bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel MRI segmentation method using CNN‐based correction network for MRI‐guided adaptive radiotherapy
Authors: Fu Yabo , Mazur Thomas R. , Wu Xue , Liu Shi , Chang Xiao , Lu Yonggang , Li H. Harold , Kim Hyun , Roach Michael C. , Henke Lauren , Yang Deshan 
Published: September 2018

PurposeThe purpose of this study was to expedite the contouring process for MRI‐guided adaptive radiotherapy (MR‐IGART), a convolutional neural network (CNN) deep‐learning (DL) model is proposed to accurately segment the liver, kidneys, stomach, bowel and duodenum in 3D MR images.MethodsImages and structure contours for 120 patients were collected retrospectively. Treatment sites included pancreas, liver, stomach, adrenal gland, and prostate. The proposed DL model contains a voxel‐wise label prediction CNN and a correction network which consists of two sub‐networks. The prediction CNN and sub‐networks in the correction network each includes a dense block which consists of twelve densely connected convolutional layers. The correction network was designed to improve the voxel‐wise labeling accuracy of a CNN by learning and enforcing implicit anatomical constraints in the segmentation process. Its sub‐networks learn to fix the erroneous classification of its previous network by taking as input both the original images and the softmax probability maps generated from its previous sub‐network. The parameters of each sub‐network were trained independently using piecewise training. The model was trained on 100 datasets, validated on 10 datasets and tested on the remaining 10 datasets. Dice coefficient, Hausdorff distance (HD) were calculated to evaluate the segmentation accuracy.ResultsThe proposed DL model was able to segment the organs with good accuracy. The correction network outperformed the conditional random field (CRF), a most comparable method that is usually applied as a post‐processing step. For the 10 testing patients, the average Dice coefficients were 95.3 ± 0.73, 93.1 ± 2.22, 85.0 ± 3.75, 86.6 ± 2.69, and 65.5 ± 8.90 for liver, kidneys, stomach, bowel, and duodenum, respectively. The mean Hausdorff Distance (HD) were 5.41 ± 2.34, 6.23 ± 4.59, 6.88 ± 4.89, 5.90 ± 4.05, and 7.99 ± 6.84 mm, respectively. Manual contouring, as to correct the automatic segmentation results, was four times as fast as manual contouring from scratch.ConclusionThe proposed method can automatically segment the liver, kidneys, stomach, bowel, and duodenum in 3D MR images with good accuracy. It is useful to expedite the manual contouring for MR‐IGART.
Orientation dependence and decay characteristics of T2* relaxation in the human meniscus studied with 7 Tesla MR microscopy and compared to histology
Authors: Hager Benedikt , Walzer Sonja M. , Deligianni Xeni , Bieri Oliver , Berg Andreas , Schreiner Markus M. , Zalaudek Martin , Windhager Reinhard , Trattnig Siegfried , Juras Vladimir 
Published: September 2018

PurposeTo evaluate: (1) the feasibility of MR microscopy T2* mapping by performing a zonal analysis of spatially matched T2* maps and histological images using microscopic in‐plane pixel resolution; (2) the orientational dependence of T2* relaxation of the meniscus; and (3) the T2* decay characteristics of the meniscus by statistically evaluating the quality of mono‐ and biexponential model.MethodsUltrahigh resolution T2* mapping was performed with ultrashort echo time using a 7 Tesla MR microscopy system. Measurement of one meniscus was performed at three orientations to the main magnetic field (0, 55, and 90°). Histological assessment was performed with picrosirius red staining and polarized light microscopy. Quality of mono‐ and biexponential model fitting was tested using Akaike Information Criteria and F‐test.Results(1) The outer laminar layer, connective tissue fibers from the joint capsule, and the highly organized tendon‐like structures were identified using ultra‐highly resolved MRI. (2) Highly organized structures of the meniscus showed considerable changes in T2* values with orientation. (3) No significant biexponential decay was found on a voxel‐by‐voxel–based evaluation. On a region‐of‐interest–averaged basis, significant biexponential decay was found for the tendon‐like region in a fiber‐to‐field angle of 0°.ConclusionThe MR microscopy approach used in this study allows the identification of meniscus substructures and to quantify T2* with a voxel resolution approximately 100 times higher than previously reported. T2* decay showed a strong fiber‐to‐field angle dependence reflecting the anisotropic properties of the meniscal collagen fibers. No clear biexponential decay behavior was found for the meniscus substructures.
Sleep duration, timing, variability and measures of adiposity among 8‐ to 12‐year‐old children with obesity
Authors: Zhou M. , Lalani C. , Banda J. A. , Robinson T. N. 
Published: October 2018

