bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryotoxicity of maternally transferred methylmercury to fathead minnows (Pimephales promelas)
Authors: Nielsen Kristin M. , Soulen Brianne K. , Overturf Carmen L. , Drevnick Paul E. , Roberts Aaron P.
Published: October 2015

Mercury (Hg) is a ubiquitous environmental contaminant and potent neurotoxin. In aquatic environments, Hg can be transformed into methylmercury (MeHg), which bioaccumulates in aquatic food webs, including fish. Methylmercury has been shown to transfer from female fish to developing eggs; however, relatively little is known regarding the effects of maternally transferred MeHg on fish embryos. The present study evaluated the effects of maternally transferred MeHg on fathead minnow (Pimephales promelas) embryos. Embryos were collected from adult fatheads exposed for 30 d to 1 of 3 diets spiked with MeHg: a control diet (0.02 ppm Hg dry wt), a low diet (0.87 ppm Hg dry wt), or a high diet (5.5 ppm Hg dry wt). No effects on spawning frequency, clutch size, or total egg output were observed. In embryos, Hg concentration was a function of female diet and the duration (number of days) of female exposure. Compared with controls, embryos from the low-diet treatment displayed altered embryonic movement patterns (hyperactivity) and decreased time to hatch. Embryos from the high-diet treatment had delayed hatching and increased mortality compared with the other treatments. Collectively, these results suggest that maternally transferred Hg may impact survival, behavior, and developmental milestones of the embryo-larval stages of fish. Environ Toxicol Chem 2016;35:1436–1441. © 2015 SETAC
Short-term toxicity of ammonia, nitrite, and nitrate to early life stages of the rare minnow (Gobiocypris rarus)
Authors: Luo Si , Wu Benli , Xiong Xiaoqin , Wang Jianwei
Published: October 2015

Nitrogenous pollutants including ammonia, nitrite, and nitrate are a widespread concern in natural waters and aquaculture. In the present study, the toxicity of ammonia, nitrite, and nitrate to rare minnow (Gobiocypris rarus) in the early life stage were evaluated by 2 short-term toxicity tests. In the short-term toxicity test, conducted on embryo and sac-fry stages, 30 fertilized eggs with 3 replicates were randomly exposed to varying levels of ammonia, nitrite, and nitrate until 3 d posthatch (dph). In the 7-d larval subchronic toxicity test, 30 newly hatched larvae with 3 replicates were randomly exposed to varying levels of ammonia, nitrite, and nitrate until 7 dph. The results showed that the 7-d larval subchronic toxicity test was more sensitive than the short-term toxicity test on embryo and sac-fry stages. Both toxicity tests revealed that ammonia was most toxic to rare minnows, followed by nitrite and nitrate. High levels of ammonia, nitrite, and nitrate decreased growth, retarded development, and increased mortality. The no-observed-effect concentrations of ammonia, nitrite, and nitrate for larval growth were 2.49 mg L−1, 13.33 mg L−1, and 19.95 mg L−1 nitrogen, respectively. The present study's results demonstrate that nitrogenous pollutants pose a threat to wild populations of rare minnows and provide useful information for establishing water quality criteria for this laboratory fish. Environ Toxicol Chem 2016;35:1422–1427. © 2015 SETAC
Effects of dietary exposure of polycyclic musk HHCB on the metamorphosis of Xenopus laevis
Authors: Pablos María Victoria , Jiménez María Ángeles , San Segundo Laura , Martini Federica , Beltrán Eulalia , Fernández Carlos
Published: October 2015

The compound 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[γ]-2-benzopyrane (HHCB; galaxolide, Chemical Abstracts Service number 1222-05-5) is a synthetic musk used extensively as a fragrance in many consumer products and classified as an emerging pollutant. The ecotoxicological information available for HHCB addresses exposure via water, but this compound is frequently adsorbed into particulate matter. The goal of the present study was to assess the effects of dietary exposure to several environmentally relevant HHCB concentrations adsorbed in food during Xenopus laevis metamorphosis. The authors sought to determine if such exposure to this synthetic musk resulted in histological changes in the thyroid gland in conjunction with changes in development (staging, timing to metamorphosis), body weight, and length. Developmental acceleration on day 14, together with hypertrophy of the thyroid follicular epithelium in tadpoles, suggested a possible agonistic effect of HHCB, which would have been compensated after metamorphosis by regulatory mechanisms to maintain homeostasis. Further research into the potential thyroid-related mechanisms of action of HHCB should be conducted. Environ Toxicol Chem 2016;35:1428–1435. © 2015 SETAC
Regulation of mechanosensitive biliary epithelial transport by the epithelial Na+ channel
Authors: Li Qin , Kresge Charles , Bugde Abhijit , Lamphere Michelle , Park Jason Y. , Feranchak Andrew P.
Published: October 2015

