bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Adversarial Autoencoders With Residual Dense Convolutional Networks for Estimation of Non‐Gaussian Hydraulic Conductivities
Authors: Mo Shaoxing , Zabaras Nicholas , Shi Xiaoqing , Wu Jichun
Published: January 2020

Inverse modeling for the estimation of non‐Gaussian hydraulic conductivity fields in subsurface flow and solute transport models remains a challenging problem. This is mainly due to the non‐Gaussian property, the nonlinear physics, and the fact that many repeated evaluations of the forward model are often required. In this study, we develop a convolutional adversarial autoencoder (CAAE) to parameterize non‐Gaussian conductivity fields with heterogeneous conductivity within each facies using a low‐dimensional latent representation. In addition, a deep residual dense convolutional network (DRDCN) is proposed for surrogate modeling of forward models with high‐dimensional and highly complex mappings. The two networks are both based on a multilevel residual learning architecture called residual‐in‐residual dense block. The multilevel residual learning strategy and the dense connection structure ease the training of deep networks, enabling us to efficiently build deeper networks that have an essentially increased capacity for approximating mappings of very high complexity. The CAAE and DRDCN networks are incorporated into an iterative ensemble smoother to formulate an inversion framework. The numerical experiments performed using 2‐D and 3‐D solute transport models illustrate the performance of the integrated method. The obtained results indicate that the CAAE is a robust parameterization method for non‐Gaussian conductivity fields with different heterogeneity patterns. The DRDCN is able to obtain accurate approximations of the forward models with high‐dimensional and highly complex mappings using relatively limited training data. The CAAE and DRDCN methods together significantly reduce the computation time required to achieve accurate inversion results.
Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning
Authors: Sala-Bayo Júlia , Fiddian Leanne , Nilsson Simon R. O. , Hervig Mona E. , McKenzie Colin , Mareschi Alexis , Boulos Maria , Zhukovsky Peter , Nicholson Janet , Dalley Jeffrey W. , Alsiö Johan , Robbins Trevor W.
Published: January 2020

Impaired cognitive flexibility in visual reversal-learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D2-like and D1-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual reversal learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of reversal learning as well as in the intermediate and late stages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial reversal-learning task. Reversal learning was improved after dopamine receptor blockade in the nucleus accumbens; the D1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively reduced early, perseverative errors. In contrast, reversal learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal striatum: raclopride increased errors in the intermediate phase after DMS infusions, and increased errors across phases after DLS infusions. These findings indicate that D1R and D2R modulate different stages of reversal learning through effects localised to different sub-regions of the striatum. Thus, deficits in behavioral flexibility observed in disorders linked to dopamine perturbations may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.
Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration
Authors: Beloueche-Babari Mounia , Casals Galobart Teresa , Delgado-Goni Teresa , Wantuch Slawomir , Parkes Harold G. , Tandy Debbie , Harker James A. , Leach Martin O.
Published: January 2020

Background

Monocarboxylate transporter 1 (MCT1) is a regulator of cell metabolism and a therapeutic target for cancer treatment. Understanding the changes in tumour function accompanying MCT1 inhibition will better characterise the anti-tumour effects of MCT1 inhibitors, potentially enabling the identification of pharmacodynamic biomarkers for the clinical development of these agents.

Methods

We assessed the impact of the MCT1 inhibitor AZD3965 on tumour metabolism and immune cell infiltration as key determinants of tumour biological function in the MCT1-dependent Raji B cell lymphoma model.

Results

Treatment of Raji xenograft-bearing severe combined immunodeficiency mice with AZD3965 led to inhibition of tumour growth paralleled with a decrease in tumour choline, as detected by non-invasive in vivo proton nuclear magnetic resonance spectroscopy. This effect was attributed to inhibition of phosphocholine de novo synthesis following decreased choline kinase α protein and messenger RNA expression that correlated with the AZD3965-induced build-up in intracellular lactate. These changes were concomitant with increased tumour immune cell infiltration involving dendritic and natural killer cells.

Conclusions

Our data provide new insights into the metabolic and cellular changes that occur in the tumour microenvironment following MCT1 blockade, which may contribute to the anti-tumour activity of AZD3965 and could have potential as pharmacodynamic biomarkers of MCT1 inhibition.
Improved early detection of ovarian cancer using longitudinal multimarker models
Authors: Whitwell Harry J. , Worthington Jenny , Blyuss Oleg , Gentry-Maharaj Aleksandra , Ryan Andy , Gunu Richard , Kalsi Jatinderpal , Menon Usha , Jacobs Ian , Zaikin Alexey , Timms John F.
Published: January 2020

Background

Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer.

Methods

This case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer.

Results

The best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time.