SummaryObjectivesSleep disruption in laboratory studies increases adiposity and decreases glucose tolerance. However, few epidemiological studies have used objective measures of sleep. This study aims to assess associations between sleep duration, timing and regularity with measures of adiposity.MethodsThis is a cross‐sectional study of 188 children with obesity (age: 10.50 ± 1.39 years; body mass index: 29.24 ± 5.04 kg m−2). Nightly sleep duration, bedtime and wake time were measured by multiple‐day actigraphy and parent reports. Per cent overweight (per cent over median body mass index for age and sex) was chosen as the primary measure of obesity status. Objective measures of height, weight, waist circumference, blood pressure, fasting blood lipids, glucose, insulin, glycated haemoglobin and C‐reactive protein were obtained. Television screen time and total caloric intake were assessed via parent questionnaire.ResultsEach hour later in weekday bedtime was associated with an additional 6.17 per cent overweight (95% confidence interval [CI]: 1.42–10.92). Each hour greater in day‐to‐day variability in weekday bedtime and weekday wake time was associated with an additional 10.20 (95% CI: 0.50–19.91) and 10.02 (95% CI: 1.55–18.50) per cent overweight, respectively. Associations were similar after controlling for other obesity‐related behaviours (television screen time, total caloric intake and physical activity.)ConclusionsAmong children with obesity, later bedtime and greater variability in bedtime and wake time are associated with greater adiposity, independent of other obesity‐related behaviours. Early bedtime and wake time and consistent day‐to‐day sleep timing may be strategies to reduce adiposity in high‐risk children.
Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis
Authors: Yoshida Ken , Nakashima Ayumu , Doi Shigehiro , Ueno Toshinori , Okubo Tomoe , Kawano Ki-ichiro , Kanawa Masami , Kato Yukio , Higashi Yukihito , Masaki Takao 
Published: September 2018

Abstract
Serum used in culture medium brings risks of immune reactions or infections and thus may hinder using ex vivo expanded mesenchymal stem cells (MSCs) for medical treatment. Here, we cultured MSCs in a serum-free medium (SF-MSCs) and in a medium containing 10% fetal bovine serum (10%MSCs) and investigated their effects on inflammation and fibrosis. MSC-conditioned medium suppressed transforming growth factor-β1–induced phosphorylation of Smad2 in HK-2 cells, with no significant difference between the two MSCs. This finding suggests that the direct antifibrotic effect of SF-MSCs is similar to that of 10%MSCs. However, immunohistochemistry revealed that renal fibrosis induced by unilateral ureteral obstruction in rats was more significantly ameliorated by the administration of SF-MSCs than by that of 10%MSCs. Coculture of MSCs and monocytic THP-1 cell-derived macrophages using a Transwell system showed that SF-MSCs significantly induced polarization from the proinflammatory M1 to the immunosuppressive M2 phenotype macrophages, suggesting that SF-MSCs strongly suppress the persistence of inflammation. Furthermore, the gene expression of tumor necrosis factor-α–induced protein 6 (TSG-6), which inhibits the recruitment of inflammatory cells, was higher in SF-MSCs than in 10%MSCs, and TSG-6 knockdown in SF-MSCs attenuated the anti-inflammatory responses in unilateral ureteral obstruction rats. These findings imply that SF culture conditions can enhance the immunosuppressive and antifibrotic abilities of MSCs and the administration of ex vivo expanded SF-MSCs has the potential to be a useful therapy for preventing the progression of renal fibrosis.
Limited Endothelial Plasticity of Mesenchymal Stem Cells Revealed by Quantitative Phenotypic Comparisons to Representative Endothelial Cell Controls
Authors: Antonyshyn Jeremy A. , McFadden Meghan J. , Gramolini Anthony O. , Hofer Stefan O.P. , Santerre J. Paul 
Published: September 2018

