bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCOPE: a normalization and copy number estimation method for single-cell DNA sequencing
Authors: Wang Rujin , Lin Dan-Yu , Jiang Yuchao 
Published: March 2019

AbstractWhole genome single-cell DNA sequencing (scDNA-seq) enables characterization of copy number profiles at the cellular level. This technology circumvents the averaging effects associated with bulk-tissue sequencing and increases resolution while decreasing ambiguity in tracking the evolutionary history of cancer. ScDNA-seq data is, however, highly sparse and noisy due to the biases and artifacts that are introduced during the library preparation and sequencing procedure. Here, we propose SCOPE, a normalization and copy number estimation method for scDNA-seq data of cancer cells. The main features of SCOPE include: (i) a Poisson latent factor model for normalization, which borrows information across cells and regions to estimate bias, using negative control cells identified by cell-specific Gini coefficients; (ii) modeling of GC content bias using an expectation-maximization algorithm embedded in the normalization step, which accounts for the aberrant copy number changes that deviate from the null distributions; and (iii) a cross-sample segmentation procedure to identify breakpoints that are shared across cells from the same subclone. We evaluate SCOPE on a diverse set of scDNA-seq data in cancer genomics, using array-based calls of purified bulk samples as gold standards and whole-exome sequencing and single-cell RNA sequencing as orthogonal validations; we find that, compared to existing methods, SCOPE offers more accurate copy number estimates. Further, we demonstrate SCOPE on three recently released scDNA-seq datasets by 10X Genomics: we show that it can reliably recover 1% cancer cell spike-ins from a background of normal cells and that it successfully reconstructs cancer subclonal structure from ∼10,000 breast cancer cells.
A Bile Duct-on-a-Chip with Organ-Level Functions
Authors: Du Yu , Khandekar Gauri , Llewellyn Jessica , Polacheck William , Chen Christopher S. , Wells Rebecca G. 
Published: March 2019

AbstractChronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are frequently associated with damage to the barrier function of the biliary epithelium, but barrier function is difficult to study in vivo and has not been recapitulated in vitro. Here we report the development of a bile duct-on-a-chip that phenocopies not only the tubular architecture of the bile duct in three dimensions, but also its barrier functions. We demonstrated that mouse cholangiocytes in the channel of the device became polarized and formed mature tight junctions, and that the permeability of the cholangiocyte monolayer was comparable to that measured ex vivo for the rat bile duct. Permeability decreased significantly when cells formed a compacted monolayer with cell densities comparable to that seen in vivo. This device enabled independent access to the apical and basolateral surfaces of the cholangiocyte channel, allowing proof-of-concept toxicity studies with the biliary toxin biliatresone and the bile acid glycochenodeoxycholic acid. The cholangiocyte basolateral side was more vulnerable than the apical side to treatment with either agent, suggesting a protective adaptation of the apical surface that is normally exposed to bile. Further studies revealed a protective role of the cholangiocyte apical glycocalyx, wherein disruption of the glycocalyx with neuraminidase increased the permeability of the cholangiocyte monolayer after treatment with glycochenodeoxycholic acid. Conclusion: This bile duct-on-a-chip captured essential features of a simplified bile duct in structure and organ-level functions and represents a novel in vitro platform to study the pathophysiology of the bile duct using cholangiocytes from a variety of sources.
The application of oyster reefs in shoreline protection: Are we over‐engineering for an ecosystem engineer?
Authors: Morris Rebecca L. , Bilkovic Donna M. , Boswell Maura K. , Bushek David , Cebrian Just , Goff Joshua , Kibler Kelly M. , La Peyre Megan K. , McClenachan Giovanna , Moody Josh , Sacks Paul , Shinn Jenny P. , Sparks Eric L. , Temple Nigel A. , Walters Linda J. , Webb Bret M. , Swearer Stephen E. 
Published: March 2019

Abstract

Oyster reef living shorelines have been proposed as an effective alternative to traditional coastal defence structures (e.g. bulkheads, breakwaters), with the benefit that they may keep pace with sea‐level rise and provide co‐benefits, such as habitat provision. However, there remains uncertainty about the effectiveness of shoreline protection provided by oyster reefs, which limits their broader application.

