bluuebunny/crossref_metadata_2025 huggingface dataset:
Syncytial Variant Nodular Sclerosis Classical Hodgkin Lymphoma in an Adolescent and Review of the Literature: A Unique Entity
Authors: Al-Antary Eman , Jesudas Rohith , George Amy , Poulik Janet , Savaşan Süreyya
Published: July 2018

Syncytial variant of nodular sclerosis (SV-NS) classical Hodgkin lymphoma (cHL) with its histologic features and clinical presentation is uncommon in adults and extremely rare in children. Here, we report a female teenager presenting with long-standing B symptoms, prominent soft tissue and bone involvement mimicking sarcoma and significant nodal disease who is diagnosed with advanced SV-NS cHL. Rare Reed-Sternberg-like cells displaying neutrophil and erythrocyte emperipolesis were seen on bone marrow aspiration slides. Despite initial complete response to chemotherapy and radiotherapy, the patient experienced early relapse suggestive of high-risk biology. This variant may constitute a unique entity.
Cardiac Surgery–Associated Kidney Injury in Children and Renal Oximetry
Authors: Joffe Rachel , Al Aklabi Mohammed , Bhattacharya Sudeshna , Cave Dominic , Calleja Thomas , Garros Daniel , Majesic Nicholas , Ryerson Lindsay , Morgan Catherine
Published: July 2018

Objectives:

Cardiac surgery–associated acute kidney injury is common in children and associates with negative outcomes. Novel interventions to reduce cardiac surgery–associated acute kidney injury require knowledge of its pathophysiology. States of altered perfusion, oxygen delivery, and energy consumption occur during cardiopulmonary bypass and could protect against or contribute to renal cellular injury and recovery. Near-infrared spectroscopy is noninvasive technology for monitoring regional blood flow and tissue oxygenation. This study evaluated the relationship between renal regional oxygen saturation and cardiac surgery–associated acute kidney injury, using near-infrared spectroscopy monitoring before, during, and after cardiopulmonary bypass in children.

Design:

Prospective cohort study.

Setting:

Single-center, tertiary care pediatric hospital (Stollery Children’s Hospital, Edmonton, AB, Canada).

Patients:

Children less than or equal to 10 kg undergoing congenital heart disease repair with cardiopulmonary bypass. Heart transplant, preoperative dialysis, sepsis, extracorporeal life support, congenital renal disease, and preoperative nephrotoxins were exclusions.

Interventions:

Renal regional near-infrared spectroscopy monitoring before, during, and after cardiopulmonary bypass.

Measurements and Main Results:

Outcome measure was cardiac surgery–associated acute kidney injury (defined according to Kidney Disease: Improving Global Outcomes criteria). Regional oxygen saturation was measured continuously using near-infrared spectroscopy (INVOS 5100C Cerebral/Somatic Oximeter; Medronic, Troy, MI) from time of anesthesia to time of transfer to intensive care. Cardiac surgery–associated acute kidney injury occurred in 65%. Lower baseline (precardiopulmonary bypass) regional oxygen saturation was associated with decreased risk of cardiac surgery–associated acute kidney injury (p = 0.01); children with baseline regional oxygen saturation in the highest tertile were 7.14 times more likely to get cardiac surgery– associated acute kidney injury (vs lowest tertile). Area under the curve for ability of baseline regional oxygen saturation to predict cardiac surgery–associated acute kidney injury was 0.73 (95% CI, 0.60–0.85). Children with lower baseline glomerular filtration rate had lower mean renal regional oxygen saturation.

Conclusions:

Findings demonstrate that preoperative oxygen supply/demand balance is an important predictor of cardiac surgery–associated acute kidney injury, suggesting lower preoperative (and intraoperative) renal blood flow may be protective. There is not yet a definite link between remote ischemic preconditioning and prevention of cardiac surgery–associated acute kidney injury; however, renal protective effects of sublethal ischemia should continue to be explored.
Improving Venous Thromboembolism Prophylaxis Administration in an Acute Surgical Unit
Authors: Allaway Matthew G. R. , Eslick Guy D. , Kwok Grace T. Y. , Cox Michael R.
Published: July 2018

Objectives

Venous thromboembolism (VTE) prophylaxis regimes frequently have a wide variation in application. Nepean acute surgical unit was established in 2006 as a novel model for emergency surgical care. As part of the model’s rollout, there were several areas of clinical management targeted for improvement, one being VTE prophylaxis compliance. It was decided all patients older than 18 years treated for a variety of acute surgical conditions within the acute surgical unit should be administered routine VTE prophylaxis with heparin and compression stockings. A novel multifaceted intervention was implemented at the time to achieve this goal. The primary aim of this study was to determine VTE prophylaxis administration rates before and after this intervention.

