Interpretable (not just posthoc-explainable) medical claims modeling for discharge placement to reduce preventable all-cause readmissions or death.

We developed an inherently interpretable multilevel Bayesian framework for representing variation in regression coefficients that mimics the piecewise linearity of ReLU-activated deep neural networks. We used the framework to formulate a survival model for using medical claims to predict hospital readmission and death that focuses on discharge placement, adjusting for confounding in estimating causal local average treatment effects. We trained the model on a 5% sample of Medicare beneficiaries from 2008 and 2011, based on their 2009-2011 inpatient episodes (approximately 1.2 million), and then tested the model on 2012 episodes (approximately 400 thousand). The model scored an out-of-sample AUROC of approximately 0.75 on predicting all-cause readmissions-defined using official Centers for Medicare and Medicaid Services (CMS) methodology-or death within 30-days of discharge, being competitive against XGBoost and a Bayesian deep neural network, demonstrating that one need-not sacrifice interpretability for accuracy. Crucially, as a regression model, it provides what blackboxes cannot-its exact gold-standard global interpretation, explicitly defining how the model performs its internal "reasoning" for mapping the input data features to predictions. In doing so, we identify relative risk factors and quantify the effect of discharge placement. We also show that the posthoc explainer SHAP provides explanations that are inconsistent with the ground truth model reasoning that our model readily admits.

An Edge Transfer Learning Approach for Calibrating Soil Electrical Conductivity Sensors.

Smart agriculture utilizes Internet of Things (IoT) technologies to enable low-cost electrical conductivity (EC) sensors to support farming intelligence. Due to aging and changes in weather and soil conditions, EC sensors are prone to long-term drift over years of operation. Therefore, regular recalibration is necessary to ensure data accuracy. In most existing solutions, an EC sensor is calibrated by using the standard sensor to build the calibration table. This paper proposes SensorTalk3, an ensemble approach of machine learning models including XGBOOST and Random Forest, which can be executed at an edge device (e.g., Raspberry Pi) without GPU acceleration. Our study indicates that the soil information (both temperature and moisture sensor data) plays an important role in SensorTalk3, which significantly outperforms the existing calibration approaches. The MAPE of SensorTalk3 can be as low as 1.738%, compared to the 7.792% error of the original sensor. Our study indicates that when the errors of uncalibrated moisture and temperature sensors are not larger than 8.3%, SensorTalk3 can accurately calibrate EC. SensorTalk3 can perform model training during data collection at the edge node. When all training data are collected, AI training is also finished at the edge node. Such an AI training approach has not been found in existing edge AI approaches. We also proposed the dual-sensor detection solution to determine when to conduct recalibration. The overhead of this solution is less than twice the optimal detection scenario (which cannot be achieved practically). If the two non-standard sensors are homogeneous and stable, then the optimal detection scenario can be approached. Conventional methods require training calibration AI models in the cloud. However, SensorTalk3 introduces a significant advancement by enabling on-site transfer learning in the edge node. Given the abundance of farming sensors deployed in the fields, performing local transfer learning using low-cost edge nodes proves to be a more cost-effective solution for farmers.

AMBtalk: A Cardiovascular IoT Device for Ambulance Applications.

Acute Coronary Syndrome (ACS) and other heart emergency events require immediate chest pain identification in the ambulance. Specifically, early identification and triage is required so that patients with chest pain can be quickly sent to a hospital with appropriate care facilities for treatment. In the traditional approach, ambulance personnel often use symptom checklists to examine the patient and make a quick decision for the target hospital. However, not every hospital has specialist facilities to handle such emergency cases. If the result of the subsequent cardiac enzyme test performed at the target hospital strongly suggests the occurrence of myocardial infarction, the patient may need to be sent to another hospital with specialist facilities, such as Percutaneous Coronary Intervention. The standard procedure is time consuming, which may result in delayed treatment and reduce patent survival rate. To resolve this issue, we propose AMBtalk (Ambulance Talk) for accurate, early ACS identification in an ambulance. AMBtalk provides real-time connection to hospital resources, which reduces the elapsed time for treatment, and therefore, improves the patient survival rate. The key to success for AMBtalk is the development of the AllCheck® Internet of Things (IoT) device, which can accurately and quickly provide cardiovascular parameter values for early ACS identification. The interactions between the AllCheck® IoT device, the emergency medical service center, the ambulance personnel and the hospital are achieved through the AMBtalk IoT server in the cloud network. AllCheck® outperforms the existing cardiovascular IoT device solutions for ambulance applications. The testing results of the AllCheck® device show 99% correlation with the results of the hospital reports. Due to its excellent performance in quick ACS identification, the AllCheck® device was awarded the 17th Taiwan Innovators Award in 2020.