We draw evidence from studies along the east and gulf coasts of the United States, where much research and implementation of oyster reef restoration has occurred, to better define the existing gaps in our understanding of the use of restored oyster reefs for shoreline protection.

We find potential disconnects between ecological and engineering functions of reefs. In response, we outline how engineering and ecological principles are used in the design of oyster reef living shorelines and highlight knowledge gaps where an integration of these disciplines will lead to their more effective application.

Synthesis and applications. This work highlights the necessary steps to advance the application of oyster reef living shorelines. Importantly, future research should focus on appropriate designs and conditions needed for these structures to effectively protect our coasts from erosion, while supporting a sustainable oyster population, thereby providing actionable nature‐based alternatives for coastal defence to diverse end‐users.
A nation‐wide survey of neonicotinoid insecticides in agricultural land with implications for agri‐environment schemes
Authors: Humann‐Guilleminot Ségolène , Binkowski Łukasz J. , Jenni Lukas , Hilke Gabriele , Glauser Gaétan , Helfenstein Fabrice 
Published: March 2019

Abstract

Neonicotinoids are the most widely used class of insecticides globally. However, the link between farming practices and the extent of contamination of soils and crops by neonicotinoid insecticides, as well as the extent of such contamination in organic fields and ecological focus areas (EFAs) are currently unclear.

We measured the concentrations of five neonicotinoid insecticides (imidacloprid, clothianidin, thiamethoxam, thiacloprid, acetamiprid) in 702 soil and plant samples in 169 cultivated fields and EFAs from 62 conventional, integrated production and organic farms distributed over the entire lowland of Switzerland.

We detected neonicotinoids in 93% of organic soils and crops, and more than 80% of EFA soils and plants—two types of arable land supposedly free of insecticides. We also tested 16 samples of organic seeds, of which 14 were positive for neonicotinoids.

Finally, we calculated hazard quotients (HQs) and potentially affected fractions for 72 beneficial and 12 pest species. Under a field‐realistic scenario, we found that between 5.3%–8.6% of above‐ground invertebrate species may be exposed to lethal concentrations of clothianidin, and 31.6%–41.2% to sublethal concentrations, in “integrated production” and conventional fields. We also found that 1.3%–6.8% (up to 12.5% based on HQs) of the beneficial invertebrate species may be exposed to sublethal concentrations of neonicotinoids in EFAs and organic fields. In contrast, no pest species would be exposed to lethal concentrations, even under a worst‐case scenario.

Synthesis and applications. Our study suggests that diffuse contamination by neonicotinoids may harm a significant fraction of non‐target beneficial species. The use of neonicotinoids on crops may threaten biodiversity in refuge areas, while also potentially jeopardizing the practice of organic farming by impeding the biological control of pests. On the basis of our results, we call for a reduction in the dispersion and overuse of neonicotinoid insecticides in order to prevent any detrimental effects on biodiversity and ecosystem services associated with agroecosystems.
The evolution of cleavage voting in four Western countries: Structural, behavioural or political dealignment?
Authors: GOLDBERG ANDREAS C. 
Published: March 2019

AbstractSince the heyday of cleavage voting in the 1960s and 1970s, the majority of studies presents evidence of a decline in cleavage voting – caused by either structural or behavioural dealignment. Structural dealignment denotes changes in group size responsible for a decrease in cleavage voting, whereas behavioural dealignment concerns weakening party–voter links over time. A third phenomenon posited in this article is the collective voting abstention of certain (social) groups, here referred to as ‘political dealignment’, which results in a new type of division of voting versus abstention. The purpose of this article is to examine the three underlying mechanisms for the decline in social class and religious cleavage voting across four Western countries (Great Britain, the Netherlands, Switzerland and the United States) over the last 40–60 years using longitudinal post‐election data. The results prove a strong presence of political dealignment and increasing turnout gaps regarding both the class and religious cleavage. Furthermore, whenever a decline in cleavage voting is present, it is mainly caused by changes in the social groups’ behaviour and less by changing social structures in a country.
Delay discounting and reward sensitivity in a 2 × 2 study of bipolar disorder and alcohol dependence
Authors: Mellick William , Tolliver Bryan K. , Brenner Helena , Prisciandaro James J. 
Published: March 2019