Conclusions

We have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.
Intratumoral heterogeneity and clonal evolution in liver cancer
Authors: Losic Bojan , Craig Amanda J. , Villacorta-Martin Carlos , Martins-Filho Sebastiao N. , Akers Nicholas , Chen Xintong , Ahsen Mehmet E. , von Felden Johann , Labgaa Ismail , DʹAvola Delia , Allette Kimaada , Lira Sergio A. , Furtado Glaucia C. , Garcia-Lezana Teresa , Restrepo Paula , Stueck Ashley , Ward Stephen C. , Fiel Maria I. , Hiotis Spiros P. , Gunasekaran Ganesh , Sia Daniela , Schadt Eric E. , Sebra Robert , Schwartz Myron , Llovet Josep M. , Thung Swan , Stolovitzky Gustavo , Villanueva Augusto
Published: January 2020

Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.
A compact single channel interferometer to study vortex beam propagation through scattering layers
Authors: Lathika Sruthy J. , Anand Vijayakumar , Bhattacharya Shanti
Published: January 2020

We propose and demonstrate a single channel interferometer that can be used to study how vortex beams propagate through a scatterer. The interferometer consists of a multifunctional diffractive optical element (MDOE) synthesized by the spatial random multiplexing of a Fresnel zone plate and a spiral Fresnel zone plate with different focal lengths. The MDOE generates two co-propagating beams, such that only the beam carrying orbital angular momentum is modulated by an annular stack of thin scatterers located at the focal plane of the Fresnel zone plate, while the other beam passes through the centre of the annulus without any modulation. The interference pattern is recorded at the focal plane of the spiral Fresnel zone plate. The scattering of vortex beams through stacks consisting of different number of thin scatterers was studied using the proposed optical setup. Conflicting results have been reported earlier on whether higher or lower charge beams suffer more deterioration. The proposed interferometer provides a relatively simple and compact means of experimentally studying propagation of vortex beams through scattering medium.
A multimodal neuroimaging classifier for alcohol dependence
Authors: Guggenmos Matthias , Schmack Katharina , Veer Ilya M. , Lett Tristram , Sekutowicz Maria , Sebold Miriam , Garbusow Maria , Sommer Christian , Wittchen Hans-Ulrich , Zimmermann Ulrich S. , Smolka Michael N. , Walter Henrik , Heinz Andreas , Sterzer Philipp
Published: January 2020

With progress in magnetic resonance imaging technology and a broader dissemination of state-of-the-art imaging facilities, the acquisition of multiple neuroimaging modalities is becoming increasingly feasible. One particular hope associated with multimodal neuroimaging is the development of reliable data-driven diagnostic classifiers for psychiatric disorders, yet previous studies have often failed to find a benefit of combining multiple modalities. As a psychiatric disorder with established neurobiological effects at several levels of description, alcohol dependence is particularly well-suited for multimodal classification. To this aim, we developed a multimodal classification scheme and applied it to a rich neuroimaging battery (structural, functional task-based and functional resting-state data) collected in a matched sample of alcohol-dependent patients (N = 119) and controls (N = 97). We found that our classification scheme yielded 79.3% diagnostic accuracy, which outperformed the strongest individual modality – grey-matter density – by 2.7%. We found that this moderate benefit of multimodal classification depended on a number of critical design choices: a procedure to select optimal modality-specific classifiers, a fine-grained ensemble prediction based on cross-modal weight matrices and continuous classifier decision values. We conclude that the combination of multiple neuroimaging modalities is able to moderately improve the accuracy of machine-learning-based diagnostic classification in alcohol dependence.
Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: a novel glycobiomarker for non-alcoholic steatohepatitis
Authors: Ogawa Koji , Kobayashi Takashi , Furukawa Jun-ichi , Hanamatsu Hisatoshi , Nakamura Akihisa , Suzuki Kazuharu , Kawagishi Naoki , Ohara Masatsugu , Umemura Machiko , Nakai Masato , Sho Takuya , Suda Goki , Morikawa Kenichi , Baba Masaru , Furuya Ken , Terashita Katsumi , Kobayashi Tomoe , Onodera Manabu , Horimoto Takahiro , Shinada Keisuke , Tsunematsu Seiji , Tsunematsu Izumi , Meguro Takashi , Mitsuhashi Tomoko , Hato Megumi , Higashino Kenichi , Shinohara Yasuro , Sakamoto Naoya
Published: January 2020

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may lead to liver cirrhosis or hepatocellular carcinoma. Here, we examined the diagnostic utility of tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin (AAT-A3F), a non-invasive glycobiomarker identified in a previous study of NASH diagnosis. This study included 131 biopsy-proven Japanese patients with NAFLD. We evaluated the utility of AAT-A3F in NASH diagnosis, and conducted genetic analysis to analyse the mechanism of AAT-A3F elevation in NASH. Serum AAT-A3F concentrations were significantly higher in NASH patients than in NAFL patients, and in patients with fibrosis, lobular inflammation, and ballooning. Hepatic FUT6 gene expression was significantly higher in NASH than in NAFL. IL-6 expression levels were significantly higher in NASH than in NAFL and showed a positive correlation with FUT6 expression levels. The serum-AAT-A3F levels strongly correlated with hepatic FUT6 expression levels. AAT-A3F levels increased with fibrosis, pathological inflammation, and ballooning in patients with NAFLD and may be useful for non-invasive diagnosis of NASH from the early stages of fibrosis.
Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats
Authors: Tsai Hui-Hsuan , Chen Chia-Wen , Yu Pei-Ling , Lin Yu-Ling , Hsieh Rong-Hong
Published: January 2020

