature, the range of variation across technique settings in phantom images was calculated. This range was scaled against the range of variation in the clinical distribution (specifically, the range corresponding to the middle 90% of the distribution). In order for a radiomic feature to be considered robust, this metric of imaging acquisition variation (IAV) should be as small as possible (approaching zero). An IAV threshold of 0.25 was proposed for the purpose of this study. Out of 341 features, 284 features (83%) met the threshold IAV ≤ 0.25. In conclusion, we have developed a method to identify robust radiomic features in DM.