Intrahepatic biliary epithelial cells (BECs), also known as cholangiocytes, modulate the volume and composition of bile through the regulation of secretion and absorption. While mechanosensitive Cl– efflux has been identified as an important secretory pathway, the counterabsorptive pathways have not been identified. In other epithelial cells, the epithelial Na+ channel (ENaC) has been identified as an important contributor to fluid absorption; however, its expression and function in BECs have not been previously studied. Our studies revealed the presence of α, β, and γ ENaC subunits in human BECs and α and γ subunits in mouse BECs. In studies of confluent mouse BEC monolayers, the ENaC contributes to the volume of surface fluid at the apical membrane during constitutive conditions. Further, functional studies using whole‐cell patch clamp of single BECs demonstrated small constitutive Na+ currents, which increased significantly in response to fluid‐flow or shear. The magnitude of Na+ currents was proportional to the shear force, displayed inward rectification and a reversal potential of +40 mV (ENa+ = +60 mV), and were abolished with removal of extracellular Na+ (N‐methyl‐d‐glucamine) or in the presence of amiloride. Transfection with ENaCα small interfering RNA significantly inhibited flow‐stimulated Na+ currents, while overexpression of the α subunit significantly increased currents. ENaC‐mediated currents were positively regulated by proteases and negatively regulated by extracellular adenosine triphosphate. Conclusion: These studies represent the initial characterization of mechanosensitive Na+ currents activated by flow in biliary epithelium; understanding the role of mechanosensitive transport pathways may provide strategies to modulate the volume and composition of bile during cholestatic conditions. (Hepatology 2016;63:538–549)
The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential
Authors: Renaud Florence , Mariette Christophe , Vincent Audrey , Wacrenier Agnès , Maunoury Vincent , Leclerc Julie , Coppin Lucie , Crépin Michel , Van Seuningen Isabelle , Leteurtre Emmanuelle , Buisine Marie‐Pierre
Published: October 2015

The serrated neoplasia pathway accounts for 20–30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell‐rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP‐H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP‐H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway‐related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention.
Concerted actions of ameliorated colitis, aberrant crypt foci inhibition and 15‐hydroxyprostaglandin dehydrogenase induction by sonic hedgehog inhibitor led to prevention of colitis‐associated cancer
Authors: Kangwan Napapan , Kim Yoon‐Jae , Han Young‐Min , Jeong Migyeong , Park Jong‐Min , Hahm Ki‐Baik
Published: October 2015

The sonic hedgehog (Shh) signaling has been known to contribute to carcinogenesis in organ, where hedgehog exerted organogenesis and in cancers, which are developed based on mutagenic inflammation. Therefore, colitis‐associated cancer (CAC) can be a good model to prove whether Shh inhibitors can be applied to prevent, as the efforts to discover potent anti‐inflammatory agent are active to prevent CAC. Here, under the hypothesis that Shh inhibitors can prevent CAC, mouse model was generated to develop CAC by azoxymethane (AOM)‐initiated, dextran sodium sulfate–promoted carcinogenesis. Shh inhibitors, cerulenin and itraconazole were treated by oral gavage and the mice were sacrificed at early phase of 3 weeks and late phase of 16 weeks. Compared to control group, the number of aberrant crypt foci at 3 weeks and tumor incidence at 16 weeks were all significantly decreased with Shh inhibitor. Significant attenuations of macrophage infiltration accompanied with significant decreases of IL‐6, COX‐2, STAT3 and NF‐κB as well as significant ameliorations of β‐catenin nuclear translocation, cyclin D1 and CDK4 were imposed with Shh inhibitors. Especially, CAC was accompanied with significant cancellation of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH), but their levels were significantly preserved with Shh inhibitors. Among inflammatory mediators, significantly decreased levels of IL‐6 and TNF‐α, regulated with repressed NF‐κb and STAT3, were prominent with Shh inhibitor, whereas significant inductions of apoptosis were noted with Shh inhibitors. In conclusion, Shh inhibitors significantly prevented CAC covering either ameliorating oncogenic inflammation or suppressing tumor proliferation, especially supported with significant inhibition of IL‐6 and STAT3 signaling, 15‐PGDH preservation and apoptosis induction.
Interplay between self‐assembled structure of bone morphogenetic protein‐2 (BMP‐2) and osteoblast functions in three‐dimensional titanium alloy scaffolds: Stimulation of osteogenic activity
Authors: Nune K. C. , Kumar A. , Murr L. E. , Misra R. D. K.
Published: October 2015

Three‐dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three‐dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP‐2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self‐assembled dendritic microstructure with interconnected cellular‐type morphology of BMP‐2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2‐mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3‐ and 4‐mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP‐2 treated mesh structures, a behavior that is attributed to the unique self‐assembled structure of BMP‐2 that effectively communicates with the cells. The study underscores the potential of BMP‐2 in imparting osteoinductive capability to the 3D printed scaffolds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 517–532, 2016.
In vitro mineralization of MC3T3‐E1 osteoblast‐like cells on collagen/nano‐hydroxyapatite scaffolds coated carbon/carbon composites
Authors: Cao Sheng , Li Hejun , Li Kezhi , Lu Jinhua , Zhang Leilei
Published: October 2015