The crossroads of breast cancer progression: insights into the modulation of major signaling pathways.

Cancer is the disease with highest public health impact in developed countries. Particularly, breast cancer has the highest incidence in women worldwide and the fifth highest mortality in the globe, imposing a significant social and economic burden to society. The disease has a complex heterogeneous etiology, being associated with several risk factors that range from lifestyle to age and family history. Breast cancer is usually classified according to the site of tumor occurrence and gene expression profiling. Although mutations in a few key genes, such as BRCA1 and BRCA2, are associated with high breast cancer risk, the large majority of breast cancer cases are related to mutated genes of low penetrance, which are frequently altered in the whole population. Therefore, understanding the molecular basis of breast cancer, including the several deregulated genes and related pathways linked to this pathology, is essential to ensure advances in early tumor detection and prevention. In this review, we outline key cellular pathways whose deregulation has been associated with breast cancer, leading to alterations in cell proliferation, apoptosis, and the delicate hormonal balance of breast tissue cells. Therefore, here we describe some potential breast cancer-related nodes and signaling concepts linked to the disease, which can be positively translated into novel therapeutic approaches and predictive biomarkers.

Influencing Selectivity to Cancer Cells with Mixed Nanoparticles Prepared from Albumin-Polymer Conjugates and Block Copolymers.

Albumin-based nanoparticles are widely used to delivery anticancer drug because they promote the accumulation of drugs in tumor sites. Nanoparticles with surface immobilized albumin are widely described in literature, although mixed nanoparticles with systematically modified ratios between albumin and PEG-based material are less common. In this work, hybrid nanoparticles were prepared by coassembly of a PEG-based amphiphilic block copolymer together with a polymer-protein conjugate. Poly(oligo(ethylene glycol) methyl ether acrylate)-poly(ε-caprolactone) (POEGMEA-PCL) was prepared by a combination of ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, while the polymer-protein conjugate was obtained by reacting poly(ε-caprolactone) with bovine serum albumin (BSA-PCL). Co-assembly of both amphiphiles at different ratios, with and without curcumin as a drug, led to hybrid nanoparticles with various amount of albumin on the particle surface. The resulting hybrid nanoparticles were similar in size (100-120 nm), but increasing the amount of albumin on the surface led to a more-negative ζ potential. The cytotoxicity of the curcumin-loaded nanoparticles was examined on several cell lines. The curcumin-loaded nanoparticles with high amount of albumin led to high cytotoxicity against breast cancer cell lines (MDA-MB-231 and MCF-7), which coincided with high cellular uptake. However, the cytotoxicity of the curcumin-loaded nanoparticles against CHO cells and RAW264.7 cells was reduced, suggesting that albumin can facilitate selectivity toward cancer cells.

A p57 conditional mutant allele that allows tracking of p57-expressing cells.

p57Kip2 (p57) is a maternally expressed imprinted gene regulating growth arrest which belongs to the CIP/KIP family of cyclin-dependent kinase inhibitors. While initially identified as a cell cycle arrest protein through inhibition of cyclin and cyclin-dependent kinase complexes, p57 activity has also been linked to differentiation, apoptosis, and senescence. In addition, p57 has recently been shown to be involved in tumorigenesis and cell fate decisions in stem cells. Yet, p57 function in adult tissues remains poorly characterized due to the perinatal lethality of p57 knock-out mice. To analyze p57 tissue-specific activity, we generated a conditional mouse line (p57FL-ILZ/+ ) by flanking the coding exons 2-3 by LoxP sites. To track p57-expressing or mutant cells, the p57FL-ILZ allele also contains an IRES-linked ß-galactosidase reporter inserted in the 3' UTR of the gene. Here, we show that the ß-galactosidase reporter expression pattern recapitulates p57 tissue specificity during development and in postnatal mice. Furthermore, we crossed the p57FL-ILZ/+ mice with PGK-Cre mice to generate p57cKO-ILZ/+ animals with ubiquitous loss of p57. p57cKO-ILZ/+ mice display developmental phenotypes analogous to previously described p57 knock-outs. Thus, p57FL-ILZ/+ is a new genetic tool allowing expression and functional conditional analyses of p57.

Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis.

Skeletal muscle growth and regeneration require a population of muscle stem cells, the satellite cells, located in close contact to the myofiber. These cells are specified during fetal and early postnatal development in mice from a Pax3/7 population of embryonic progenitor cells. As little is known about the genetic control of their formation and maintenance, we performed a genome-wide chronological expression profile identifying the dynamic transcriptomic changes involved in establishment of muscle stem cells through life, and acquisition of muscle stem cell properties. We have identified multiple genes and pathways associated with satellite cell formation, including set of genes specifically induced (EphA1, EphA2, EfnA1, EphB1, Zbtb4, Zbtb20) or inhibited (EphA3, EphA4, EphA7, EfnA2, EfnA3, EfnA4, EfnA5, EphB2, EphB3, EphB4, EfnBs, Zfp354c, Zcchc5, Hmga2) in adult stem cells. Ephrin receptors and ephrins ligands have been implicated in cell migration and guidance in many tissues including skeletal muscle. Here we show that Ephrin receptors and ephrins ligands are also involved in regulating the adult myogenic program. Strikingly, impairment of EPHB1 function in satellite cells leads to increased differentiation at the expense of self-renewal in isolated myofiber cultures. In addition, we identified new transcription factors, including several zinc finger proteins. ZFP354C and ZCCHC5 decreased self-renewal capacity when overexpressed, whereas ZBTB4 increased it, and ZBTB20 induced myogenic progression. The architectural and transcriptional regulator HMGA2 was involved in satellite cell activation. Together, our study shows that transcriptome profiling coupled with myofiber culture analysis, provides an efficient system to identify and validate candidate genes implicated in establishment/maintenance of muscle stem cells. Furthermore, tour de force transcriptomic profiling provides a wealth of data to inform for future stem cell-based muscle therapies.

Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium.

The transcriptional repressor Tbx3 is involved in lineage specification in several tissues during embryonic development. Germ-line mutations in the Tbx3 gene give rise to Ulnar-Mammary Syndrome (comprising reduced breast development) and Tbx3 is required for mammary epithelial cell identity in the embryo. Notably Tbx3 has been implicated in breast cancer, which develops in adult mammary epithelium, but the role of Tbx3 in distinct cell types of the adult mammary gland has not yet been characterized. Using a fluorescent reporter knock-in mouse, we show that in adult virgin mice Tbx3 is highly expressed in luminal cells that express hormone receptors, and not in luminal cells of the alveolar lineage (cells primed for milk production). Flow cytometry identified Tbx3 expression already in progenitor cells of the hormone-sensing lineage and co-immunofluorescence confirmed a strict correlation between estrogen receptor (ER) and Tbx3 expression in situ. Using in vivo reconstitution assays we demonstrate that Tbx3 is functionally relevant for this lineage because knockdown of Tbx3 in primary mammary epithelial cells prevented the formation of ER+ cells, but not luminal ER- or basal cells. Interestingly, genes that are repressed by Tbx3 in other cell types, such as E-cadherin, are not repressed in hormone-sensing cells, highlighting that transcriptional targets of Tbx3 are cell type specific. In summary, we provide the first analysis of Tbx3 expression in the adult mammary gland at a single cell level and show that Tbx3 is important for the generation of hormone-sensing cells.

Influence of the disc-fovea angle on limits of RNFL variability and glaucoma discrimination.