Prostatic hyperplasia, characterized by progressive hyperplasia of glandular and stromal tissues, is the most common proliferative abnormality of the prostate in aging men. A high-fat diet (HFD) usually is a major factor inducing oxidative stress, inflammation, and an abnormal state of the prostate. Mangosteen pericarp powder (MPP) has abundant xanthones which can be antioxidant, anti-inflammatory, and antiproliferative agents. Therefore, the purpose of this study was to research whether MPP supplementation can affect the progression of prostatic hyperplasia. Twenty-four male F344 rats were randomly divided into four groups, including a control group (C), prostatic hyperplasia-induced group (P), prostatic hyperplasia-induced with low-dose MPP group (PL), and induced with high-dose MPP group (PH). The P, PL, and PH groups were given weekly intraperitoneal injections of 3,2′-dimethyl-4-aminobiphenyl (DMAB) at 25 mg/kg body weight for 10 weeks, and simultaneously fed an HFD for 24 weeks. Our findings first demonstrated that MPP consumption significantly decreased the prostate weight, serum testosterone and dihydrotestosterone concentrations, protein expression of proliferating cell nuclear antigen, and malondialdehyde levels and ameliorated mitochondrial function in prostatic tissues. These results suggest that MPP supplementation could be used to attenuate the progression of prostatic hyperplasia.
MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility
Authors: Calhoun Mark A. , Cui Yixiao , Elliott Eileen E. , Mo Xiaokui , Otero Jose J. , Winter Jessica O.
Published: January 2020

Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy). A prominent feature of the GBM microenvironment is compressive solid stress (CSS) caused by uninhibited tumor growth within the confined skull. Here, we utilized a mechanical compression model to apply CSS (<115 Pa) to well-characterized LN229 and U251 GBM cell lines and measured their motility, morphology, and transcriptomic response. Whereas both cell lines displayed a peak in migration at 23 Pa, cells displayed differential response to CSS with either minimal (i.e., U251) or large changes in motility (i.e., LN229). Increased migration of LN229 cells was also correlated to increased cell elongation. These changes were tied to epigenetic signaling associated with increased migration and decreases in proliferation predicted via Ingenuity® Pathway Analysis (IPA), characteristics associated with tumor aggressiveness. miRNA-mRNA interaction analysis revealed strong influence of the miR548 family (i.e., mir-548aj, mir-548az, mir-548t) on differential signaling induced by CSS, suggesting potential targets for pharmaceutical intervention that may improve patient outcomes.
Comparison of phenological traits, growth patterns, and seasonal dynamics of non-structural carbohydrate in Mediterranean tree crop species
Authors: Tixier Aude , Guzmán-Delgado Paula , Sperling Or , Amico Roxas Adele , Laca Emilio , Zwieniecki Maciej A.
Published: January 2020

Despite non-structural carbohydrate (NSC) importance for tree productivity and resilience, little is known about their seasonal regulations and trade-off with growth and reproduction. We characterize the seasonal dynamics of NSC in relation to the aboveground phenology and temporal growth patterns of three deciduous Mediterranean species: almond (Prunus dulcis (Mill.) D. A. Webb), walnut (Juglans regia L.) and pistachio (Pistacia vera L.). Seasonal dynamics of NSC were synchronous between wood tissues from trunk, branches and twigs. Almond had almost identical levels and patterns of NSC variation in twigs, branches and trunks whereas pistachio and walnut exhibited clear concentration differences among plant parts whereby twigs had the highest and most variable NSC concentration, followed by branches and then trunk. While phenology had a significant influence on NSC seasonal trends, there was no clear trade-off between NSC storage and growth suggesting that both were similarly strong sinks for NSC. A temporal trade-off observed at the seasonal scale was influenced by the phenology of the species. We propose that late senescing species experience C allocation trade-off at the end of the growing season because of C-limiting thermal conditions and priority allocation to storage in order to survive winter.
Comparison of laparoscopic and open pyloromyotomy: Concerns for omental herniation at port sites after the laparoscopic approach
Authors: van den Bunder Fenne A. I. M. , van Heurn Ernest , Derikx Joep P. M.
Published: January 2020