Abstract
Considerable effort has been directed toward deriving endothelial cells (ECs) from adipose-derived mesenchymal stem cells (ASCs) since 2004, when it was first suggested that ECs and adipocytes share a common progenitor. While the capacity of ASCs to express endothelial markers has been repeatedly demonstrated, none constitute conclusive evidence of an endothelial phenotype as all reported markers have been detected in other, non-endothelial cell types. In this study, quantitative phenotypic comparisons to representative EC controls were used to determine the extent of endothelial differentiation being achieved with ASCs. ASCs were harvested from human subcutaneous abdominal white adipose tissue, and their endothelial differentiation was induced using well-established biochemical stimuli. Reverse transcription quantitative real-time polymerase chain reaction and parallel reaction monitoring mass spectrometry were used to quantify their expression of endothelial genes and corresponding proteins, respectively. Flow cytometry was used to quantitatively assess their uptake of acetylated low-density lipoprotein (AcLDL). Human umbilical vein, coronary artery, and dermal microvascular ECs were used as positive controls to reflect the phenotypic heterogeneity between ECs derived from different vascular beds. Biochemically conditioned ASCs were found to upregulate their expression of endothelial genes and proteins, as well as AcLDL uptake, but their abundance remained orders of magnitude lower than that observed in the EC controls despite their global proteomic heterogeneity. The findings of this investigation demonstrate the strikingly limited extent of endothelial differentiation being achieved with ASCs using well-established biochemical stimuli, and underscore the importance of quantitative phenotypic comparisons to representative primary cell controls in studies of differentiation. Stem Cells Translational Medicine 2019;8:35–45
Going Vertical
Authors: Toyne J. Marla , Anzellini Armando , Epstein Mičulka Lori , Mejías Pitti Ismael , Puig Castell Jordi , Guinot Castelló Salvador 
Published: October 2018

ABSTRACTMost archaeological practice involves horizontal excavations of ancient occupations and cemeteries, but the Chachapoya of Peru's eastern montane built tombs along narrow cliff ledges, which require innovative methods of investigation. Many of these sites are becoming exposed and threatened due to increased deforestation. The La Petaca mortuary complex includes 125 constructed platforms, modified ledges, mausoleums, and caves containing human remains across one section of an exposed rock face approximately 200 m across by approximately 80 m high. While the site has been looted and damaged due to various taphonomic processes (including ecological, geological, and cultural), we argue that there are recoverable details, especially in relation to how the ancient Chachapoya people created and accessed these vertical spaces. Through collaboration with technical professionals, we identified and documented many tombs using vertical progression techniques. This valuable partnership between spelunkers and archaeologists allowed us to develop techniques for “vertical archaeology,” including safe access in order to be able to document, sample, and make detailed observations of building methods and burial contents.
Release and speciation of carbon from Zircaloy-4 in anaerobic and highly alkaline conditions: Comparison of simple immersion and potentiostatic corrosion tests
Authors: Caes Sebastien , Druyts Frank , Thomas Peter 
Published: October 2018

ABSTRACTThe gas release and speciation of carbon species from irradiated and unirradiated Zircaloy-4 samples, representative for the fuel cladding as used in Belgian nuclear power plants, were studied in a saturated Ca(OH)2 solution in anaerobic conditions. This environment is relevant for the Belgian Supercontainer design, as perceived for the geological disposal of high-level nuclear waste. To achieve this, we performed simple immersion and potentiostatic corrosion tests. Potentiodynamic polarization curves, recorded prior to the potentiostatic tests, revealed that irradiation seems to induce changes on the Zircaloy-4 corrosion behavior, such as a shift of the corrosion potential. Potentiostatic corrosion tests on unirradiated Zircaloy-4 provided a corrosion rate of ~54 nm/yr over a 7 day-experiment, whilst a corrosion rate of only ~4 nm/yr was calculated for the irradiated sample. Gas chromatography revealed that during simple immersion tests, which lasted 195 days, hydrogen, methane, ethane, and CO2 were produced, with methane being the major compound. Assuming that all carbon released from the metal was transformed into gaseous compounds, this yields to a corrosion rate ranging from 57 to 84 nm/yr for the irradiated sample. However, caution has to be taken on these corrosion rate and more tests should be performed to confirm these results.
Chronic lymphocytic leukemia treatment algorithm 2018
Authors: Parikh Sameer A. 
Published: October 2018