Collagen/nano‐hydroxyapatite (collagen/nHA) scaffolds were successfully prepared on carbon/carbon composites as bioactive films using the layer‐by‐layer coating method. Surface characterizations of collagen/nHA scaffolds were detected by scanning electron microscope (SEM), X‐ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Compressive strengths of the scaffolds were evaluated by a universal test machine. In vitro biological performances were determined using scaffolds seeded with MC3T3‐E1 osteoblasts‐like cells and cultured in mineralization medium for up to 21 days. In addition, cellular morphologies and several related gene expressions of MC3T3‐E1 cells in the scaffolds were also evaluated. Chemical and morphological analysis showed that the scaffolds had uniform pore sizes and unified phase composition. Mechanical testing indicated that the collagen/nHA scaffolds had the highest compressive strength in 50% of strain condition when the proportion of collagen and nano‐hydroxyapatite was 1:3. Cellular morphology observations and cytology tests indicated that MC3T3‐E1 cells were adhered on these scaffolds and proliferated. SEM photographs and gene expressions showed that mineralized MC3T3‐E1 cells and newly formed extra cellular matrix (ECM) filled up the pores of the scaffolds after the 3‐week mineralization inducement. Nano‐sized apatite particles were secreted from MC3T3‐E1 cells and combined with the reconstructed ECM. Collectively, collagen/nHA scaffolds provided C/C composites with a biomimetic surface for cell adhesion, proliferation and mineralized extra cellular matrices formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 533–543, 2016.
Molecular epidemiology is becoming complex under the dynamic HIV prevalence: The perspective from Harbin, China
Authors: Shao Bing , Song Bo , Cao Lijun , Du Juan , Sun Dongying , Lin Yuanlong , Wang Binyou , Wang Fuxiang , Wang Sunran
Published: October 2015

Unlike most areas of China, HIV transmission via men who have sex with men (MSM) is increasing rapidly, and has become the main route of HIV transmission in Harbin city. The purpose of the current study was to elaborate the molecular epidemiologic characteristics of the new HIV epidemic. Eighty‐one HIV‐1 gag gene sequences (HXB2:806–1861) from local HIV infections were isolated; CRF01_AE predominated among HIV infections (71.6%), followed by subtype B (16.5%), CRF07_BC (6.2%), and unique recombinant strains (URFs; 6.2%). URFs were most often identified in the MSM population, which consisted of a recombination of CRF01_AE with subtype B or CRF07_BC. Six clusters were formed in this analysis; clusters I and II mainly circulated in southwest China. Clusters III and IV mainly circulated in southwest, southeast, and central China. Clusters V and VI mainly circulated in north and northeast China. Clusters III and IV may facilitate the transmission of the CRF01_AE strain from the southwest to the north and northeast regions of China. HIV subtypes are becoming diverse with the persistent epidemic in this geographic region. In brief, our results indicate that the molecular epidemiology of HIV is trending to be more complex. Thus, timely molecular epidemiologic supervision of HIV is necessary, especially for the MSM population. J. Med. Virol. 88:807–814, 2016. © 2015 Wiley Periodicals, Inc.
Withaferin A suppresses the up‐regulation of acetyl‐coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model
Authors: Li Wenjuan , Zhang Chunjing , Du Hongyan , Huang Vincent , Sun Brandi , Harris John P. , Richardson Quitin , Shen Xinggui , Jin Rong , Li Guohong , Kevil Christopher G. , Gu Xin , Shi Runhua , Zhao Yunfeng
Published: October 2015

Withaferin A (WA), a natural product derived from Withania somnifera, has been used in traditional oriental medicines to treat neurological disorders. Recent studies have demonstrated that this compound may have a potential for cancer treatment and a clinical trial has been launched to test WA in treating melanoma. Herein, WA's chemopreventive potential was tested in a chemically‐induced skin carcinogenesis mouse model. Pathological examinations revealed that WA significantly suppressed skin tumor formation. Morphological observations of the skin tissues suggest that WA suppressed cell proliferation rather than inducing apoptosis during skin carcinogenesis. Antibody Micro array analysis demonstrated that WA blocked carcinogen‐induced up‐regulation of acetyl‐CoA carboxylase 1 (ACC1), which was further confirmed in a skin cell transformation model. Overexpression of ACC1 promoted whereas knockdown of ACC1 suppressed anchorage‐independent growth and oncogene activation of transformable skin cells. Further studies demonstrated that WA inhibited tumor promotor‐induced ACC1 gene transcription by suppressing the activation of activator protein 1. In melanoma cells, WA was also able to suppress the expression levels of ACC1. Finally, results using human skin cancer tissues confirmed the up‐regulation of ACC1 in tumors than adjacent normal tissues. In summary, our results suggest that withaferin A may have a potential in chemoprevention and ACC1 may serve as a critical target of WA. © 2015 Wiley Periodicals, Inc.
The condition of the least‐squares finite element matrices
Authors: Fried Isaac
Published: October 2015

A universal, practical, a priori, numerical procedure is presented by which to realistically bind the spectral condition number of the global stiffness matrix generated by the finite element least‐squares method. The procedure is then applied to second and fourth‐order problems in one and two dimensions to show that the condition of the global stiffness matrix thus generated is, in all instances, proportional to but the diameter of the element squared. Copyright © 2015 John Wiley & Sons, Ltd.
Prevalence of defined ultrasound findings of unknown significance at the second trimester fetal anomaly scan and their association with adverse pregnancy outcomes: the Welsh study of mothers and babies population‐based cohort
Authors: Hurt Lisa , Wright Melissa , Dunstan Frank , Thomas Susan , Brook Fiona , Morris Susan , Tucker David , Wills Marilyn Ann , Davies Colin , John Gareth , Fone David , Paranjothy Shantini
Published: October 2015

Objective

The aim of this article was to estimate the population prevalence of seven defined ultrasound findings of uncertain significance (‘markers’) in the second trimester and the associated risk of adverse pregnancy outcomes.