Pyloromyotomy is a common surgical procedure in infants with hypertrophic pyloric stenosis and can be performed with a small laparotomy or laparoscopically. No specific complications have been documented about one of the approaches. We aim to study (severity of) complications of pyloromyotomy and to compare complications of both approaches. Children undergoing pyloromyotomy between 2007 and 2017 were analyzed retrospectively. Complication severity was classified using the Clavien-Dindo classification. We included 474 infants (236 open; 238 laparoscopic). 401 were male (85%) and median (IQR) age was 33 (19) days. There were 83 surgical complications in 71 patients (15.0%). In the open group 45 infants (19.1%) experienced a complication vs. 26 infants in the laparoscopic group (10.5%)(p = 0.013). Severity and quantity of postoperative complications were comparable between both groups. Serosal tears of the stomach (N = 19) and fascial dehiscence (N = 8) occurred only after open pyloromyotomy. Herniation of omentum through a port site occurred only after laparoscopy (N = 6) and required re-intervention in all cases. In conclusion, the surgical complication rate of pyloromyotomy was 15.0%. Serosal tear of the stomach and fascial dehiscence are only present after open pyloromyotomy and omental herniation after laparoscopy respectively. The latter complication is underestimated and requires attention.
Landscape agricultural simplification correlates positively with the spatial distribution of a specialist yet negatively with a generalist pest
Authors: Dong Zhaoke , Zhang Qingqing , Li Lili , Lu Zengbin , Li Chao , Ouyang Fang , Tscharntke Teja , Yu Yi , Men Xingyuan
Published: January 2020

Agricultural expansion at the cost of natural or semi-natural habitats is simplifying human-dominated landscapes. As croplands provide a large resource of food to herbivores, pest damage may increase, but such large-scale patterns across regions are little known. Here, we used two years of maize field data from 102 counties (each 1318 km2 on average) across Shandong Province in China to study the spatial distribution of two major co-occurring maize pests: the putative habitat specialist the Asian Corn Borer (Ostrinia furnacalis) (ACB) and the generalist Yellow Peach Moth (Conogethes punctiferalis) (YPM). We used Spatial Analysis by Distance Indices (SADIE) to assess the spatial distribution patterns of these pests and their relation to landscape factors. In both 2016 and 2017, the aggregation and abundance of the ACB was positively correlated with the proportion of maize on the county level, whereas the YPM exhibited the opposite pattern, i.e., a negative correlation with maize proportion. The ACB abundance was below the economic threshold level when maize was <31% in 2017, whereas the YPM abundance was below the threshold when maize was >27% (in 2016) or 23% (in 2017). Maize plant presence was the main determinant of the abundance of the ACB, while the YPM appeared to benefit from further resources in non-crop habitats. These contrasting distribution patterns suggest that the two pests are driven by their different resource requirements. In more diversified landscapes, pest control may need to focus primarily on the generalist consumer, the YPM, whereas in maize-dominated landscapes, the specialist consumer, the ACB, is dominant and needs attention.
Dimensions of Impulsivity in Gambling Disorder
Authors: Mestre-Bach Gemma , Steward Trevor , Granero Roser , Fernández-Aranda Fernando , Mena-Moreno Teresa , Vintró-Alcaraz Cristina , Lozano-Madrid María , Menchón José M. , Potenza Marc N. , Jiménez-Murcia Susana
Published: January 2020

Impulsivity is a multidimensional construct. Although gambling disorder (GD) has been associated with high impulsivity, impulsivity across multiple domains has not been thoroughly investigated in this population. We first aimed to examine whether associations between three facets of impulsivity (response impulsivity, choice impulsivity and impulsive tendency) varied between GD patients and healthy controls (HC). We next aimed to evaluate relationships between these three types of impulsivity, as proposed by theoretical models of impulsivity, and their associations with GD severity. The sample included 97 treatment-seeking adult men with GD, diagnosed according to DSM-5 criteria, and 32 male HCs recruited from the general population. Greater impulsivity in all three domains was found in men with GD in comparison to men without GD. Associations between impulsivity facets were found in both groups, with response impulsivity being the only domain associated with GD severity. Our findings confirm that multiple domains of impulsivity are relevant in GD. Future studies should examine the extent to which treatments aimed at targeting specific aspects of impulsivity improve outcomes.
Quantification of Retinal Nerve Fibre Layer Thickness on Optical Coherence Tomography with a Deep Learning Segmentation-Free Approach
Authors: Mariottoni Eduardo B. , Jammal Alessandro A. , Urata Carla N. , Berchuck Samuel I. , Thompson Atalie C. , Estrela Tais , Medeiros Felipe A.
Published: January 2020

This study describes a segmentation-free deep learning (DL) algorithm for measuring retinal nerve fibre layer (RNFL) thickness on spectral-domain optical coherence tomography (SDOCT). The study included 25,285 B-scans from 1,338 eyes of 706 subjects. Training was done to predict RNFL thickness from raw unsegmented scans using conventional RNFL thickness measurements from good quality images as targets, forcing the DL algorithm to learn its own representation of RNFL. The algorithm was tested in three different sets: (1) images without segmentation errors or artefacts, (2) low-quality images with segmentation errors, and (3) images with other artefacts. In test set 1, segmentation-free RNFL predictions were highly correlated with conventional RNFL thickness (r = 0.983, P < 0.001). In test set 2, segmentation-free predictions had higher correlation with the best available estimate (tests with good quality taken in the same date) compared to those from the conventional algorithm (r = 0.972 vs. r = 0.829, respectively; P < 0.001). Segmentation-free predictions were also better in test set 3 (r = 0.940 vs. r = 0.640, P < 0.001). In conclusion, a novel segmentation-free algorithm to extract RNFL thickness performed similarly to the conventional method in good quality images and better in images with errors or other artefacts.
Excellent Combination of Tensile ductility and strength due to nanotwinning and a biamodal structure in cryorolled austenitic stainless steel
Authors: Kumar G. Venkata Sarath , Mangipudi K. R. , Sastry G. V. S. , Singh Lalit Kumar , Dhanasekaran S. , Sivaprasad K.
Published: January 2020