Methods

A before-after study conducted as a retrospective review of medical records of all patients 18 years or older, having an appendicectomy in 3 periods: Before acute surgical unit (ASU) (November 2004 to October 2006), Early ASU (November 2006 to October 2008), and Established ASU (January 2012 to December 2013). Outcomes were mechanical and pharmacological VTE prophylaxis administration rates for each group.

Results

There were 1149 patients included in the study: Before ASU, 167; Early ASU, 375; and Established ASU, 607. There was a significant stepwise increase in parmacological VTE prophylaxis administration: Before ASU, 54.5%; Early ASU, 74.7%; and Established ASU, 96.9% (Before versus Early: odds ratio [OR], 2.46; 95% confidence interval [CI], 1.68–3.61; P < 0.001; Early versus Established: OR, 10.500; 95% CI, 6.29–17.53; P < 0.001). Mechanical VTE prophylaxis was significantly increased in the established group (Before versus Established: OR, 47.18; 95% CI, 25.61–86.91; P < 0.001).

Conclusions

There was a significant increase in VTE prophylaxis administration after the implementation of our multifaceted intervention. Allocating a responsible provider dedicated to VTE prophylaxis prescription and compliance checking was a key component to this intervention.
Development of a Clinical Decision Support System for Living Kidney Donor Assessment Based on National Guidelines
Authors: Knight Simon R. , Cao Khoa N. , South Matthew , Hayward Nicki , Hunter James P. , Fox John
Published: July 2018

Background

Live donor nephrectomy is an operation that places the donor at risk of complications without the possibility of medical benefit. Rigorous donor selection and assessment is therefore essential to ensure minimization of risk and for this reason robust national guidelines exist. Previous studies have demonstrated poor adherence to donor guidelines.

Methods

We developed a clinical decision support system (CDSS), based on national living donor guidelines, to facilitate the identification of contraindications, additional investigations, special considerations, and the decision as to nephrectomy side in potential living donors. The CDSS was then tested with patient data from 45 potential kidney donors.

Results

The CDSS comprises 17 core tasks completed by either patient or nurse, and 17 optional tasks that are triggered by certain patient demographics or conditions. Decision rules were able to identify contraindications, additional investigations, special considerations, and predicted operation side in our patient cohort. Seventeen of 45 patients went on to donate a kidney, of whom 7 had major contraindications defined in the national guidelines, many of which were not identified by the clinical team. Only 43% of additional investigations recommended by national guidelines were completed, with the most frequently missed investigations being oral glucose tolerance testing and routine cancer screening.

Conclusions

We have demonstrated the feasibility of turning a complex set of national guidelines into an easy-to-use machine-readable CDSS. Comparison with real-world decisions suggests that use of this CDSS may improve compliance with guidelines and informed consent tailored to individual patient risks.
Tailoring 3D cell culture templates with common hydrogels
Authors: Pasturel Aurélien , Strale Pierre-Olivier , Studer Vincent
Published: July 2018

3D cell culture aims at reconciliating the simplicity of in vitro models with the human like properties encountered in vivo. Soft permeable hydrogels have emerged as user-friendly materials to grow cells in more physiological conditions. With the intent on turning these homogeneous substrates into biomimetic templates, we introduce a generic solution compatible with the most biologically relevant and often frail materials. Here we take control of the chemical environment driving generic radical reactions to craft common gels with patterned light. In a simple microreactor, we harness the well-known inhibition of radicals by oxygen to enable topographical photopolymerization. Strikingly, by sustaining an oxygen rich environment, we can also induce hydrogel photo-scission which turns out to be a powerful and generic subtractive manufacturing method. We finally introduce a flexible patterned functionalization protocol based on available photo-linkers. Using these common tools on the most popular hydrogels, we tailored soft templates where cells grow or self-organize into standardized structures. The platform we describe has the potential to set a standard in future 3D cell culture experiments.
Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty
Authors: Sekine Ryoji , Shibata Tatsuo , Ebisuya Miki
Published: July 2018