Method

A prospective record‐linked cohort study of 30 078 pregnant women who had second trimester anomaly scans between July 2008 and March 2011 in Wales was conducted.

Results

The prevalence of markers ranged from 43.7 per 1000 singleton pregnancies for cardiac echogenic foci [95% confidence interval (CI): 38.8, 51.1] to 0.6 for mild‐to‐moderate ventriculomegaly (95% CI: 0.3, 1.0). Isolated echogenic bowel was associated with an increased risk of congenital anomalies [risk ratio (RR) 4.54, 95% CI: 2.12, 9.73] and preterm birth (RR 2.30, 95% CI: 1.08, 4.90). Isolated pelvicalyceal dilatation was associated with an increased risk of congenital anomalies (RR 3.82, 95% CI: 2.16, 6.77). Multiple markers were associated with an increased risk of congenital anomalies (RR 5.00, 95% CI: 1.35, 18.40) and preterm birth (RR 3.38, 95% CI 1.20, 9.53).

Conclusions

These data are useful for counselling families and developing clinical guidance and care pathways following the detection of markers in clinical practice, particularly the need for follow‐up scans to monitor placental function and growth in pregnancies with isolated echogenic bowel, and further investigation for multiple markers. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
α‐exomethylene lactone possessing acetal–ester linkage: Polymerization and postpolymerization modification for water‐soluble polymer
Authors: Kohsaka Yasuhiro , Matsumoto Yusuke , Zhang Tianyi , Matsuhashi Yosuke , Kitayama Tatsuki
Published: October 2015

2,6‐Dimethyl‐5‐methylene‐1,3‐dioxa‐4‐one (DMDO), a cyclic acrylate possessing acetal–ester linkage, was obtained as a mixture of cis‐ and trans‐isomers (95:5) from Baylis–Hillman reaction of an aryl acrylate. The radical and anionic polymerizations of DMDO yielded the corresponding vinyl polymers without any side reactions such as cleavage of the acetal–ester linkage. The polymerization behaviors were significantly different from that of the acyclic acrylate, α‐(hydroxymethyl)acrylic acid, which was expected inactive against polymerization due to the steric hindrance around the vinylidene group by the α‐substituent. The acetal–ester linkage of the obtained polymer (P1) was completely cleaved via acid hydrolysis to afford a water soluble polymer, P2. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 955–961
Low‐thermal budget flash light annealing for Al2O3 surface passivation
Authors: Simon Daniel K. , Henke Thomas , Jordan Paul M. , Fengler Franz P. G. , Mikolajick Thomas , Bartha Johann W. , Dirnstorfer Ingo
Published: October 2015

This value is achieved due to a very low interface trap density of below 1010 eV–1 cm–2 and a fixed charge density of (2–3) × 1012 cm–2. In contrast, plasma ALD‐grown Al2O3 layers only reach carrier lifetimes of about 1 ms. This is mainly caused by a more than 10 times higher density of interface traps, and thus, inferior chemical passivation. The strong influence of the deposition parameters is explained by the limitation of hydrogen transport in Al2O3 during low‐thermal budget annealing. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Therapeutic potential of the endoplasmic reticulum located and secreted CDNF/MANF family of neurotrophic factors in Parkinson's disease
Authors: Voutilainen Merja H. , Arumäe Urmas , Airavaara Mikko , Saarma Mart
Published: October 2015

Parkinson's disease (PD) is a progressive neurodegenerative disorder where dopamine (DA) neurons in the substantia nigra degenerate and die. Since no cure for PD exists, there is a need for disease‐modifying drugs. Glial cell line‐derived neurotrophic factor (GDNF) and related neurturin (NRTN) can protect and repair DA neurons in neurotoxin animal models of PD. However, GDNF was unable to rescue DA neurons in an α‐synuclein model of PD, and both factors have shown modest effects in phase two clinical trials. Neurotrophic factors (NTFs), cerebral DA NTF (CDNF) and mesencephalic astrocyte‐derived NTF (MANF) form a novel family of evolutionarily conserved, endoplasmic reticulum (ER) located and secreted NTFs. CDNF and MANF have a unique structure and an unparalleled dual mode of action that differs from other known NTFs. Both protect cells from ER stress, and regulate the unfolded protein response via interacting with chaperons, and CDNF dissolves intracellular α‐synuclein aggregates. By binding to putative plasma membrane receptors, they promote the survival of DA neurons similarly to conventional NTFs. In animal models of PD, CDNF protects and repairs DA neurons, regulates ER stress, and improves motor function more efficiently than other NTFs.
Applications of Next-Generation Sequencing in Systemic Autoimmune Diseases
Authors: Ma Yiyangzi , Shi Na , Li Mengtao , Chen Fei , Niu Haitao
Published: October 2015

Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body’s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.
Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria
Authors: Shishido Tania K. , Jokela Jouni , Kolehmainen Clara-Theresia , Fewer David P. , Wahlsten Matti , Wang Hao , Rouhiainen Leo , Rizzi Ermanno , De Bellis Gianluca , Permi Perttu , Sivonen Kaarina
Published: October 2015

Significance

Cyclodextrins are cyclic oligosaccharides used in the pharmaceutical industry to improve drug delivery. Here, we show that cyclodextrins improve the antifungal activity of the anabaenolysins A and B lipopeptides and that are both produced by the same cyanobacteria. This study identifies the putative biosynthetic gene cluster involved in the synthesis of these unique cyanobacterial lipopeptide anabaenolysins.
Scalable clustering algorithms for continuous environmental flow cytometry
Authors: Hyrkas Jeremy , Clayton Sophie , Ribalet Francois , Halperin Daniel , Virginia Armbrust E. , Howe Bill
Published: October 2015

Motivation: Recent technological innovations in flow cytometry now allow oceanographers to collect high-frequency flow cytometry data from particles in aquatic environments on a scale far surpassing conventional flow cytometers. The SeaFlow cytometer continuously profiles microbial phytoplankton populations across thousands of kilometers of the surface ocean. The data streams produced by instruments such as SeaFlow challenge the traditional sample-by-sample approach in cytometric analysis and highlight the need for scalable clustering algorithms to extract population information from these large-scale, high-frequency flow cytometers.

Results: We explore how available algorithms commonly used for medical applications perform at classification of such a large-scale, environmental flow cytometry data. We apply large-scale Gaussian mixture models to massive datasets using Hadoop. This approach outperforms current state-of-the-art cytometry classification algorithms in accuracy and can be coupled with manual or automatic partitioning of data into homogeneous sections for further classification gains. We propose the Gaussian mixture model with partitioning approach for classification of large-scale, high-frequency flow cytometry data.

Availability and Implementation: Source code available for download at https://github.com/jhyrkas/seaflow_cluster, implemented in Java for use with Hadoop.

Contact: hyrkas@cs.washington.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Anaplastic astrocytoma and non-1p/19q co-deleted anaplastic oligoastrocytoma:
long-term survival, employment, and performance status of survivors
Authors: Pentsova Elena I. , Reiner Anne S. , Panageas Katherine S. , DeAngelis Lisa M.
Published: October 2015

Background

Despite optimal treatment for patients with anaplastic gliomas, median survival is 2 to 5 years, but some young adults survive longer. We sought to evaluate the functional and employment status of long-term survivors (5 years or more) diagnosed with anaplastic astrocytoma or non-1p/19q co-deleted anaplastic oligoastrocytoma.

Methods

We retrospectively identified patients with a diagnosis of anaplastic glioma at Memorial Sloan Kettering Cancer Center from 1999 to 2005. We reviewed demographics, pathology, 1p/19q status, survival, and treatment. Overall survival was estimated by the Kaplan-Meier method.

Results

There were 195 patients; 167 with anaplastic astrocytoma and 28 with anaplastic oligoastrocytoma. All patients were observed either to death or last follow-up. Sixty-four patients (33%) were identified as long-term survivors; 58% of these were men. The median age of the long-term survivors was 39 years and the median Karnofsky Performance Score was 100 at diagnosis. Thirteen patients underwent stereotactic biopsy, 7 had a gross total resection, and 44 a subtotal resection. Fifty-four patients completed radiation therapy as initial treatment; 54 received chemotherapy. Five years following diagnosis, median KPS was 90 and 55% of long-term survivors were employed and remained fully functional.

Conclusions

One-third of patients with non-co-deleted anaplastic glioma were long-term survivors, and more than one-half of long-term survivors resumed their prior level of employment and activity. However, a significant proportion could not return to normal function. These findings have serious implications for the social and financial status of these predominantly young adult survivors.
Systematic features of axisymmetric neutrino-driven core-collapse supernova models in multiple progenitors
Authors: Nakamura Ko , Takiwaki Tomoya , Kuroda Takami , Kotake Kei
Published: October 2015

We present an overview of two-dimensional (2D) core-collapse supernova simulations employing a neutrino transport scheme by the isotropic diffusion source approximation. We study 101 solar-metallicity, 247 ultra metal-poor, and 30 zero-metal progenitors covering zero-age main sequence mass from 10.8 M⊙ to 75.0 M⊙. Using the 378 progenitors in total, we systematically investigate how the differences in the structures of these multiple progenitors impact the hydrodynamics evolution. By following a long-term evolution over 1.0 s after bounce, most of the computed models exhibit neutrino-driven revival of the stalled bounce shock at ∼200–800 ms postbounce, leading to the possibility of explosion. Pushing the boundaries of expectations in previous one-dimensional studies, our results confirm that the compactness parameter ξ that characterizes the structure of the progenitors is also a key in 2D to diagnosing the properties of neutrino-driven explosions. Models with high ξ undergo high ram pressure from the accreting matter onto the stalled shock, which affects the subsequent evolution of the shock expansion and the mass of the protoneutron star under the influence of neutrino-driven convection and the standing accretion-shock instability. We show that the accretion luminosity becomes higher for models with high ξ, which makes the growth rate of the diagnostic explosion energy higher and the synthesized nickel mass bigger. We find that these explosion characteristics tend to show a monotonic increase as a function of the compactness parameter ξ.
Effects of the phencyclidine model of schizophrenia and nicotine on total and categorized ultrasonic vocalizations in rats
Authors: Swalve Natashia , Mulholland Michele M. , Schulz Tiffany D. , Li Ming
Published: October 2015