AbstractBackground and AimsSeparate studies have shown increased delay discounting in people with bipolar disorder (BD) and people with alcohol dependence (AD) relative to people without mental health problems. Delay discounting was compared in people with no mental health problems, AD, BD and AD plus BD. Associations of delay discounting with self‐reported impulsivity and reward sensitivity were also assessed.DesignThe study was a two‐by‐two factorial comparative observational design.SettingData were collected at baseline diagnostic visits as part of a neuroimaging study at a medical university in South Carolina, USA.ParticipantsTwenty‐two BD + AD, 33 BD, 28 AD and 27 people without mental health problems participated.MeasurementsDiagnostic and clinician‐rated symptom measures, self‐report questionnaires and a computerized delay discounting task were administered. Two‐by‐two general linear univariate models were tested to examine between‐group differences on discounting rates, and bivariate correlations and hierarchical regression analyses were performed to examine associations between discounting rates and self‐reported reward sensitivity and impulsivity.FindingsThere was a significant main effect of AD (P = 0.006, η2 = 0.068). The main effect of BD and the BD × AD interaction terms were non‐significant (P ≥ 0.293, η2 ≤ 0.010). Reward sensitivity and impulsivity were not significantly associated with discounting rates after adjustment for the other (P ≥ 0.089).ConclusionsPeople with alcohol dependence appear to have higher delay discounting, while previously found associations between bipolar disorder and delay discounting may be secondary to alcohol use disorder.
Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia
Authors: Choi Rihwa , Sohn Insuk , Kim Min‐Ji , Woo Hye In , Lee Ji Won , Ma Youngeun , Yi Eun Sang , Koo Hong Hoe , Lee Soo‐Youn 
Published: March 2019

AimsWe aimed to investigate the impact of various genetic polymorphisms affecting thiopurine metabolism pathways and toxicity in paediatric acute lymphoblastic leukaemia patients for the first time in Korea.MethodsFrom May 2006 to September 2016, 139 paediatric acute lymphoblastic leukaemia patients treated with combination chemotherapy including 6‐mercaptopurine were included in the study. One hundred and twenty‐three variants in 43 genes, includingTMPTandNUDT15, were screened using targeted genotyping, such as a MassARRAY system, direct sequencing and polymerase chain reaction‐restriction fragment length polymorphism methods. Among the polymorphisms screened, 103 polymorphisms of 43 genes were included for further analyses.ResultsThe genetic polymorphisms in theABCC4,AHCY,ATIC,FAM8A6P,GART,GNG2,GSTA1,MTHFD1,MTHFR,NUDT15,PACSIN2,TYMSandXDHgenes, and an intronic polymorphism betweenHIVEP2andAIG1, andTPMTgenotype were associated with thiopurine metabolism (P < 0.05). Genetic polymorphisms in theABCC4,ADK,ATIC,GART,GMPS,GSTP1,IMPDH1,ITPA,KCNMA1,MOCOS,MTRR,NUDT15,SLC19A1,SLC28A3,SLC29A1,SLCO1B1,TYMPandXDHgenes were associated with thiopurine‐related toxicities; neutropenia, hepatotoxicity and treatment interruption (P < 0.05).ConclusionsFindings of this study may provide basic knowledge for personalized medicine for thiopurinxe treatment in paediatric acute lymphoblastic leukaemia patients.
Children's Inferences About Friendship and Shared Preferences Based on Reported Information
Authors: Afshordi Narges 
Published: March 2019

Two experiments (total N = 195) examined third‐party inferences about friendship and shared preferences from reported dyadic information. Four‐year‐olds (N = 48) inferred friendship between individuals based on reports of prosocial behavior, and similarity, but not based on arbitrary links. Children privileged prosocial behavior over similarity when asked to adjudicate between the two. Adults (N = 120) were tested online and showed the same overall pattern of inferences. Furthermore, 4‐year‐olds (N = 27) expected individuals who had engaged in prosocial behavior to be playmates as well as friends, and to share preferences for novel games, but not novel foods. These findings shed crucial light on preschoolers' third‐party friendship inferences, and add to our knowledge of their concept of friendship.
The Influence of Direct and Overheard Messages on Children's Attitudes Toward Novel Social Groups
Authors: Lane Jonathan D. , Conder Emily B. , Rottman Joshua 
Published: March 2019