Austenitic stainless steels are prominent materials for their superior corrosion resistance and a combination of strength and ductility. However, the relatively low yield strength limits its application in high strength structural applications. Cryorolling is one of the promising methods of enhancing the mechanical properties of sheet metals. In the present work, Cryorolling of UNS S31000 stainless steel resulted in five-fold enhancement in yield strength with a significant loss in ductility. However, flash annealing at 800 °C for 120 s could restore its ductility up to 50% of its original ductility. The enhancement in strength is attributed to the formation of deformation nano-twins during flash annealing along with a bimodal grain structure.
Improved small blob detection in 3D images using jointly constrained deep learning and Hessian analysis
Authors: Xu Yanzhe , Wu Teresa , Gao Fei , Charlton Jennifer R. , Bennett Kevin M.
Published: January 2020

Imaging biomarkers are being rapidly developed for early diagnosis and staging of disease. The development of these biomarkers requires advances in both image acquisition and analysis. Detecting and segmenting objects from images are often the first steps in quantitative measurement of these biomarkers. The challenges of detecting objects in images, particularly small objects known as blobs, include low image resolution, image noise and overlap between the blobs. The Difference of Gaussian (DoG) detector has been used to overcome these challenges in blob detection. However, the DoG detector is susceptible to over-detection and must be refined for robust, reproducible detection in a wide range of medical images. In this research, we propose a joint constraint blob detector from U-Net, a deep learning model, and Hessian analysis, to overcome these problems and identify true blobs from noisy medical images. We evaluate this approach, UH-DoG, using a public 2D fluorescent dataset for cell nucleus detection and a 3D kidney magnetic resonance imaging dataset for glomerulus detection. We then compare this approach to methods in the literature. While comparable to the other four comparing methods on recall, the UH-DoG outperforms them on both precision and F-score.
Remodeling of the pulmonary artery in idiopathic pleuroparenchymal fibroelastosis
Authors: Kinoshita Yoshiaki , Ishii Hiroshi , Kushima Hisako , Johkoh Takeshi , Yabuuchi Hidetake , Fujita Masaki , Nabeshima Kazuki , Watanabe Kentaro
Published: January 2020

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonia that consists of alveolar septal elastosis and intra-alveolar collagenosis, which is predominantly located in the upper lobes. The aim of this study was to examine the remodeling of the pulmonary arteries in patients with IPPFE. This study included 18 patients with IPPFE, 24 patients with idiopathic pulmonary fibrosis (IPF), and 5 patients without pulmonary disease as controls. We selected muscular pulmonary arteries and calculated the percentage of the thickness of each layer of the wall (intima, media, and adventitia) in relation to the external diameter. We also quantified the percentage of areas of elastic fiber in the media divided by the whole area of the media (medial elastic fiber score). The percentage of adventitial thickness in IPPFE was significantly higher than that in IPF and in control lungs. The percentage of medial thickness did not differ statistically between IPPFE and IPF. However, the medial elastic fiber score in IPPFE was also significantly larger than that in IPF and control lungs. These results suggest that collagenous thickening of the adventitia and medial elastosis are distinct histological features in the muscular pulmonary arteries of patients with IPPFE.
Emergent features break the rules of crowding
Authors: Melnik Natalia , Coates Daniel R. , Sayim Bilge
Published: January 2020

Crowding is the deleterious influence of surrounding objects (flankers) on target identification. A central rule of crowding is that it is stronger when the target and the flankers are similar. Here, we show in three experiments how emergent features break this rule. Observers identified targets with various emergent features consisting of a pair of adjacent chevrons either pointing in opposite (‘Diamonds’ and ‘Xs’), or the same (both up or down) directions. Targets were flanked by Diamonds or Xs, resulting in conditions with different levels of target-flanker similarity. Despite high target-flanker similarity, Diamonds were identified better than Xs when flanked by Diamonds. Participants’ judgments of target conspicuity, however, showed that Diamonds were not perceived to stand out more strongly from X than Diamond flankers. Next, we asked observers to indicate whether all presented items were identical. We found superior performance with all Diamonds compared to all Xs, indicating that display uniformity judgments benefitted from the emergent features of Diamonds. Our results showed that emergent features and the information content of the entire display strongly modulated crowding. We suggest that conventional crowding rules only hold when target and flankers are artificially constrained to be mutually independent.
Recombinant Alkaline Phosphatase Prevents Acute on Chronic Liver Failure
Authors: Engelmann Cornelius , Adebayo Danielle , Oria Marc , De Chiara Francesco , Novelli Simone , Habtesion Abeba , Davies Nathan , Andreola Fausto , Jalan Rajiv
Published: January 2020