Pattern formation is fundamental for embryonic development. Although synthetic biologists have created several patterns, a synthetic mammalian reaction-diffusion pattern has yet to be realized. TGF-β family proteins Nodal and Lefty have been proposed to meet the conditions for reaction-diffusion patterning: Nodal is a short-range activator that enhances the expression of Nodal and Lefty whereas Lefty acts as a long-range inhibitor against Nodal. However, the pattern forming possibility of the Nodal-Lefty signaling has never been directly tested, and the underlying mechanisms of differential diffusivity of Nodal and Lefty remain unclear. Here, through a combination of synthetic biology and theoretical modeling, we show that a reconstituted minimal network of the Nodal-Lefty signaling spontaneously gives rise to a pattern in mammalian cell culture. Surprisingly, extracellular Nodal was confined underneath the cells as small clusters, resulting in a narrow distribution range compared with Lefty. We further found that the finger 1 domain of the Nodal protein is responsible for its short-range distribution. By transplanting the finger 1 domain of Nodal into Lefty, we converted the originally long-range distribution of Lefty to a short-range one, successfully preventing the pattern formation. These results indicate that the differences in the localization and domain structures between Nodal and Lefty, combined with the activator-inhibitor topology, are sufficient for reaction-diffusion pattern formation in mammalian cells.
Crispr/Cas9 Targeted Capture of Mammalian Genomic Regions for Characterization by NGS
Authors: Slesarev Alexei , Viswanathan Lakshmi , Tang Yitao , Borgschulte Trissa , Achtien Katherine , Razafsky David , Onions David , Chang Audrey , Cote Colette
Published: July 2018

The robust detection of structural variants in mammalian genomes remains a challenge. It is particularly difficult in the case of genetically unstable Chinese hamster ovary (CHO) cell lines with only draft genome assemblies available. We explore the potential of the CRISPR/Cas9 system for the targeted capture of genomic loci containing integrated vectors in CHO-K1-based cell lines, and compare it to popular target-enrichment methods and to whole genome sequencing (WGS). The CRISPR/Cas9-based techniques allow for amplification-free capture of genomic regions, which reduces the possibility of sequencing artifacts. Other advantages of these methods are the ease of bioinformatics analysis, potential for multiplexing, and the production of longer sequencing templates for real-time sequencing. The utility of these protocols has been proven by identification of transgene integration sites and flanking sequences in a number of CHO cell lines. However, data produced by these and other targeted capture methods are not always sufficient to analyze complex genomic rearrangements (CGRs) or unexpected sequences introduced into genome by vector integration events. In contrast, WGS provides complete information about vector integration sites, vector copy number, CGRs, and foreign DNA-but despite these benefits, WGS is not easily implemented due to the cost and complexity of the analysis.
Q-FADD: A mechanistic approach for modeling the accumulation of proteins at sites of DNA damage by free diffusion
Authors: Mahadevan Jyothi , Rudolph Johannes , Jha Asmita , Tay Jian Wei , Dragavon Joe , Grumstrup Erik M. , Luger Karolin
Published: July 2018

The repair of DNA damage requires the ordered recruitment of many different proteins that are responsible for signaling and subsequent repair. A powerful tool for studying the orchestrated accumulation of these proteins at damage sites is laser microirradiation in live cells, followed by monitoring of the accumulation of the fluorescently labeled protein in question. Despite the widespread use of this approach, there exists no rigorous method for characterizing this process quantitatively. Here we introduce a free diffusion model that explicitly accounts for the unique topology of individual nuclei and quantitatively describes the accumulation of two test proteins, poly-ADP-ribose polymerases 1 and 2. Application of our model to other proteins will yield novel insights into the timing and mechanism of DNA repair.
Response to early drought stress and identification of QTLs controlling biomass production under drought in pearl millet
Authors: Debieu M , Sine B , Passot S , Grondin A , Akata AE , Gangashetty P , Vadez V , Gantet P , Foncéka D , Cournac L , Hash CT , Kane NA , Vigouroux Y , Laplaze L
Published: July 2018

Pearl millet plays a major role in food security in arid and semi-arid areas of Africa and India. However, it lags behind the other cereal crops in terms of genetic improvement. The recent sequencing of its genome opens the way to the use of modern genomic tools for breeding. Our study aimed at identifying genetic components involved in early drought stress tolerance as a first step toward the development of improved pearl millet varieties or hybrids. A panel of 188 inbred lines from West Africa was phenotyped under early drought stress and well-irrigated conditions. We found a strong impact of drought stress on yield components. This impact was variable between inbred lines. We then performed an association analysis with a total of 392,493 SNPs identified using Genotyping-by-Sequencing (GBS). Correcting for genetic relatedness, genome wide association study identified QTLs for biomass production in early drought stress conditions and for stay-green trait. In particular, genes involved in the sirohaem and wax biosynthesis pathways were found to co-locate with association loci. Our results open the way to use genomic selection to breed pearl millet lines with improved yield under drought stress.
Thecis-regulatory logic underlying abdominal Hox-mediated repression versus activation of regulatory elements inDrosophila
Authors: Zandvakili Arya , Uhl Juli , Campbell Ian , Song Yuntao Charlie , Gebelein Brian
Published: July 2018

