Une entérostomie double temporaire (ESDT) peut entraîner une insuffisance intestinale de type II (II2) et interrompre le cycle entéro-hépatique (CEH) des sels biliaires (SB). La réinstillation du chyme (RC) rétablit la continuité fonctionnelle de l’intestin. Les SB activent le récepteur de transcription nucléaire farnésoïde X (FXR) dans les entérocytes de l’iléon terminal. FXR stimule la sécrétion d’une entérokine, le fibroblast growth factor FGF19. Dans le foie, FGF19 freine la synthèse des sels biliaires par inhibition du 7α-OH-4-cholesten-3-one (C4). Le C4 plasmatique est un marqueur de la synthèse des SB. Démontrer que la RC est associée à une augmentation du FGF19 et à la baisse du C4 dans le plasma. Étude multicentrique prospective non interventionnelle non randomisée (ClinicalTrials.gov Identifier : NCT02990195) : CHU Rennes (promoteur), Clinique Saint Yves, Rennes (RC), Maastricht University Hospital, Pays Bas (biologie). Critères d’Inclusion : ESDT avec II2, éligible à la RC. Dosages plasmatiques avant (J-3 et J0, on retient la valeur moyenne (V0)) et pendant RC (J7, J21, J35, J49) : FGF19, C4 (chromatographie liquide-spectrométrie de masse (LC-MS)), SB totaux (enzymatic cycling method (Diazyme)), tests hépatiques, citrulline (LC-MS). Autres données : longueur du grêle d’aval (LGa), débit stomial avant RC, poids des selles pendant RC. Statistique : comparaison des moyennes appariées vs V0 (Test-t de Student), corrélations de Pearson. Patients inclus : 7H, 5F, 68 ± 15 ans, IMC 22,8 ± 4,7.Concentrations plasmatiques des marqueurs de la régulation de la sécrétion des SB.Empty CellV0 (n = 12)J7 (n = 11)J21 (n = 11)J35 (n = 10)T49FGF19 μg/L33,7 ± 25,5119 ± 79,2¥58 ± 38,2 ‡62,38 ± 38,767,4 ± 44,8 ‡C4 μg/L112,1 ± 98,421,1 ± 16,2 §41,7 ± 35,8 #11,4 ± 41,960,3 ± 78,7 ‡SB totaux μmol/L2,53 ± 1,791,18 ± 1,44 ‡1,22 ± 0,54 ¤1,41 ± 0,83‡1,64 ± 1,32 §¥ p < 0,005; # p < 0,01; § p < 0,025; ¤ p < 0,05; ‡ p > 0,05 Concentrations plasmatiques des marqueurs de la régulation de la sécrétion des SB. La baisse de C4 entre V0 et J7 est corrélée à l’augmentation du taux de FGF19 (r = −0,67, p = 0,024) et à l’augmentation de la citrullinémie (r = 0,70, p = 0,017. LGa (167 ± 81 cm) est corrélée avec les aires sous la courbe de C4 (r = −0,577), des SB totaux (r = −0,787 §) et de FGF19 (r = 0,539‡, p = 0,071). Amélioration des fonctions intestinales : réduction des pertes digestives 2237 ± 989 ml/24 h (stomie) vs 388 ± 645 g/24 h (selles), citrulline V0 = 21,5 ± 7,7 μmol/l vs J21 36,3 ± 18,8 μmol/l, p < 0,0015 à J7. Tests hépatiques (phosphatases alcalines 224 ± 97 vs 130 ± 42 (p = 0,004), γGT 197 ± 166 vs 51 ± 42 (p = 0,007). La RC augmente la concentration plasmatique de FGF19 suggérant une augmentation de la synthèse dans les iléocytes, associée à la baisse des concentrations de C4 et des SB totaux, donc à la réduction de la sécrétion hépatique des sels biliaires. Comme déjà démontré (Picot et al Clin Nutr 2010) la RC améliore la fonction intestinale.