Individuals often develop negative biases toward unfamiliar or denigrated groups. Two experimental studies were conducted to investigate the extent to which brief negative messages about novel social groups influence children's (4‐ to 9‐year‐olds'; N = 153) intergroup attitudes. The studies examined the relative influence of messages that are provided directly to children versus messages that are overheard and examined whether the force of these messages varies with children's age. According to implicit and explicit measures of children's intergroup attitudes, children rapidly internalized messages demeaning novel groups, thus forming negative attitudes toward outgroups merely on the basis of hearsay. These effects were generally stronger among older children, and were particularly pronounced when the message was provided directly to children.
Not all abdominal masses after colorectal cancer surgery are malignant: intra‐abdominal fibromatosis masquerading as recurrence
Authors: Panagiotopoulou I. G. , Shah N. , Rowaiye B. , Chandrakumaran K. , Carr N. J. , Moran B. 
Published: March 2019

AbstractAimIntra‐abdominal fibromatosis is an unusual mesenchymal tumour that can be locally aggressive without any metastatic potential. Fibromatosis may simulate cancer recurrence on imaging surveillance for colorectal cancer follow‐up. The optimal treatment of recurrent peritoneal malignancy is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Confirmatory biopsy of lesions suspicious for colorectal cancer recurrence may not be feasible, thereby rendering surgery the safest option. Our aim was to determine the incidence of fibromatosis in a cohort of patients undergoing CRS and HIPEC for suspected colorectal cancer recurrence.MethodsOne hundred and seventy‐one CRS and HIPEC cases were performed at our Peritoneal Malignancy Institute between February 2007 and October 2018 for colorectal peritoneal metastases and were included in a prospectively maintained database.ResultsA total of 49 (29%) of 171 cases were performed for primary colorectal cancer with peritoneal metastases, whereas 122 (71%) of 171 cases were performed for suspected colorectal cancer recurrence detected on surveillance imaging after primary colorectal cancer resection. On histological analysis of the resected specimen, five (4.1%) of 122 cases undergoing CRS and HIPEC for colorectal recurrence had fibromatosis.ConclusionFibromatosis can masquerade as colorectal cancer recurrence. In this series it occurred with an incidence of 4.1% among a cohort of patients undergoing CRS and HIPEC for probable recurrence. Surgical resection may be the only option to confirm the diagnosis and rule out malignancy.
Eight autopsy cases of melanoma brain metastases showing angiotropism and pericytic mimicry. Implications for extravascular migratory metastasis
Authors: Rodewald Ann‐Katrin , Rushing Elisabeth J. , Kirschenbaum Daniel , Mangana Joanna , Mittmann Christiane , Moch Holger , Lugassy Claire , Barnhill Raymond L. , Mihic‐Probst Daniela 
Published: March 2019

AbstractBackgroundMetastatic tumor spread is a complex multistep process. Due to the blood‐brain barrier, metastasis to the central nervous system is restrictive with a distinct predilection for certain tumor types. In melanoma patients, brain metastasis is a common endpoint with the majority showing evidence of widespread disease at autopsy. In a previous murine melanoma model, we have shown that melanoma cells migrate along preexisting vessels into the brain, showing angiotropism/vascular co‐option and pericytic mimicry.MethodsUsing conventional morphology and immunohistochemistry, we analyze brain metastases from eight autopsy cases. In addition, tissue clearing, which enables three‐dimensional visualization over a distance of 100 μm is used.ResultsWe show the angiotropic localization of melanoma deposits in the brains in all eight autopsy cases. Tissue clearing techniques have allowed visualization of melanoma cells in one case exclusively along the abluminal surface of brain blood vessels over a distance of 100 μm, thus showing pericytic mimicry.ConclusionsOur analyses show clear‐cut evidence of angiotropism and pericytic mimicry of melanoma cells within the brain over some distance. In addition, these results support the hypothesis of metastasis along pathways other than hematogenous spread, or extravascular migratory metastasis (EVMM). During EVMM, melanoma cells may metastasize to the brain through pericytic mimicry, circumventing the blood‐brain barrier.
Adaptive working memory training can reduce anxiety and depression vulnerability in adolescents
Authors: Beloe Patricia , Derakshan Nazanin 
Published: March 2019