The lipopolysaccharide (LPS)– toll-like receptor-4 (TLR4) pathway plays an important role in liver failure. Recombinant alkaline phosphatase (recAP) deactivates LPS. The aim of this study was to determine whether recAP prevents the progression of acute and acute-on-chronic liver failure (ACLF). Eight groups of rats were studied 4-weeks after sham surgery or bile duct ligation and were injected with saline or LPS to mimic ACLF. Acute liver failure was induced with Galactosamine-LPS and in both models animals were treated with recAP prior to LPS administration. In the ACLF model, the severity of liver dysfunction and brain edema was attenuated by recAP, associated with reduction in cytokines, chemokines, liver cell death, and brain water. The activity of LPS was reduced by recAP. The treatment was not effective in acute liver failure. Hepatic TLR4 expression was reduced by recAP in ACLF but not acute liver failure. Increased sensitivity to endotoxins in cirrhosis is associated with upregulation of hepatic TLR4, which explains susceptibility to development of ACLF whereas acute liver failure is likely due to direct hepatoxicity. RecAP prevents multiple organ injury by reducing receptor expression and is a potential novel treatment option for prevention of ACLF but not acute liver failure.
Indel locations are determined by template polarity in highly efficient in vivo CRISPR/Cas9-mediated HDR in Atlantic salmon
Authors: Straume Anne Hege , Kjærner-Semb Erik , Ove Skaftnesmo Kai , Güralp Hilal , Kleppe Lene , Wargelius Anna , Edvardsen Rolf Brudvik
Published: January 2020

Precise gene editing such as CRISPR/Cas9-mediated homology directed repair (HDR) can increase our understanding of gene function and improve traits of importance for aquaculture. This fine-tuned technology has not been developed for farmed fish including Atlantic salmon. We performed knock-in (KI) of a FLAG element in the slc45a2 gene in salmon using sense (S), anti-sense (AS) and double-stranded (ds) oligodeoxynucleotide (ODN) templates with short (24/48/84 bp) homology arms. We show in vivo ODN integration in almost all the gene edited animals, and demonstrate perfect HDR rates up to 27% in individual F0 embryos, much higher than reported previously in any fish. HDR efficiency was dependent on template concentration, but not homology arm length. Analysis of imperfect HDR variants suggest that repair occurs by synthesis-dependent strand annealing (SDSA), as we show for the first time in any species that indel location is dependent on template polarity. Correct ODN polarity can be used to avoid 5′-indels interrupting the reading frame of an inserted sequence and be of importance for HDR template design in general.
Long-term Clinical Course after Vitrectomy for Breakthrough Vitreous Hemorrhage Secondary to Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy
Authors: Kim Jae Hui , Kim Jong Woo , Kim Chul Gu , Lee Dong Won
Published: January 2020

To investigate the long-term clinical course after vitrectomy for breakthrough vitreous hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). This retrospective study included 45 eyes that underwent vitrectomy due to breakthrough vitreous hemorrhage secondary to neovascular AMD. The patients were divided into 2 groups: neovascular AMD group and PCV group. Within each group, the status of the eye within 6 months after the surgery and that at the final follow-up was identified. The visual acuity at the final visit was additionally compared between the 2 groups. The patients were followed up for a mean period of 39.9 ± 19.4 months after the surgery. In the neovascular AMD group (n = 17), re-bleeding requiring vitrectomy was noted in 4 eyes and extensive scar formation was noted in 6 eyes within 6 months after the surgery. At the final visit, treatment was discontinued due to poor visual outcome in 10 eyes. In the PCV group (n = 28), re-bleeding requiring vitrectomy was noted in 1 eye, and extensive scar formation was noted in 4 eyes within 6 months after the surgery. At the final visit, treatment was discontinued in 8 eyes. The visual acuity at the final visit was significantly better in the PCV group (P = 0.003). The long-term clinical course after vitrectomy for breakthrough vitreous hemorrhage was markedly different between neovascular AMD and PCV, showing significantly better long-term visual outcomes in PCV.
Missing Link Prediction using Common Neighbor and Centrality based Parameterized Algorithm
Authors: Ahmad Iftikhar , Akhtar Muhammad Usman , Noor Salma , Shahnaz Ambreen
Published: January 2020

Real world complex networks are indirect representation of complex systems. They grow over time. These networks are fragmented and raucous in practice. An important concern about complex network is link prediction. Link prediction aims to determine the possibility of probable edges. The link prediction demand is often spotted in social networks for recommending new friends, and, in recommender systems for recommending new items (movies, gadgets etc) based on earlier shopping history. In this work, we propose a new link prediction algorithm namely “Common Neighbor and Centrality based Parameterized Algorithm” (CCPA) to suggest the formation of new links in complex networks. Using AUC (Area Under the receiver operating characteristic Curve) as evaluation criterion, we perform an extensive experimental evaluation of our proposed algorithm on eight real world data sets, and against eight benchmark algorithms. The results validate the improved performance of our proposed algorithm.
Clinical role of low hemoglobin ratio in poor neurologic outcomes in infants with traumatic intracranial hemorrhage
Authors: Lee En-Pei , Hsia Shao-Hsuan , Chan Oi-Wa , Lin Chia-Ying , Lin Jainn-Jim , Wu Han-Ping
Published: January 2020