Objective: Mental health condition of medical professionals in China is under-recognized. The current study aimed to determine the prevalence of depression and anxiety among healthcare professionals and explore the potential influence factors. Method: The study employed a cross-sectional design. All employees were surveyed in the first week of September 2017. General information included gender, age, workload, workplace violence, sleep quality and so on. Depression and anxiety were evaluated using PHQ-9 and GAD-7, respectively. SPSS 22.0 was used for data analysis. Logistic regression was conducted to explore risk factors contributed to metal health. Results: A total of 1,950 questionnaires were delivered, and 1,864 were returned with a response rate of 95.6%. The prevalence of depression and anxiety were 24.1% and 28.9%. As for workload, the average number of beds in charge per month is 65.97{+/-}95.58 beds, among which internal medicine department and surgical department endure more workloads. Though workers in ER and ICU manage fewer beds, they bear the longest nonstop working length in the previous month (19.18{+/-}10.82 h). There were 78.0% had suffered WPV in the preceding year. Staffs in ER and ICU are at higher risk to physical violence, especially doctors. Regarding to sleep quality, only 9.2% participants reported that they sleep well. Logistic regression indicated that workplace violence and sleep quality were independent risk factors for both anxiety and depression. Conclusion: The current study revealed the devastating conditions of mental disorders in medical workers and associated factors. Effective interventions are necessary to improve this situation.

The physician orders for external beam radiation therapy (EBRT) are associated with top-level treatment decision parameters including prescription dose, number of treatment fractions, treatment modality, treatment positioning, image guidance, etc. Physician order errors manifest as wrong values of individual parameters or logical inconsistencies between multiple parameters, which are difficult to detect even to human experts without going through many data and documentations. The purpose of this work is to investigate an association rule based approach to error detection in physician orders. The goal is to catch those errors earlier so to avoid the costly re-simulation and re-planning. Clinical physician orders for patients who received EBRT treatments from 2008 to 2017 at author’s institution. A total of 3059 individual single-prescription orders for nine disease sites – brain, breast, lung, pelvic, pelvis, prostate, spine, TBI, extremely – were acquired. Each order includes disease attributes and prescription parameters. Seven disease attributes were considered as conditions - site, tumor stage, nodal stage, metastatic stage, intent, laterality and previous treatment. Errors were detected on the four prescription parameters - total dose, fractions, technique and modality. The a priori algorithm was employed to extract frequent item sets from the historical physician orders. The association rules were generated by arranging items in each frequent item set as antecedent items and consequent items. The active association rules were selected according to their support and confident scores. The error detection tool raises an error flag if a new physician order breaks any active association rules. 10 percent of physician orders were randomly chosen and errors (wrong values in prescription parameters) were added manually for testing the performance of the method. A total of 257 active association rules were selected on average for each individual disease sites. The mean values of true positive and false positive rates of error detection were 92.38% and 10.23% respectively for single-prescription cases of nine disease sites. The wrong value of individual physician order parameters and logical inconsistence between physician order parameters could be detected by applying association rules with high positive rate, which could be further improved by optimizing the association rule discovery algorithm. The association rules are human expert understandable and verifiable, and linked directly to historical physician orders. Association rule discovery algorithm can naturally handle physician orders with missing values existing in more than 50% physician orders. The approach supports incorporation into independent error detection tools for assisting manual double-checks on physician orders. The success of the method here also gives promise to further scaling to include patient setup parameters and all treatment sites.