PURPOSE: To determine factors affecting the disc-fovea angle (DFA), and to test the hypotheses that adjusting for DFA improves limits of retinal nerve fiber layer (RNFL) variability in normal subjects or enhances performance of RNFL measures for glaucoma detection. METHODS: Disc-fovea angle was measured on scanning laser ophthalmoscope fundus images from 170 eyes (110 normal and glaucoma subjects). The DFA measurements were repeated in 24 eyes. The relationship between DFA and various anatomic variables was explored. Main outcome measures were changes in 95% RNFL prediction limits or glaucoma discrimination after adjusting for DFA. We also explored the angle between temporal raphe and horizontal meridian in 19 eyes with nasal field defects limited to one hemifield. RESULTS: Average mean deviation and DFA were -0.1 (±1.2) dB and -6.6° (±3.4°) and -4.1 (±3.3) dB and -7.9° (±3.9°) in the control and glaucoma groups, respectively (P < 0.001 and = 0.029). The average difference between DFA repeat measurements was 2.0° (±1.8°). Predictors for DFA were female sex (P = 0.004), smaller disc area (P = 0.006), and glaucoma diagnosis (P = 0.019). The absolute change in sectoral RNFL thickness was 6.1 (±3.9) and 4.6 (±3.1) µm in control and glaucoma subjects, respectively. Retinal nerve fiber layer prediction limits improved in 5, 9, and 10 o'clock sectors (P < 0.02). Discrimination ability for the best-performing RNFL sector did not improve (P = 0.936). The average angle between temporal raphe and horizontal meridian was 0.8° (±0.8°). CONCLUSIONS: Disc-fovea angle measurements demonstrated fair intersession repeatability. While adjusting for DFA improved RNFL prediction limits in some sectors, it did not enhance glaucoma detection.

Antagonistic regulation of p57kip2 by Hes/Hey downstream of Notch signaling and muscle regulatory factors regulates skeletal muscle growth arrest.

A central question in development is to define how the equilibrium between cell proliferation and differentiation is temporally and spatially regulated during tissue formation. Here, we address how interactions between cyclin-dependent kinase inhibitors essential for myogenic growth arrest (p21(cip1) and p57(kip2)), the Notch pathway and myogenic regulatory factors (MRFs) orchestrate the proliferation, specification and differentiation of muscle progenitor cells. We first show that cell cycle exit and myogenic differentiation can be uncoupled. In addition, we establish that skeletal muscle progenitor cells require Notch signaling to maintain their cycling status. Using several mouse models combined with ex vivo studies, we demonstrate that Notch signaling is required to repress p21(cip1) and p57(kip2) expression in muscle progenitor cells. Finally, we identify a muscle-specific regulatory element of p57(kip2) directly activated by MRFs in myoblasts but repressed by the Notch targets Hes1/Hey1 in progenitor cells. We propose a molecular mechanism whereby information provided by Hes/Hey downstream of Notch as well as MRF activities are integrated at the level of the p57(kip2) enhancer to regulate the decision between progenitor cell maintenance and muscle differentiation.

Influence of correction of ocular magnification on spectral-domain OCT retinal nerve fiber layer measurement variability and performance.

PURPOSE: To analyze the influence of ocular magnification on the peripapillary retinal nerve fiber layer (RNFL) thickness measurement and its performance as acquired with spectral-domain optical coherence tomography (SD-OCT). METHODS: Spectral domain OCT measurements from 108 normal eyes (59 subjects) and 72 glaucoma eyes (58 patients) were exported and custom software was used to correct RNFL measurements for ocular magnification. Retinal nerve fiber layer prediction limits in normal subjects, structure-function relationships, and RNFL performance for detection of glaucoma were compared before and after correction for ocular magnification (Bennett's formula). Association of disc area with cross-sectional RNFL area was explored. RESULTS: The median (interquartile range, [IQR]) visual field mean deviation and scaling factor were 0 (-0.85 to 0.73) dB and 0.96 (0.93-1.00) in normal eyes and -4.0 (-6.0 to -2.2) dB and 0.99 (0.95-1.03) in the glaucoma group (P < 0.001 and P = 0.003, respectively; average correction 3%). Correction for ocular magnification caused a reversal of the negative relationship between the cross-sectional RNFL area and axial length (slope = -0.022 mm(2)/mm, P = 0.015 vs. = 0.22 mm(2)/mm, P = 0.007). However, such correction did not change RNFL prediction limits (except in superior and nasal quadrants), improve global or regional structure-function relationships, or enhance the ability of RNFL measurements to discriminate glaucoma from normal eyes (P > 0.05). The cross-sectional RNFL area was not correlated with optic disc area (P = 0.325). CONCLUSIONS: Correction of RNFL measurements for ocular magnification did not improve prediction limits in normal subjects or enhance the performance of SD-OCT in this group of eyes in which the axial length did not deviate significantly from average values. The cross-sectional area of the RNFL was not related to the optic disc area.