Traumatic brain injury (TBI) is the leading cause of pediatric morbidity and mortality worldwide, and half of all fatalities occur in infants aged less than 1 year. We analyzed 129 infants diagnosed with TBI complicated with intracranial hemorrhage confirmed by brain computed tomography. We defined delta hemoglobin (ΔHB) as nadir HB - age specific mean HB, and the ratio of HB (%) as ΔHB/age specific mean HB x 100. Infants with poor neurologic outcomes had a lower admission HB and ΔHB (p < 0.05). The in-hospital mortality rate was 10.1% (13 infants), and the infants who died had a significantly lower ΔHB ratio compared to the survivors. The area under the receiving operating characteristic curve (AUC) of initial Glasgow Coma Score (GCS) in predicting neurologic outcomes was higher than that of ratio of ΔHB (0.881 v.s 0.859). In multivariate logistic regression analysis with the optimal cutoff ratio of ΔHB, it remained an independent predictor for in-hospital mortality and poor neurologic outcomes at discharge and at 6 months. AUC analysis for the ratio of ΔHB for poor neurologic outcomes in infants aged from 0–6 months was 0.85 and the optimal cutoff was −30.7% (sensitivity, 69%; specificity, 92%; positive likelihood ratio (LR+), 8.24; negative likelihood ratio (LR−), 0.34); the AUC was 0.88 in infants aged from 6–12 months and the optimal cutoff was −20.6% (sensitivity, 89%; specificity, 79%; LR+, 4.13; LR−, 0.15).
Molecular detection of free-living amoebae from Namhangang (southern Han River) in Korea
Authors: Kang Heekyoung , Sohn Hae-Jin , Seo Ga-Eun , Seong Gi-Sang , Ham A-Jeong , Park A-Young , Jung Suk-Yul , Lee Sang-Eun , Cho Shin-Hyeong , Shin Ho-Joon
Published: January 2020

The free-living amoebae Naegleria spp. and Acanthamoeba spp. exist in the natural environment and are sometimes causal agents of lethal primary amoebic meningoencephalitis (PAM), amoebic keratitis (AK) and granulomatous amebic encephalitis (GAE) in humans, respectively. To ascertain the existence of free-living amoebae in Korea, water samples were collected from the Korean hydrosphere, Namhangang (southern Han River), an active location for water skiing and recreation. Samples underwent two-step filtration and were cultured on non-nutrient agar medium with inactivated E. coli. The remaining samples were subjected to PCR for primarily the 18S small ribosomal RNA gene and gene sequencing. Similarities in 18S rDNA sequences, in comparison with various reference amoebae in GenBank, showed 86~99% homology with N. gruberi, N. philippinensis, N. clarki, A. polyphaga, A. castellannii, and Hartmannella (Vermamoeba) vermiformis. Therefore, this study will be useful for seasonal detection of free-living amoebae from various Korean hydrospheres in future studies.
Comparative analysis of pathophysiological parameters between emphysematous smokers and emphysematous patients with COPD
Authors: Bai Shuang , Ye Rui , Wang Cuihong , Sun Pengbo , Zhao Li
Published: January 2020

Emphysematous smokers with normal spirometry form a considerable proportion of the clinical population. However, despite presenting with respiratory symptoms and activity limitation, they cannot be diagnosed with chronic obstructive lung disease (COPD) according to current criteria. Thus, we aimed to determine whether emphysema in smokers has a different pathogenesis from that in patients with COPD. We compared 12 pairs of lung tissue samples from emphysematous patients with normal spirometry and COPD, and determined the degree of emphysema using computed tomography. With a focus on COPD-related pathogenesis, we independently assessed inflammatory response, protease-antiprotease balance, oxidative stress, and apoptosis in both groups. Both groups showed similar pathological changes at a comparable degree of emphysema; the expression of inflammatory factors was comparable, with overexpression of proteases and decreased levels of antiproteases. Moreover, there was no significant difference in the activities of glutathione and superoxide dismutase, and expression of apoptosis-related factors. In conclusion, emphysema in smokers with normal spirometry and in patients with COPD had similar pathogenesis. Forced expiratory volume in 1 second cannot be used as the sole diagnostic criterion in patients with COPD; early intervention is of great importance to such patients.
Author Correction: Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL
Authors: Epeldegui Marta , Conti David V. , Guo Yu , Cozen Wendy , Penichet Manuel L. , Martínez-Maza Otoniel
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Aeolian transport of viable microbial life across the Atacama Desert, Chile: Implications for Mars
Authors: Azua-Bustos Armando , González-Silva Carlos , Fernández-Martínez Miguel Ángel , Arenas-Fajardo Cristián , Fonseca Ricardo , Martín-Torres F. Javier , Fernández-Sampedro Maite , Fairén Alberto G. , Zorzano María-Paz
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Predicting the Dispersion Relations of One-Dimensional Phononic Crystals by Neural Networks
Authors: Liu Chen-Xu , Yu Gui-Lan
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Synergy of arbuscular mycorrhizal symbiosis and exogenous Ca2+ benefits peanut (Arachis hypogaea L.) growth through the shared hormone and flavonoid pathway
Authors: Cui Li , Guo Feng , Zhang Jialei , Yang Sha , Meng JingJing , Geng Yun , Li Xinguo , Wan Shubo
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Quantification of Water Flux in Vesicular Systems
Authors: Hannesschläger Christof , Barta Thomas , Siligan Christine , Horner Andreas
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling
Authors: Virumbrales-Muñoz María , Ayuso Jose M. , Lacueva Alodia , Randelovic Teodora , Livingston Megan K. , Beebe David J. , Oliván Sara , Pereboom Desirée , Doblare Manuel , Fernández Luis , Ochoa Ignacio
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Weight Bearing Activities change the Pivot Position after Total Knee Arthroplasty
Authors: Moewis Philippe , Hommel Hagen , Trepczynski Adam , Krahl Leonie , von Roth Philipp , Duda Georg N.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Valley phenomena in the candidate phase change material WSe2(1-x)Te2x
Authors: Oliver Sean M. , Young Joshua , Krylyuk Sergiy , Reinecke Thomas L. , Davydov Albert V. , Vora Patrick M.
Published: January 2020