Hox genes encode a family of transcription factors that, despite having similarin vitroDNA binding preferences, regulate distinct genetic programs along the metazoan anterior-posterior axis. To better define mechanisms of Hox specificity, we compared and contrasted the ability of abdominal Hox factors to regulate twocis-regulatory elements within theDrosophilaembryo. Both the Ultrabithorax (Ubx) and Abdominal-A (Abd-A) Hox factors form cooperative complexes with the Extradenticle (Exd) and Homothorax (Hth) transcription factors to repress thedistal-lessleg selector gene via theDCRE, whereas only Abd-A interacts with Exd and Hth on theRhoAelement to activate arhomboidserine protease gene that stimulates Epidermal Growth Factor secretion. By swapping binding sites between these elements, we found that theRhoAExd/Hth/Hox site configuration that mediates Abd-A specific activation can also convey transcriptional repression by both Ubx and Abd-A when placed into theDCRE,but only in one orientation. We further show that the orientation and spacing of Hox sites relative to additional transcription factor binding sites within theRhoAandDCREelements is critical to mediate appropriate cell- and segment-specific output. These results indicate that the interaction between Hox, Exd, and Hth neither determines activation vs repression specificity nor defines Ubx vs Abd-A specificity. Instead the precise integration of Hox sites with additional TF inputs is required for accurate transcriptional output. Taken together, these studies provide new insight into the mechanisms of Hox target and regulatory specificity as well as the constraints placed on regulatory elements to convey appropriate outputs.

Author Summary

The Hox genes encode a family of transcription factors that give cells within each region along the developing body plan a unique identity in animals from worms to mammals. Surprisingly, however, most of the Hox factors bind the same or highly similar DNA sequences. These findings raise a paradox: How can proteins that have highly similar DNA binding properties perform different functions in the animal by regulating different sets of target genes? In this study, we address this question by studying how two Hox factors regulate the expression of target genes that specify leg development and the making of liver-like cells in the developing fly. By comparing and contrasting how Hox target genes are activated and/or repressed, we found that the same Hox binding sites can mediate either activation or repression in a manner that depends upon context. In addition, we found that a Hox binding site that is normally regulated by only one Hox factor, can also be used by more than one Hox factor swapped into another target gene. These findings indicate that the specificity of a Hox factor to regulate target genes does not rely solely upon DNA binding specificity but also requires regulatory specificity.
Is it possible to reconstruct an accurate cell lineage using CRISPR recorders?
Authors: Salvador-Martínez Irepan , Grillo Marco , Averof Michalis , Telford Maximilian J.
Published: July 2018

Cell lineages provide the framework for understanding how multicellular organisms are built and how cell fates are decided during development. Describing cell lineages in most organisms is challenging, given the number of cells involved; even a fruit fly larva has ~50,000 cells and a small mammal has more than 1 billion cells. Recently, the idea of using CRISPR to induce mutations during development as heritable markers for lineage reconstruction has been proposed and trialled by several groups. While an attractive idea, its practical value depends on the accuracy of the cell lineages that can be generated by this method. Here, we use computer simulations to estimate the performance of this approach under different conditions. Our simulations incorporate empirical data on CRISPR-induced mutation frequencies inDrosophila. We show significant impacts from multiple biological and technical parameters - variable cell division rates, skewed mutational outcomes, target dropouts and different mutation sequencing strategies. Our approach reveals the limitations of recently published CRISPR recorders, and indicates how future implementations can be optimised to produce accurate cell lineages.
Signalling pathways drive heterogeneity of ground state pluripotency
Authors: McEwen Kirsten R. , Linnett Sarah , Leitch Harry G. , Srivastava Prashant , Al-Zouabi Lara , Huang Tien-Chi , Rotival Maxime , Sardini Alessandro , Chan Thalia E. , Filippi Sarah , Stumpf Michael P.H. , Petretto Enrico , Hajkova Petra
Published: July 2018