Patients with schizophrenia smoke cigarettes at a higher rate than the general population. We hypothesized that a factor in this comorbidity is sensitivity to the reinforcing and reinforcement-enhancement effects of nicotine. Phencyclidine (PCP) was used to model behavioral changes resembling negative symptoms of schizophrenia in rats. Ultrasonic vocalizations (USVs) in rats have been used to measure emotional states, with 50 kHz USVs indicating positive states and 22 kHz USVs indicating negative states. Total and categorized numbers of 22 and 50 kHz USVs and USVs during a visual stimulus (e.g. a potential measure of reinforcement-enhancement) were examined in rats following injection of PCP (2.0 mg/kg) and/or nicotine (0.2 or 0.4 mg/kg) daily for 7 days. PCP was then discontinued and all rats received nicotine (0.2 and 0.4 mg/kg) and PCP (2.0 mg/kg) on three challenge days. PCP acutely decreased 50 kHz vocalizations, whereas repeated nicotine potentiated rates of vocalizations, with similar patterns during light presentations. Rats in the PCP and nicotine combination groups made more 50 kHz vocalizations compared with rats in the control groups on challenge days. We conclude that PCP may produce a reward deficit, which is shown by decreased 50 kHz USVs, and behaviors post-PCP exposure may best model the comorbidity between schizophrenia and nicotine.
Pharmacotherapy for Depression Posttraumatic Brain Injury: A Meta-analysis
Authors: Salter Katherine L. , McClure J. Andrew , Foley Norine C. , Sequeira Keith , Teasell Robert W.
Published: October 2015

Objective:

To examine the effectiveness of pharmacotherapy for the treatment of depression following traumatic brain injury (TBI).

Design:

Systematic review and meta-analysis. Multiple electronic databases were searched to identify relevant studies examining effectiveness of pharmacotherapy for depression post-TBI. Clinical trials evaluating the use of pharmacotherapy in individuals with depression at baseline and using standardized assessments of depression were included. Data abstracted included sample size, antidepressant used, treatment timing/duration, method of assessment, and results pertaining to impact of treatment. Study quality was assessed using a modified Jadad scale.

Results:

Nine studies met criteria for inclusion. Pooled analyses based on reported means (standard deviations) from repeated assessments of depression showed that, over time, antidepressant treatment was associated with a significant effect in favor of treatment (Hedges g = 1.169; 95% confidence interval, 0.849-1.489; P < .001). Similarly, when limited to placebo-controlled trials, treatment was associated with a significant reduction in symptoms (standardized mean difference = 0.84; 95% confidence interval, 0.314-1.366; P = .002).

Conclusion:

Pharmacotherapy after TBI may be associated with a reduction in depressive symptomatology. Given limitations within the available literature, further well-powered, placebo-controlled trials should be conducted to confirm the effectiveness of antidepressant therapy in this population.
Evaluation of screening and brief intervention for hazardous alcohol use integrated into clinical practice in an inner-city Emergency Department
Authors: van Loon Merel , van Gaalen Angelique C.P. , van der Linden M. Christien , Hagestein-De Bruijn Carla
Published: October 2015

Introduction

In small studies, Screening, Brief Intervention and Referral to Treatment (SBIRT) in Emergency Departments (EDs) is effective in reducing hazardous alcohol use.

Objective

To examine the effectiveness of SBIRT at an inner-city ED in routine clinical practice.

Methods

Of the 41 900 consecutive ED patients aged 18 years and older, 22 537 (53.8%) were screened using the Alcohol Use Disorders Identification Test (AUDIT-C). Patients with positive AUDIT-C scores (men≥5 and women≥4) received educational leaflets. Brief interventions were performed by ED personnel trained in motivational interviewing. At 3 months, patients were contacted by telephone and recent drinking pattern was assessed.

Results

Out of 22 537 patients, 2209 (9.8%) had an elevated AUDIT-C score. Male sex, alcohol-related reason for ED visit, alcohol or other intoxication at ED visit, head injury, stomach or intestinal bleeding and wounds were significant predictors of hazardous alcohol use in both univariate and multivariate analysis (all P<0.001). Out of 2209 patients, 894 (40.5%) AUDIT-C-positive patients received an intervention: of these 894 patients, 70% received educational material and 30% received motivational intervention and educational material. In the subset of patients available for follow-up, 34.9% either reduced or stopped alcohol use.

Conclusion

Our study shows that in a large inner-city ED, SBIRT can be implemented in daily care. Screening uncovered large numbers of patients with hazardous alcohol use and identified several risk factors. Moreover, screening and intervention appeared to be effective in reducing alcohol intake.
Length of stay in emergency department and cerebral intravenous thrombolysis in community hospitals
Authors: Szczuchniak Wiktor , Kozera Grzegorz , Sobolewski Piotr , Brola Waldemar , Staszewski Jacek , Schminke Ulf , Nyka Walenty M.
Published: October 2015

Objectives

Current guidelines for the early management of patients with acute ischemic stroke recommend completion of an evaluation within 60 min of the patient’s arrival at the emergency department (ED) because prolongation of ED length of stay (LOS) may reduce the efficacy of acute stroke treatment.