To expedite the contouring process for fast adaptive radiotherapy treatment planning, a deep densely connected convolutional neural network (DeepDenseNet) is proposed to automatically segment multiple organs, including liver, kidneys, stomach and large bowel from ViewRay 3D MR images. A densely connected convolutional neural network is proposed to segment liver, kidneys, stomach and large bowel from ViewRay 3D MR images voxel by voxel. A total of 120 patients' datasets were collected from our department for training and testing of the DeepDenseNet. Treatment sites of those 120 patients include pancreas, liver, stomach, adrenal gland and prostate. The DeepDenseNet was trained using 100 datasets and tested on the remaining 20 datasets. DICE coefficient, median Hausdorff distance (HD) and max HD were calculated for the 20 testing datasets to evaluate the segmentation accuracy of the DeepDenseNet. To demonstrate the clinical relevance and usefulness of the proposed method, the trained DeepDenseNet model was used to expedite the contouring process of adaptive treatment planning by segmenting these organs prior to manual contouring. For comparison, the time cost to contour these organs with and without the help of the DeepDenseNet was reported. The DeepDenseNet was able to segment the liver, kidney, large bowel and stomach with good accuracy and speed. For the 20 testing patients, the average DICE coefficients were 0.87, 0.88, 0.95 and 0.92 for large bowel, stomach, liver and kidneys respectively. The average median HD were 2.59 mm, 2.72 mm, 2.34 mm and 2.31 mm for large bowel, stomach, liver and kidneys respectively. Contouring experiments were performed by four medical physics residents. Three randomly selected patients' datasets were contoured by each resident. The experiments showed that the contouring process with the help of the DeepDenseNet was on average ×3.3 times faster than before. A new convolutional neural network called DeepDenseNet was proposed to segment multiple organs automatically from abdominal ViewRay 3D MR images with good segmentation accuracy and speed. The proposed method has the potential to greatly expedite the contouring process for fast adaptive radiotherapy treatment planning.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is negative for estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2). It is typically associated with high rate of metastasis and limited targeted treatment options. Chemotherapy is the standard treatment for metastatic TNBC. However, the development of chemoresistance limits its clinical application. Elevated expression of immune-related genes in TNBC suggests that immunotherapy strategies may provide new therapeutic options for TNBC. Programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been approved by the FDA for TNBC treatment. However, tumor immune evasion is considered an important obstacle. BRCA1 is a nuclear-cytoplasmic shuttling protein that plays a key role in preventing the development of a malignant phenotype. BRCA1 dysregulation and nuclear export are an important mechanism in cancer development and chemoresistance, especially in TNBC. Blocking BRCA1 nuclear export could be used as a strategy to prevent resistance. BRCA1 nuclear export has been reported to be mediated by several proteins such as BRCA1-binding protein 2 (BRAP2) and chromosomal maintenance 1 (CRM1, also known as exportin 1, XPO1). CRM1-mediated events have been implicated in breast cancer and involved in chemoimmunotherapy. microRNA-200b (miR-200b) is a cell-autonomous suppressor of EMT (epithelial-mesenchymal transition) and involved in tumor metastasis. In our present work, we discovered that miR-200b overexpression resulted in significant BRCA1 nuclear retention accompanied by downregulated expression of CRM1 and STAT1 (signal transducer and activator of transcription 1). Bioinformatics analysis indicated that miR-200b directly targets STAT1, which was confirmed by luciferase assay. We demonstrated that STAT1 is a transcription factor (TF) of CRM1, by both Transfac analysis and chromatin immunoprecipitation (ChIP)-qPCR assay. In patient tissue samples, we found that miR-200b expression was relatively lower in TNBC compared to non-TNBCs. Furthermore, we demonstrated that miR-200b-mediated BRCA1 nuclear retention is associated with significant PD-L1 downregulation, and sensitizes the TNBC cells to chemotherapeutic agents. In addition, high level PD-L1 expression is associated with not only chemoimmunoresistance but also tumor metastasis. These data provide strong evidence that miR-200b-mediated regulation of BRCA1 nucleus retention is through transcriptional regulation of CRM1 by STAT1, and miR-200b regulates PD-L1 expression in TNBC. In conclusion, this novel dual role of miR-200b may serve as a strategy in metastatic TNBC therapy by repressing STAT1-mediated CRM1 transcription regulation, and reversing the chemoimmunoresistance via PD-L1 inhibition. Citation Format: Xiaohui Tan, Shuchang Ren, Woojin Lee, Xiaoling Wu, Katayoon Rezaei, Yan-gao Man, Patricia Latham, Robert S. Siegel1, Rachel F. Brem, Zhongwu Li, Xiaofeng Chang, Sidney W. Fu. Dual functions of miR-200b in triple-negative breast cancer metastasis and chemoimmuno-resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 498.