Pluripotent stem cells (PSCs) can self-renew indefinitely while maintaining the ability to generate all cell types of the body. This plasticity is proposed to require heterogeneity in gene expression, driving a metastable state which may allow flexible cell fate choices. Contrary to this, naive PSC grown in fully defined ‘2i’ environmental conditions, containing small molecule inhibitors of MEK and GSK3 kinases, show homogenous pluripotency and lineage marker expression. However, here we show that 2i induces greater genome-wide heterogeneity than traditional serum-containing growth environments at the population level across both male and female PSCs. This heterogeneity is dynamic and reversible over time, consistent with a dynamic metastable equilibrium of the pluripotent state. We further show that the 2i environment causes increased heterogeneity in the calcium signalling pathway at both the population and single-cell level. Mechanistically, we identify loss of robustness regulators in the form of negative feedback to the upstream EGF receptor. Our findings advance the current understanding of the plastic nature of the pluripotent state and highlight the role of signalling pathways in the control of transcriptional heterogeneity. Furthermore, our results have critical implications for the current use of kinase inhibitors in the clinic, where inducing heterogeneity may increase the risk of cancer metastasis and drug resistance.
Modelling predation and mortality rates from the fossil record of gastropods
Authors: Budd Graham E. , Mann Richard P.
Published: July 2018

Gastropods often show signs of unsuccessful attacks by predators in the form of healed scars in their shells. As such, fossil gastropods can be taken as providing a record of predation through ge-ological time. However, interpreting the number of such scars has proved to be problematic - would a low number of scars mean a low rate of attack, or a high rate of success, for example? Here we develop a model of scar formation, and formally show that in general these two variables cannot be disambiguated without further information about population structure. Nevertheless, by making the probably reasonable assumptions that the non-predatory death rate is both constant and low, we show that it is possible to use relatively small assemblages of gastropods to produce accurate estimates of both attack and success rates, if the overall death rate can be estimated. We show in addition what sort of information would be required to solve this problem in more general cases. However, it is unlikely that it will be possible to extract the relevant information easily from the fossil record: a variety of important collection and taphonomic biases are likely to intervene to obscure the data that gastropod assemblages may yield.
De Novoassembly of the goldfish (Carassius auratus) genome and the evolution of genes after whole genome duplication
Authors: Chen Zelin , Omori Yoshihiro , Koren Sergey , Shirokiya Takuya , Kuroda Takuo , Miyamoto Atsushi , Wada Hironori , Fujiyama Asao , Toyoda Atsushi , Zhang Suiyuan , Wolfsberg Tyra G. , Kawakami Koichi , Phillippy Adam M. ,   NISC Comparative Sequencing Program, Mullikin James C. , Burgess Shawn M.
Published: July 2018

For over a thousand years throughout Asia, the common goldfish (Carassius auratus) was raised for both food and as an ornamental pet. Selective breeding over more than 500 years has created a wide array of body and pigmentation variation particularly valued by ornamental fish enthusiasts. As a very close relative of the common carp (Cyprinus carpio), goldfish shares the recent genome duplication that occurred approximately 14-16 million years ago (mya) in their common ancestor. The combination of centuries of breeding and a wide array of interesting body morphologies is an exciting opportunity to link genotype to phenotype as well as understanding the dynamics of genome evolution and speciation. Here we generated a high-quality draft sequence of a “Wakin” goldfish using 71X PacBio long-reads. We identified 70,324 coding genes and more than 11,000 non-coding transcripts. We found that the two sub-genomes in goldfish retained extensive synteny and collinearity between goldfish and zebrafish. However, “ohnologous” genes were lost quickly after the carp whole-genome duplication, and the expression of 30% of the retained duplicated gene diverged significantly across seven tissues sampled. Loss of sequence identity and/or exons determined the divergence of the expression across all tissues, while loss of conserved, non-coding elements determined expression variance between different tissues. This draft assembly also provides an important resource for comparative genomics with the very commonly used zebrafish model (Danio rerio), and for understanding the underlying genetic causes of goldfish variants.
Subjective perceptual experience tracks the neural signature of sensory evidence accumulation during decision formation
Authors: Tagliabue Chiara F. , Veniero Domenica , Benwell Christopher S. Y. , Cecere Roberto , Savazzi Silvia , Thut Gregor
Published: July 2018

How neural representations of low-level visual information are accessed by higher-order processes to inform decisions and give rise to conscious experience is a longstanding question. Research on perceptual decision making has revealed a late event-related EEG potential (the Centro-Parietal Positivity, CPP) to be a correlate of the accumulation of sensory evidence. We tested to what extent this evidence accumulation signal is driven by externally presented (physical) versus internally experienced (subjective) sensory evidence. The results show that the known relationship between external evidence and the evidence accumulation signal (reflected in the CPP amplitude) is mediated by the level of subjective awareness. Additionally, the CPP closely tracks the subjective perceptual evidence during both correct and incorrect trials. Hence, a remarkably close relationship exists between the evidence accumulation process (i.e. CPP) and subjective perceptual experience, suggesting that neural decision processes and components of conscious experience are tightly linked.
Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion
Authors: Khattar Vinayak , Lee Joo Hyoung , Wang Hong , Bastola Soniya , Ponnazhagan Selvarangan
Published: July 2018