Aim

To evaluate the LOS in EDs at the community-based Polish stroke centers, to determine logistic, social, epidemiological, and clinical factors responsible for its prolongation, and to assess the association between increased LOS and the implementation of cerebral intravenous (IV) thrombolysis.

Materials and methods

This study carried out an evaluation of the medical records of 8398 patients with stroke and transient ischemic attack who consecutively reported to the Pomeranian Stroke Registry from 2010 to 2012.

Results

The median ED LOS in the studied cohort was 97 (44–196) min and was prolonged (>60 min) in 63.1% of patients. Prolongation of ED LOS contributed to a low (4.9%) IV thrombolysis rate. Functional status at discharge was worse in patients with prolonged versus nonprolonged LOS [modified Rankin scale: 2 (0–3) vs. 1 (0–3) points; P<0.001]. Multivariate analysis showed that onset-to-door time more than 270 min or unknown time of symptoms onset, referral to ED in urban areas, living alone, presence of diabetes, motor, sensory, visual, and gait deficits at stroke onset, and NIHSS score on admission contributed toward prolongation of ED LOS.

Conclusion

A prolonged ED LOS, because of ineffective prehospital logistics, ED urban location, patients’ risk factors, and cohabitation profile and stroke symptoms and severity, commonly exists among patients with stroke and transient ischemic attack and contributes toward a low rate of IV thrombolysis in Polish community hospitals.
Time delay to surgery for appendicitis: no difference between surgical assessment unit and emergency department
Authors: Schultz Helen , Qvist Niels , Pedersen Birthe D. , Mogensen Christian B.
Published: October 2015

Background

In Denmark, emergency departments (EDs) are replacing acute surgical and medical units. The aim of this study was to compare the trajectory of patients undergoing surgery on the suspicion of appendicitis in a surgical assessment unit (SAU) and EDs with an observation unit, respectively. The primary outcome measure was the time from hospital arrival-to-decision for surgery.

Materials and methods

A comparative retrospective study with a cross-sectional design and a before-and-after design was carried out during January 2011 to December 2012 at a SAU and an ED at a university hospital (U-SAU and U-ED) and at an ED at a regional hospital (R-ED). Data included time of arrival, decision for surgery, surgery and discharge, and number of blood tests.

Results

In total, 250 patients were included. Time to decision for surgery was 4.50, 4.95, and 4.63 h (P=0.58) in the U-SAU, R-ED, and U-ED, respectively. Time from decision for surgery to start of surgery was 4.60, 3.29, and 4.12 h in the U-SAU, R-ED, and U-ED, respectively. The difference was significant between the U-SAU and R-ED (P=0.05) and between R-ED and U-ED (P=0.03). Time from surgery to discharge from the hospital was 17.88, 19.28, and 15.13 h in the U-SAU, R-ED, and U-ED, respectively. The difference was significant between the EDs (P=0.02). Significantly more blood tests were performed in the EDs than in the U-SAU.

Conclusion

The introduction of EDs with observation units did not influence time to decision for surgery, but more blood tests were performed.
Delivering Partner Services to Reduce Transmission and Promote Linkage to Care: Process Outcomes Varied for Chlamydial Infection, Gonorrhea, HIV, and Syphilis Cases
Authors: Martin Erika G. , Feng Wenhui , Qian Feng , Johnson Britney
Published: October 2015

Context:

Partner services for HIV and sexually transmitted diseases, a public health intervention activity recommended by the Centers for Disease Control and Prevention, includes counseling, partner notification, linkage to care, and referral to other services.

Objective:

A time study of partner services case investigations documented differences in times to process HIV/sexually transmitted disease cases.

Setting:

Cases were from 9 local and regional sites in New York.

Participants:

Fifty-two partner services disease investigators documented 542 randomly selected cases (271 chlamydial infections, 162 gonorrhea, 48 HIV, and 61 syphilis cases) assigned between June and September 2014. Cases were the unit of the analysis and represented 6.9% of all partner services investigations in 2014.

Design:

Cases were selected via stratified random sampling of infections assigned to staff. For each case, disease investigators completed a standard time study form to document the time spent on specific tasks and other outcomes. Kruskal-Wallis tests for continuous variables and χ2 tests for categorical variables assessed variation in outcomes across infection type.

Main Outcome Measures:

Outcomes included minutes spent on specific tasks (such as medical provider and index case outreach, travel, and partner notification), days the case remained open, disposition codes, and number of partners reached.

Results:

Case processing times varied, with HIV and syphilis tasks taking more minutes (P < .001) and cases staying open for more days (P < .001). Partners were notified in 33% of cases overall, with more notifications in syphilis (44%). Most time (median = 77%) was spent on index cases and 2% (median) on partner notification, with a wide range across cases.