Radioembolization and the Dynamic Role of (90)Y PET/CT.

Before the advent of tomographic imaging, it was postulated that decay of (90) Y to the 0(+) excited state of (90)Zr may result in emission of a positron-electron pair. While the branching ratio for pair-production is small (~32 × 10(-6)), PET has been successfully used to image (90) Y in numerous recent patients and phantom studies. (90) Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF) and/or resolution recovery capabilities as well as on both bismuth-germanate and lutetium yttrium orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in LYSO-based PET scanners is a potential limitation associated with accurate quantification of (90) Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in (90) Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative (90) Y PET images can be transformed into 3-dimensional (3D) maps of absorbed dose based on the premise that the (90) Y activity distribution does not change after infusion. This transformation has been accomplished in several ways, although the most common is with the use of 3D dose-point-kernel convolution. From a clinical standpoint, (90) Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment-planning for successive therapies, potentially improving response. The broad utilization of (90) Y PET has the potential to provide a wealth of dose-response information, which may lead to development of improved radioembolization treatment-planning models in the future.

New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.

INTRODUCTION: Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. METHODS: We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. RESULTS: After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. CONCLUSIONS: Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis.

Intraprocedural yttrium-90 positron emission tomography/CT for treatment optimization of yttrium-90 radioembolization.

Radioembolization with yttrium-90 ((90)Y) microspheres relies on delivery of appropriate treatment activity to ensure patient safety and optimize treatment efficacy. We report a case in which (90)Y positron emission tomography (PET)/computed tomography (CT) was performed to optimize treatment planning during a same-day, three-part treatment session. This treatment consisted of (i) an initial (90)Y infusion with a dosage determined using an empiric treatment planning model, (ii) quantitative (90)Y PET/CT imaging, and (iii) a secondary infusion with treatment planning based on quantitative imaging data with the goal of delivering a specific total tumor absorbed dose.

Online training on the safe use of fluoroscopy can result in a significant decrease in patient dose.

RATIONALE AND OBJECTIVES: Concerns over medical radiation exposure have received national press in recent years, and training in the appropriate use of radiation has become an essential component of every radiology residency program. Appropriate training is particularly important in fluoroscopy because it is commonly used by inexperienced radiology residents and has the potential to impart relatively high patient radiation doses. In an effort to minimize the radiation doses received by patients, our institution has recently initiated an online training program in the safe use of fluoroscopy. This course is required and must be completed by new radiology residents before their first fluoroscopy rotation. The goal of this study was to determine if the use of an online course in the safe use of fluoroscopy could result in decreased patient dose without affecting diagnostic quality. MATERIALS AND METHODS: Four years of retrospective procedural data for residents performing gastrointestinal and genitourinary fluoroscopic procedures without specialized training were reviewed. Incoming residents took an American Medical Association-accredited online training program in the safe use of fluoroscopy the week before their first fluoroscopy rotation. Patient dose and diagnostic quality data, inferred from the frequency of attending physician intervention necessary to complete the procedure, were collected for all exams performed by the new group of residents after completion of the training course. This was then compared to data from prior classes and stratified by procedure type. RESULTS: Statistically significant reductions in both average fluoroscopy time (FT) or dose-area-product (DAP) were found for many of the fluoroscopic procedures performed by residents who participated in the online fluoroscopy training program. Specifically, statistically significant reductions in FT for barium enema, cystogram, defecogram, and esophagram procedures (P < .001) were found. Esophagram and upper gastrointestinal studies were completed with a significantly lower DAP (P < .001). The average reduction in DAP across all procedures performed by first-year residents was 38%, whereas the average reduction in FT was 25%. Based on a review of data from all procedures performed, there was no statistically significant loss in diagnostic quality. CONCLUSION: An online training program can be effectively used to provide radiation safety instruction immediately before the start of a resident's fluoroscopy rotation, decreasing patient dose without affecting diagnostic quality.