The short half-life and use of recombinant bone morphogentic protein (BMP)-2 in large doses poses major limitations in the clinic. Events regulating post-translational processing and degradation of BMP2 in situ, linked to its secretion, have not been understood. Towards identifying mechanisms regulating intracellular BMP2 stability, we first discovered that inhibiting proteasomal degradation enhances both intracellular BMP2 level and its extracellular secretion. Next, we identified BMP2 degradation occurs through an ubiquitin-mediated mechanism. Since ubiquitination precedes proteasomal turnover and mainly occurs on lysine residues of nascent proteins, we systematically mutated individual lysine residues within BMP2 and tested them for enhanced stability. Results revealed that substitutions on four lysine residues within the pro-BMP2 region and three in the mature region increased both BMP2 turnover and extracellular secretion. Structural modeling revealed key lysine residues involved in proteasomal degradation occupy a lysine cluster near proprotein convertase cleavage site. Interestingly, mutations within these residues did not affect biological activity of BMP2. These data suggest preventing intracellular proteasomal loss of BMP2 through genetic modifications can overcome limitations related to its short half-life.
EphB2 and ERK signaling are required for heterotypic contact inhibition of locomotion to drive cell sorting
Authors: Brayford Simon , Serna-Morales Eduardo , Luchici Andrei , Hiratsuka Toru , Stramer Brian M.
Published: July 2018

Interactions between different cell-types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesized to control population-wide behaviors during embryogenesis [1, 2]. However, our understanding of the signals that lead to cell-type specific repulsion, and the precise capacity of heterotypic CIL responses to drive emergent behaviors is lacking. Using a new in vitro model of heterotypic CIL between epithelial and mesenchymal cells, we show that fibrosarcoma cells (HT1080), but not fibroblasts (NIH3T3), are actively repelled by epithelial cells in culture. We show that knocking down EphB2 in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. Furthermore, this heterotypic interaction requires ERK activation, downstream of EphB2 signaling. We also examine the population-wide effects when these various cell combinations, and their specific heterotypic CIL responses, are allowed to interact in culture. Mixtures of fibrosarcoma and epithelial cells – unlike fibroblasts and epithelial cells – lead to complete sorting and segregation of the two populations, and inhibiting their distinct CIL response by knocking down EphB2 or ERK in fibrosarcoma cells disrupts this emergent sorting behavior. Our understanding of the mechanisms underlying developmental behaviors such as cell sorting is lacking as predominant sorting hypotheses, such as differential adhesion, have recently been found inadequate in predicting the sorting of mesenchymal cells [3, 4]. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations during embryogenesis.
Unidirectional monosynaptic connections from auditory areas to the primary visual cortex in the marmoset monkey
Authors: Majka Piotr , Rosa Marcello G. P. , Bai Shi , Chan Jonathan M. , Huo Bing-Xing , Jermakow Natalia , Lin Meng K. , Takahashi Yeonsook S. , Wolkowicz Ianina H. , Worthy Katrina H. , Rajan Ramesh , Reser David H. , Wójcik Daniel K. , Okano Hideyuki , Mitra Partha P.
Published: July 2018

Until the late 20th Century, it was believed that different sensory modalities were processed by largely independent pathways in the primate cortex, with cross-modal integration only occurring in specialized polysensory areas. This model was challenged by the finding that the peripheral representation of the primary visual cortex (V1) receives monosynaptic connections from areas of the auditory cortex in the macaque. However, auditory projections to V1 have not been reported in other primates. We investigated the existence of direct interconnections between V1 and auditory areas in the marmoset, a New World monkey. Labelled neurons in auditory cortex were observed following 4 out of 10 retrograde tracer injections involving V1. These projections to V1 originated in the caudal subdivisions of auditory cortex (primary auditory cortex, caudal belt and parabelt areas), and targeted parts of V1 that represent parafoveal and peripheral vision. Injections near the representation of the vertical meridian of the visual field labelled few or no cells in auditory cortex. We also placed 8 retrograde tracer injections involving core, belt and parabelt auditory areas, none of which revealed direct projections from V1. These results confirm the existence of a direct, nonreciprocal projection from auditory areas to V1 in a different primate species, which has evolved separately from the macaque for over 30 million years. The essential similarity of these observations between marmoset and macaque indicate that early-stage audiovisual integration is a shared characteristic of primate sensory processing.
Structural analysis of 2-iodobenzamide and 2-iodo-N-phenylbenzamide
Authors: Bairagi Keshab M. , Kumar Vipin B. S. , Bhandary Subhrajyoti , Venugopala Katharigatta N. , Nayak Susanta K.
Published: July 2018