Purpose: To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL). Methods and Materials: A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count <500 cells/mu L within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method. Results: Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P<.01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/mu L vs 900 cells/mu L, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRTand 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRTand SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different. Conclusions: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL. (C) 2018 Elsevier Inc. All rights reserved.

This chapter is especially dedicated to the optical properties of bismuth oxyhalides. The absorption and reflectance spectra to study the spectral absorption and the band-gap energies of the material, photoluminescence spectra to study the recombination of photoinduced charge-carriers are presented.

Better understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.

This chapter presents different preparation methods for bismuth oxyhalides and their relative merits, characteristics, and applicability. The method of preparation of different variants of bismuth oxyhalides includes various hydrolysis methods, preparation by heat treatment, vapor-phase synthesis, hydrothermal preparation, solvothermal preparation, and special halide source-induced preparation.

External beam radiation therapy (EBRT) treatment physician order errors are the ones associated with the very top level treatment decision parameters, especially about total prescription dose, fraction dose, fractions, modality, patient setup options, and considerations of previous treatments if applicable. Errors in physician orders are difficult to detect even to human experts without going through many data and documentations, and are also very difficult to detect digitally using simple rule based or data-value-comparison based checks. The purpose of this work is to investigate a novel machine-learning approach, based on Bayesian network models, to detect EBRT physician order errors. The goal is to catch those errors earlier so to avoid the costly re-simulation and re-planning. EBRT physician orders from 2007 to 2015 were obtained from the treatment management system (Mosaiq) at author’s institution. A total of 5374 individual orders for 14 disease sites – brain, head and neck, breast, lungs, chest wall, spine, abdomen, pelvic, pelvis, prostate, thorax, TBI, extremely, lymph nodal – were acquired (3772 single-prescription, 400 concurrent boost and 401 sequential boost cases). Each order includes disease attributes, prescription parameters, and patient setup instructions. Seven disease attributes were considered as conditions - site, tumor stage, nodal stage, metastatic stage, intent, laterality, and previous treatment. Errors were detected on the four prescription parameters - total dose, fractions, technique, and modality. Three Bayesian network models were developed corresponding to three different types of cases. Each model was designed in three layers –disease attributes, order parameters and an anomaly flag. A Bayesian learning method with Dirichlet prior was employed to train the models. The conditional joint probability of the anomaly flag and the prescription parameters were employed to detect errors in the prescription parameters with respect to the disease attributes. Ten percent of physician orders were randomly chosen and errors (wrong values in prescription parameters) were added manually for testing the performance of the method. The means values of true-positive and false-positive rates of error detection were 93.17% and 9.69%, respectively, for single-prescription cases of 14 disease sites, 91.77%, and 8.85%, respectively, for concurrent boost cases of 3 sites, and 91.63%, and 8.61%, respectively, for sequential boost cases of 5 sites. Errors on the single prescription parameters and on the prescription parameter combinations of given multiple disease attributes could be detected by the trained Bayesian network models with high positive rate. The approach supports further development of BN model incorporation into independent error detection tools for assisting manual double-checks on physician orders. The success of the method here also gives promise to further scaling to include patient setup parameters and other sites.

Iron oxide nanoparticles confined in smaller pores possess a higher surface hydroxyl density and enhanced reactivity for As(v) adsorption.

This chapter presents some important applications of bismuth oxyhalides, particularly the material’s application as a photocatalyst in the process of water purification and water splitting. Other applications covered in this chapter are the application of bismuth oxyhalides in gas sensing, in secondary batteries, and in solar cells.

This chapter is the general introduction to bismuth oxyhalides as a functional material, with the particular emphasis for their application as a photocatalyst in many photochemical processes. This introductory chapter touches upon the importance of bismuth oxyhalides, their unique characteristics, and different variants of these materials for various applications.