Abstract
The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as ibrutinib, idelalisib, and venetoclax), and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in CLL, even among patients with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. Each of these treatments is associated with a unique toxicity profile; in the absence of randomized data, the choice of one type of treatment over another depends on the co-morbidities of the patient. Chemoimmunotherapy still plays an important role in the management of previously untreated CLL patients, particularly among young fit patients who have standard risk FISH profile and mutated IGHV genes. Richter’s transformation of CLL remains a difficult complication to treat, although therapy with programmed death 1 inhibitors such as pembrolizumab and nivolumab has shown impressive responses in a subset of patients. Our ability to risk stratify CLL patients continues to evolve; the CLL-International Prognostic Index (CLL-IPI) is the best validated tool in predicting time to first therapy among previously untreated patients. This review summarizes the current approach to risk stratification and management of CLL patients.
Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1
Authors: Singhal Ashutosh , Szente Lajos , Hildreth James E. K. , Song Byeongwoon 
Published: October 2018

AbstractNiemann–Pick type C (NPC) disease is a fatal hereditary neurodegenerative disorder characterized by a massive accumulation of cholesterol in lysosomes and late endosomes due to a defect in intracellular cholesterol trafficking. Dysfunction in intracellular cholesterol trafficking is responsible for about 50 rare inherited lysosomal storage disorders including NPC. The lysosomal proteins NPC1 and NPC2 play a crucial role in trafficking of cholesterol from late endosomes and lysosomes to other cellular compartments. However, the detailed mechanisms of cholesterol trafficking at the late endosomes/lysosomes (LE/LY) are poorly understood. Studies showed that 2-hydroxypropyl-β-cyclodextrin (HPβCD) alleviates the cholesterol accumulation defect in animal model and has been approved for a phase 2b/3 clinical trial for NPC. HPβCD is known to bind cholesterol; however, the mechanisms how HPβCD mediates the exit of cholesterol from the LE/LY compartments are still unknown. Further, another cyclodextrin (CD) derivative, 2-hydroxypropyl-γ-cyclodextrin (HPγCD), was shown to reduce intracellular cholesterol accumulation in NPC patient cells and NPC mice model. Herein, we identified a number of candidate proteins differentially expressed in NPC patient-derived cells compared to cells derived from a healthy donor using a proteomic approach. Interestingly, both HPβCD and HPγCD treatments modulated the expression of most of these NPC-specific proteins. Data showed that treatment with both CDs induces the expression of the lysosome-associated membrane protein 1 (LAMP-1) in NPC patient-derived cells. Remarkably, LAMP-1 overexpression in HeLa cells rescued U18666A-induced cholesterol accumulation suggesting a role of LAMP-1 in cholesterol trafficking. We propose that HPβCD and HPγCD facilitate cholesterol export from the LE/LY compartments via the LAMP-1 protein, which may play a crucial role in cholesterol trafficking at the LE/LY compartments when there is no functional NPC1 protein. Together, this study uncovers new cellular mechanisms for cholesterol trafficking, which will contribute to development of novel therapeutic approaches for lysosomal storage diseases.
LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212
Authors: Yu Fujun , Geng Wujun , Dong Peihong , Huang Zhiming , Zheng Jianjian 
Published: October 2018

AbstractActivation of hepatic stellate cells (HSCs), a pivotal event in liver fibrosis, is considered as an epithelial–mesenchymal transition (EMT) process. Deregulation of long noncoding RNAs (lncRNAs) has been reported to be involved in a series of human diseases. LncRNA-maternally expressed gene 3 (MEG3) functions as a tumor suppressor in cancers and has been shown to play a vital role in EMT process. However, the biological role of MEG3 in liver fibrosis is largely unknown. In this study, MEG3 was reduced in vivo and in vitro during liver fibrosis. Restoring of MEG3 expression led to the suppression of liver fibrosis, with a reduction in α-SMA and type I collagen. Notably, MEG3 overexpression inhibited HSC activation through EMT, associated with an increase in epithelial markers and a reduction in mesenchymal markers. Further studies showed that Hedgehog (Hh) pathway-mediated EMT process was involved in the effects of MEG3 on HSC activation. Smoothened (SMO) is a member of Hh pathway. Using bioinformatic analysis, an interaction between MEG3 and SMO protein was predicted. This interaction was confirmed by the results of RNA immunoprecipitation and deletion-mapping analysis. Furthermore, MEG3 was confirmed as a target of microRNA-212 (miR-212). miR-212 was partly responsible for the effects of MEG3 on EMT process. Interestingly, MEG3 was also reduced in chronic hepatitis B (CHB) patients with liver fibrosis when compared with healthy controls. MEG3 negatively correlated with fibrosis stage in CHB patients. In conclusion, we demonstrate that MEG3 inhibits Hh-mediated EMT process in liver fibrosis via SMO protein and miR-212.
Exceptional catalytic effects of black phosphorus quantum dots in shuttling-free lithium sulfur batteries
Authors: Xu Zheng-Long , Lin Shenghuang , Onofrio Nicolas , Zhou Limin , Shi Fangyi , Lu Wei , Kang Kisuk , Zhang Qiang , Lau Shu Ping 
Published: October 2018