Alloyed transition metal dichalcogenides provide an opportunity for coupling band engineering with valleytronic phenomena in an atomically-thin platform. However, valley properties in alloys remain largely unexplored. We investigate the valley degree of freedom in monolayer alloys of the phase change candidate material WSe2(1-x)Te2x. Low temperature Raman measurements track the alloy-induced transition from the semiconducting 1H phase of WSe2 to the semimetallic 1Td phase of WTe2. We correlate these observations with density functional theory calculations and identify new Raman modes from W-Te vibrations in the 1H-phase alloy. Photoluminescence measurements show ultra-low energy emission features that highlight alloy disorder arising from the large W-Te bond lengths. Interestingly, valley polarization and coherence in alloys survive at high Te compositions and are more robust against temperature than in WSe2. These findings illustrate the persistence of valley properties in alloys with highly dissimilar parent compounds and suggest band engineering can be utilized for valleytronic devices.
Spectroelectrochemistry, the future of visualizing electrode processes by hyphenating electrochemistry with spectroscopic techniques
Authors: Lozeman Jasper J. A. , Führer Pascal , Olthuis Wouter , Odijk Mathieu
Published: January 2020

Reviewing the future of electrochemistry combined with infrared, Raman, and nuclear magnetic resonance spectroscopy as well as mass spectrometry.
A ratiometric electrochemiluminescence method using a single luminophore of porous g-C3N4 for the ultrasensitive determination of alpha fetoprotein
Authors: Chen Lu , Wang Xuemei , Zhang Qiao , Li Zhe , Kang Qi , Shen Dazhong
Published: January 2020

In this work, we report a simple ratiometric electrochemiluminescence method for ultra-sensitive immunoanalysis.
Acetylcholinesterase-catalyzed silver deposition for ultrasensitive electrochemical biosensing of organophosphorus pesticides
Authors: Liu Zhenhui , Xia Xin , Zhou Guoxing , Ge Lei , Li Feng
Published: January 2020

This work reports, for the first time, acetylcholinesterase-catalyzed silver deposition for sensitive electrochemical detection of organophosphorus pesticides.
Electrochemical paper-based analytical devices: ten years of development
Authors: Ataide Vanessa N. , Mendes Letícia F. , Gama Lillia I. L. M. , de Araujo William R. , Paixão Thiago R. L. C.
Published: January 2020

The last decade saw the development of electrochemical paper-based analytical devices (ePADs).
Electrochemical biomolecule detection based on the regeneration of high-efficiency cascade catalysis for bifunctional nanozymes
Authors: Kou Beibei , Yuan Yali , Yuan Ruo , Chai Yaqin
Published: January 2020

Herein, the reusable high-efficiency cascade amplification of nanozymes was obtained for electrochemical analysis of 8-OHdG based on reversible capture/release of electronic media in a fast and green manner.
Bis[diphenylphosphino]methane and its bridge-substituted analogues as chemically non-innocent ligands for H2 activation
Authors: Kireev Nikolay V. , Filippov Oleg A. , Gulyaeva Ekaterina S. , Shubina Elena S. , Vendier Laure , Canac Yves , Sortais Jean-Baptiste , Lugan Noël , Valyaev Dmitry A.
Published: January 2020

Interconversion between coordinated diphosphinomethane and diphosphinomethanide moieties can be used as a new tool for metal–ligand cooperation.
Preparation of a graphene–phosphorene composite by pressure quenching and its ferromagnetism
Authors: Wu Yunpeng , Sun Qiushi , Yu Deyang , Teng Yifei , Liu Xilong , Feng Yi , Han Leiyun , Zhao Xudong , Liu Xiaoyang
Published: January 2020

A graphene–phosphorene composite was fabricated by a pressure quenching method in one step and it shows strong ferromagnetism.