AbstractAdolescents can be at heightened risk for anxiety and depression, with accumulating research reporting on associations between anxiety and depression and cognitive impairments, implicating working memory and attentional control deficits. Several studies now point to the promise of adaptive working memory training to increase attentional control in depressed and anxious participants and reduce anxiety and depression symptoms, but this has not been explored in a non‐clinical adolescent population. The current study explored the effects of adaptive dual n‐back working memory training on sub‐clinical anxiety and depression symptomology in adolescents. Participants trained on either an online adaptive working memory task or non‐adaptive control task for up to 20 days. Primary outcome measures were self‐reported anxiety and depression symptomology, before and after intervention, and at 1‐month follow‐up. Self‐reported depression (p = 0.003) and anxiety (p = 0.04) decreased after training in the adaptive n‐back group relative to the non‐adaptive control group in the intention‐to‐treat sample (n = 120). These effects were sustained at follow‐up. Our findings constitute proof of principle evidence that working memory training may help reduce anxiety and depression vulnerability in a non‐clinical adolescent population. We discuss the findings’ implications for reducing risk of internalizing disorders in youth and the need for replication.
Does Autonomy Matter in State Owned Enterprises? Evidence from Performance Contracts in India
Authors: Gunasekar Sangeetha , Sarkar Jayati 
Published: March 2019

AbstractEmpirical evidence on the effect of managerial autonomy on the performance of state‐owned enterprises (SOE) is surprisingly scant despite autonomy being a preferred reform instrument over partial privatization in many countries. Using longitudinal data on performance contracts of state‐owned enterprises in India, this paper finds that managerial autonomy is associated with significant increases in enterprise profitability and efficiency. Further, using India's unique reform experience where both managerial autonomy and partial privatization were pursued side by side, the paper finds that while the positive effects of autonomy continue post‐partial privatization, the effects of partial privatization on performance are ambiguous. Specifically, once autonomy is controlled for, partial privatization has a positive effect on SOE profitability only after it crosses a critical level of government disinvestment. The findings suggest that organizational reforms such as granting managerial autonomy can be an important policy instrument in improving SOE performance particularly in cases where governments are unable to make substantial disinvestments.
Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement
Authors: Xu Mengting , Hua Yuyun , Qi Yan , Meng Guoliang , Yang Shengju 
Published: March 2019

AbstractHydrogen sulphide (H2S) is an important gasotransmitter with several physiological functions. However, the roles and the detailed mechanisms of H2S on skin wound healing are not known well. In the present study, 129S1/SvImJ mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for 2 weeks. Then, a round wound of 6 mm diameter with depth into the dermis was made. The skin wound area, blood perfusion, superoxide production, malondialdehyde (MDA) levels, total antioxidant capacity (T‐AOC), expression of vascular endothelial growth factor (VEGF), dynamin‐related protein 1 (DRP1) and optic atrophy 1 (OPA1) were measured. After NaHS (50 μmol/L) pre‐administration for 4 hours, cell migration rate, DRP1, OPA1 and α–smooth muscle actin (α‐SMA) expression, superoxide production and mitochondrial membrane potential in primary skin fibroblasts were measured. Tube formation in human umbilical vein endothelial cells (HUVECs) and cell migration in human keratinocytes were also measured. The results showed that NaHS pretreatment significantly accelerated wound healing and improved blood flow in the wound after operation. NaHS increased VEGF expression in the wound and promoted tube formation in HUVECs. Meanwhile, NaHS attenuated reactive oxygen species (ROS) production, suppressed MDA level but restored T‐AOC in the wound. NaHS also promoted skin fibroblasts migration and α‐SMA expression after scratch. Moreover, NaHS alleviated ROS, increased mitochondrial membrane potential, decreased DRP1 but enhanced OPA1 expression in skin fibroblasts after scratch. NaHS also accelerated human keratinocytes migration after scratch. Taken together, exogenous H2S supplementary accelerated the skin wound healing, which might be related to oxidative stress inhibition and VEGF enhancement.