The title compounds, 2-iodobenzamide, C7H6INO (I), and 2-iodo-N-phenylbenzamide, C13H10INO (II), were both synthesized from 2-iodobenzoic acid. In the crystal structure of (I), N—H...O and hydrogen bonds form two sets of closed rings, generating dimers and tetramers. These combine with C—I...π(ring) halogen bonds to form sheets of molecules in the bc plane. For (II), N—H...O hydrogen bonds form chains along the a-axis direction, while inversion-related C—I...π(ring) contacts supported by C—H...π(ring) interactions generate sheets of molecules along the ab diagonal.
One‐year mortality among newly admitted older patients in a long‐term care hospital in South Korea
Authors: Kim Mi Sook , Shin Dong‐Soo , Kim SookNyeo
Published: July 2018

Objectives

Older Korean people's admission to long‐term care (LTC) hospitals is increasing. This study aimed to investigate one‐year mortality and related factors among older patients admitted to a LTC hospital.

Methods

Medical records of 330 patients admitted to a LTC hospital in 2014 were reviewed. Factors related to death were identified using the Cox proportional hazards model.

Results

About 35% of the patients died within a year, and their average length of survival was 42.3 (SD = 68.4) days. Predictors of mortality within one year were as follows: cancer (hazard ratio (HR) = 3.04); aged 85 and older (HR = 2.61); dependency: K‐ADL ≥ 21 (HR = 2.14); male sex (HR = 1.95); respiratory disease (HR = 1.68); cognitive function (HR = 1.65); and abnormal serum sodium level (HR = 1.65).

Conclusion

At admission, proper assessment and planning for older patients at risk are beneficial to minimise negative consequences. The roles of LTC hospitals need further discussion.
Physical Activity, Well‐Being, and the Basic Psychological Needs: Adopting the SDT Model of Eudaimonia in a Post‐Cardiac Rehabilitation Sample
Authors: Saunders Chelsey , Huta Veronika , Sweet Shane N.
Published: July 2018

Background

The theoretical conceptualisation of hedonic (HWB; pleasure) and eudaimonic (EWB; meaning) well‐being has rarely been examined among cardiac rehabilitation (CR) graduates, including its relationship with moderate‐to‐vigorous physical activity (MVPA). First, this study examined the potential bidirectional relationship between MVPA and HWB/EWB. Second, this study tested the self‐determination theory (SDT) model of eudaimonia where MVPA was set to predict the model's pathway between eudaimonic motives (seeking meaning), the basic psychological needs (autonomy, competence, and relatedness), and both types of well‐being.

Methods

Individuals who completed a CR program within the last five years (N = 57) answered well‐being and basic psychological needs questionnaires and wore an accelerometer to measure MVPA at baseline and three months later.

Results

MVPA predicted changes in both HWB (β = .13) and EWB (β = .13) three months later. Only the EWB–MVPA relationship (β = .16) approached significance, hinting at a bidirectional relationship. The SDT model of eudaimonia was supported and MVPA had a moderate to small relationship with eudaimonic motives.

Conclusion

This study showed a potential bidirectional relationship between MVPA and EWB and tested the SDT model of eudaimonia with MVPA in post‐cardiac rehabilitation. Future interventions could look to simultaneously promote eudaimonia and MVPA among this population.
Civil society organizations and participatory local governance in Pakistan: An exploratory study
Authors: Rosilawati Yeni , Rafique Zain , Nikku Bala Raju , Habib Shahid
Published: July 2018

This paper analyses the extent to which the civil society organizations (CSOs) have influenced the decision‐making of the local government toward the needs and priorities of citizens. In development discourse, civil society organizations hold a significant importance as they are deemed to provide holistic and new ways to ensure participatory local governance. Therefore, their role against the backdrop of their involvement in mobilizing citizens’ involvement and influencing decision‐making in Pakistan calls for further research. This paper aims to fill this gap. Using qualitative research methods, the current paper appraises the role of CSOs in mobilizing public involvement in the decision‐making process of local government institutions of Punjab, Pakistan. The paper finds that the effectiveness of CSOs is very low due to various institutional and political constraints. Motivations for CSOs seeking citizen involvement have been instrumental in nature rather than motivated by participatory principles.
Uterus transplantation as radical reproduction: Taking the adoption alternative more seriously
Authors: Lotz Mianna
Published: July 2018