AbstractLithium sulfur batteries with high energy densities are promising next-generation energy storage systems. However, shuttling and sluggish conversion of polysulfides to solid lithium sulfides limit the full utilization of active materials. Physical/chemical confinement is useful for anchoring polysulfides, but not effective for utilizing the blocked intermediates. Here, we employ black phosphorus quantum dots as electrocatalysts to overcome these issues. Both the experimental and theoretical results reveal that black phosphorus quantum dots effectively adsorb and catalyze polysulfide conversion. The activity is attributed to the numerous catalytically active sites on the edges of the quantum dots. In the presence of a small amount of black phosphorus quantum dots, the porous carbon/sulfur cathodes exhibit rapid reaction kinetics and no shuttling of polysulfides, enabling a low capacity fading rate (0.027% per cycle over 1000 cycles) and high areal capacities. Our findings demonstrate application of a metal-free quantum dot catalyst for high energy rechargeable batteries.
Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling
Authors: Zhang Yong , Sun Lihua , Xuan Lina , Pan Zhenwei , Hu Xueling , Liu Hongyu , Bai Yunlong , Jiao Lei , Li Zhange , Cui Lina , Wang Xiaoxue , Wang Siqi , Yu Tingting , Feng Bingbing , Guo Ying , Liu Zonghong , Meng Weixin , Ren Hequn , Zhu Jiyuan , Zhao Xuyun , Yang Chao , Zhang Ying , Xu Chaoqian , Wang Zhiguo , Lu Yanjie , Shan Hongli , Yang Baofeng 
Published: October 2018

AbstractLong non-coding RNAs (lncRNAs) have emerged as a new class of gene expression regulators playing key roles in many biological and pathophysiological processes. Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in patients with HF, and this downregulation slows cardiac conduction and enhances arrhythmogenicity. Moreover, CCRR silencing induces arrhythmias in healthy mice. CCRR overexpression eliminates these detrimental alterations. HF or CCRR knockdown causes destruction of intercalated discs and gap junctions to slow longitudinal cardiac conduction. CCRR overexpression improves cardiac conduction by blocking endocytic trafficking of connexin43 (Cx43) to prevent its degradation via binding to Cx43-interacting protein CIP85, whereas CCRR silence does the opposite. We identified the functional domain of CCRR, which can reproduce the functional roles and pertinent molecular events of full-length CCRR. Our study suggests CCRR replacement a potential therapeutic approach for pathological arrhythmias.
Cryo-EM structure of the hibernating Thermus thermophilus 100S ribosome reveals a protein-mediated dimerization mechanism
Authors: Flygaard Rasmus Kock , Boegholm Niels , Yusupov Marat , Jenner Lasse B. 
Published: October 2018

AbstractIn response to cellular stresses bacteria conserve energy by dimerization of ribosomes into inactive hibernating 100S ribosome particles. Ribosome dimerization in Thermus thermophilus is facilitated by hibernation-promoting factor (TtHPF). In this study we demonstrate high sensitivity of Tt100S formation to the levels of TtHPF and show that a 1:1 ratio leads to optimal dimerization. We report structures of the T. thermophilus 100S ribosome determined by cryo-electron microscopy to average resolutions of 4.13 Å and 4.57 Å. In addition, we present a 3.28 Å high-resolution cryo-EM reconstruction of a 70S ribosome from a hibernating ribosome dimer and reveal a role for the linker region connecting the TtHPF N- and C-terminal domains in translation inhibition by preventing Shine−Dalgarno duplex formation. Our work demonstrates that species-specific differences in the dimerization interface govern the overall conformation of the 100S ribosome particle and that for Thermus thermophilus no ribosome-ribosome interactions are involved in the interface.