Role of positron emission tomography/computed tomography in breast cancer.

Although positron emission tomography (PET) imaging may not be used in the diagnosis of breast cancer, the use of PET/computed tomography is imperative in all aspects of breast cancer staging, treatment, and follow-up. PET will continue to be relevant in personalized medicine because accurate tumor status will be even more critical during and after the transition from a generic metabolic agent to receptor imaging. Positron emission mammography is an imaging proposition that may have benefits in lower doses, but its use is limited without new radiopharmaceuticals.

Positron emission tomography/computed tomography in melanoma.

Fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) has been invaluable in the assessment of melanoma throughout the course of the disease. As with any modality, the studies are incomplete and more information will be gleaned as our experience progresses. Additionally, it is hoped that a newer PET agent in the pipeline will give us even greater success in the identification and subsequent treatment of melanoma. This article aims to examine the utilization of PET/CT in the staging, prognostication, and follow-up of melanoma while providing the physicians who order and interpret these studies practical guidelines and interpretive pitfalls.

Itm2a is a Pax3 target gene, expressed at sites of skeletal muscle formation in vivo.

The paired-box homeodomain transcription factor Pax3 is a key regulator of the nervous system, neural crest and skeletal muscle development. Despite the important role of this transcription factor, very few direct target genes have been characterized. We show that Itm2a, which encodes a type 2 transmembrane protein, is a direct Pax3 target in vivo, by combining genetic approaches and in vivo chromatin immunoprecipitation assays. We have generated a conditional mutant allele for Itm2a, which is an imprinted gene, by flanking exons 2-4 with loxP sites and inserting an IRESnLacZ reporter in the 3' UTR of the gene. The LacZ reporter reproduces the expression profile of Itm2a, and allowed us to further characterize its expression at sites of myogenesis, in the dermomyotome and myotome of somites, and in limb buds, in the mouse embryo. We further show that Itm2a is not only expressed in adult muscle fibres but also in the satellite cells responsible for regeneration. Itm2a mutant mice are viable and fertile with no overt phenotype during skeletal muscle formation or regeneration. Potential compensatory mechanisms are discussed.

Treatment modification of yttrium-90 radioembolization based on quantitative positron emission tomography/CT imaging.

Treatment activity for yttrium-90 ((90)Y) radioembolization when calculated by using the manufacturer-recommended technique is only partially patient-specific and may result in a subtumoricidal dose in some patients. The authors describe the use of quantitative (90)Y positron emission tomography/computed tomography as a tool to provide patient-specific optimization of treatment activity and evaluate this new method in a patient who previously received traditional (90)Y radioembolization. The modified treatment resulted in a 40-Gy increase in absorbed dose to tumor and complete resolution of disease in the treated area within 3 months.

Chlorogenic acid attenuates adhesion molecules upregulation in IL-1beta-treated endothelial cells.

BACKGROUND: Expression of cell adhesion molecules (CAM) on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. Chlorogenic acid is a phenolic compound present in coffee, apples, pears, berries, almonds, artichokes, and aubergines. Previous studies have indicated that CA possesses antioxidant activity in vitro. AIM: We investigated the effects of chlorogenic acid and probucol on monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation and ROS production in IL-1beta-induced human umbilical vein endothelial cells (HUVECs). RESULTS: According to the results of the MTT assay, we chose 25 and 50 mumol/L to perform the experiments. Chlorogenic acid dose-dependently suppressed IL-1beta-induced mRNA expression of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1 and endothelial cell selectin. Chlorogenic acid also suppressed the IL-1beta-induced production of ROS. We also observed that chlorogenic acid attenuated or blocked IL-1beta-induced nuclear translocation of nuclear factor-kappaB subunits p50 and p65, which in turn attenuated CAM expression at the transcription level. Furthermore, chlorogenic acid significantly reduced the adhesion of human monocyte cells (U937) to IL-1beta-treated HUVECs in a dose-response manner. These results are similar to that of probucol. CONCLUSIONS: We conclude that chlorogenic acid exhibit anti-inflammatory effects in HUVECs by inhibition of U937 monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation, and ROS production. The anti-inflammatory activity of chlorogenic acid in HUVECs suggests that chlorogenic acid could be useful in the prevention of atherosclerosis.