Conclusions:

Given their chronic resource constraints, public health agencies must identify efficient methods to allocate resources, including which infections to prioritize. Documenting how workers allocate time across cases is essential to improving the effectiveness and efficiency of this program and generating the data to model return on investment.
Alicyclobacillus fodiniaquatilis sp. nov., isolated from acid mine water
Authors: Zhang Bo , Wu Yu-Fan , Song Jin-Long , Huang Zhong-Sheng , Wang Bao-Jun , Liu Shuang-Jiang , Jiang Cheng-Ying
Published: October 2015

Two novel, Gram-stain-variable, moderately thermophilic, acidophilic, rod-shaped, endospore-forming bacteria, G45-16T and G45-17, were isolated from acid mine water of Zijin copper mine in Fujian Province, China. Phylogenetic analysis of 16S rRNA gene sequences showed that they were closely related to Alicyclobacillus acidoterrestris ATCC 49025T with sequence similarities of 96.8 %. Cells grew aerobically at 20–45 °C (optimum, 40 °C), at pH 2.5–5.5 (optimum, pH 3.5) and in the presence of 0–4.0 % (w/v) NaCl. Strains contained MK-7 as the major menaquinone and the major cellular fatty acids were ω-cyclohexane C19 : 0 and ω-cyclohexane C17 : 0. The DNA G+C content was 51.3 and 49.8 mol% (T
m) for G45-16T and G45-17, respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons with their relatives and DNA–DNA relatedness values, it is concluded that strains G45-16T and G45-17 represent a novel species within the genus Alicyclobacillus, for which the name Alicyclobacillus fodiniaquatilis sp. nov. is proposed; the type strain is G45-16T ( = CGMCC 1.15049T = NBRC 111483T).
Contiguous and accuratede novoassembly of metazoan genomes with modest long read coverage
Authors: Chakraborty Mahul , Baldwin-Brown James G. , Long Anthony D. , Emerson J.J.
Published: October 2015

Genome assemblies that are accurate, complete, and contiguous are essential for identifying important structural and functional elements of genomes and for identifying genetic variation. Nevertheless, most recent genome assemblies remain incomplete and fragmented. While long molecule sequencing promises to deliver more complete genome assemblies with fewer gaps, concerns about error rates, low yields, stringent DNA requirements, and uncertainty about best practices may discourage many investigators from adopting this technology. Here, in conjunction with the platinum standardDrosophila melanogasterreference genome, we analyze recently published long molecule sequencing data to identify what governs completeness and contiguity of genome assemblies. We also present a hybrid meta-assembly approach that achieves remarkable assembly contiguity for both Drosophila and human assemblies with only modest long molecule sequencing coverage. Our results motivate a set of preliminary best practices for obtaining accurate and contiguous assemblies, a “missing manual” that guides key decisions in building high qualityde novogenome assemblies, from DNA isolation to polishing the assembly.
Blood circulation in the tunicateCorella inflata(Corellidae)
Authors: Konrad Michael W.
Published: October 2015

The ascidian tunicateCorella inflatais relatively transparent compared to other solitary tunicates and the circulatory system can be visualized by injecting high molecular weight fluorescein labeled dextran into the beating heart or the large vessels at the ends of the heart. In addition, after staining with neutral red the movement of blood cells can be followed to further define and characterize the circulatory system. The heart is a gently curved tube with a constriction in the middle and extends across the width of the animal. As in other tunicates, pumping is peristaltic and periodically reverses direction. During the abvisceral directional phase blood leaves the anterior end of the heart in two asymmetric vessels that connect to the two sides of the branchial basket (or pharynx), in contrast to the direct connection between the heart and the endostyle seen in the commonly studied tunicateCiona intestinalis.InCorella inflatablood then flows in both transverse directions through a complex system of ducts in the branchial basket into large ventral and dorsal vessels and then to the visceral organs in the posterior of the animal. During the advisceral phase blood leaves the posterior end of the heart in vessels that repeatedly bifurcate to fan into the stomach and gonads. Blood speed, determined by following individual cells, is high and pulsatory near the heart, but decreases and becomes more constant in peripheral regions. Estimated blood flow volume during one directional phase is greater than the total volume of the animal. Circulating blood cells are confined to vessels or ducts in the visible parts of the animal and retention of high molecular weight dextran in the vessels is comparable to that seen in vertebrates. These flow patterns are consistent with a closed circulatory network.
Structural characterization and low-temperature properties of Ru/C multilayer monochromators with different periodic thicknesses
Authors: Jiang Hui , He Yan , He Yumei , Li Aiguo , Wang Hua , Zheng Yi , Dong Zhaohui
Published: October 2015

Ru/C multilayer monochromators with different periodic thicknesses were investigated using X-ray grazing-incidence reflectivity, diffuse scattering, Bragg imaging, morphology testing,etc.before and after cryogenic cooling. Quantitative analyses enabled the determination of the key multilayer structural parameters for samples with different periodic thicknesses, especially the influence from the ruthenium crystallization. The results also reveal that the basic structures and reflection performance keep stable after cryogenic cooling. The low-temperature treatment smoothed the surfaces and interfaces and changed the growth characteristic to a low-frequency surface figure. This study helps with the understanding of the structure evolution of multilayer monochromators during cryogenic cooling and presents sufficient experimental proof for using cryogenically cooled multilayer monochromators in a high-thermal-load undulator beamline.