This paper urges reconsideration of analyses of the alternatives to reproductive uterus transplantation (UTx). I focus here specifically on the adoption alternative. Importantly, my purpose is not to oppose UTx provision. Rather, it is to propose ways in which ethical analysis and provision of UTx can potentially accommodate the concerns discussed here. I argue that the adoption alternative to UTx is too readily dismissed, and that this is a dismissal with significant moral costs. I suggest that the radical nature of UTx as a form of assisted reproduction calls for an equivalently radical socio‐moral agenda for reform and transformation of adoption law, policy and practice, as well as of the norms that prevail within our presently strongly bio‐normative reproductive context. In doing so I widen the ethical frame of responsible provision of assisted reproduction to encompass not just obligations towards donors and recipient, but also our broader social responsibilities to ensure that we are doing our best to meet the significant needs of some of the most vulnerable members of our society.
Genetic and clinical characterization of B7‐H3 (CD276) expression and epigenetic regulation in diffuse brain glioma
Authors: Wang Zhiliang , Wang Zheng , Zhang Chuanbao , Liu Xing , Li Guanzhang , Liu Shuai , Sun Lihua , Liang Jingshan , Hu Huimin , Liu Yanwei , Zhang Wei , Jiang Tao
Published: July 2018

Gliomas are the most common malignant tumors of the brain. Immune checkpoints have been increasingly emphasized as targets for treating malignant tumors. B7‐H3 has been identified as an immune checkpoint that shows potential value for targeting therapies. We set out to characterize the expression pattern and biological function of B7‐H3 in brain gliomas using high‐throughput data obtained from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) projects. B7‐H3 was upregulated more in higher‐grade gliomas than that in lower‐grade gliomas in both CGGA and TCGA datasets. Isocitrate dehydrogenase (IDH) mutation seemed to exert significant influence on B7‐H3 expression in gliomas but led to quite different results between grade II gliomas and higher‐grade gliomas. In addition to IDH, methylation of B7‐H3 promoter and microRNA‐29 family also showed a potential regulatory effect on B7‐H3 expression. Gene ontology analysis revealed that B7‐H3 was associated with mitotic cell cycle, cell proliferation and immune response. Further investigation suggested that B7‐H3 was mostly involved in the Toll‐like receptor signaling pathway. Survival analysis indicated that B7‐H3 was an independent unfavorable prognosticator for glioma patients in both CGGA and TCGA datasets. B7‐H3 expression is regulated by multiple mechanisms and is potentially involved in the T‐cell receptor signaling pathway. Higher B7‐H3 expression indicates a worse prognosis for glioma patients, which warrants further research into the development of inhibitors for targeting this immune checkpoint, but we still need to be cautious about immune checkpoint inhibition for central nervous system tumors.
Like parent, like child? Exploring the association between early maladaptive schemas of adolescents involved with Child Protective Services and their parents
Authors: Zonnevijlle Marian , Hildebrand Martin
Published: July 2018

Although early maladaptive schemas (EMS) have been successfully identified in a variety of adult samples and increasing evidence suggests that core maladaptive schemas can also be retrieved in children and adolescents, there is a dearth of research examining the association between maladaptive schemas of parents and their children. We designed the current exploratory study as a first step to investigate similarities and differences in EMS of adolescents (n = 20) involved with Child Protective Services and their parents (n = 20). Results demonstrated that there were some similarities in the specific EMS endorsed by both groups and that most of the significant correlations that were found between parents' and youths' EMS involved parent schemas of the Impaired limits and Disconnection/rejection domains and youths' schemas of the Disconnection/rejection and Impaired autonomy and performance domains. We also found significant positive correlations between several children's EMS and perceived parental rearing styles (i.e., rejection, control/overprotection, anxious rearing) and attachment anxiety.
Acquisition and Validation of Spectral Ground Truth Data for Predictive Rendering of Rough Surfaces
Authors: Clausen O. , Marroquim R. , Fuhrmann A.
Published: July 2018

Physically based rendering uses principles of physics to model the interaction of light with matter. Even though it is possible to achieve photorealistic renderings, it often fails to be predictive. There are two major issues: first, there is no analytic material model that considers all appearance critical characteristics; second, light is in many cases described by only 3 RGB‐samples. This leads to the problem that there are different models for different material types and that wavelength dependent phenomena are only approximated. In order to be able to analyze the influence of both problems on the appearance of real world materials, an accurate comparison between rendering and reality is necessary. Therefore, in this work, we acquired a set of precisely and spectrally resolved ground truth data. It consists of the precise description of a new developed reference scene including isotropic BRDFs of 24 color patches, as well as the reference measurements of all patches under 13 different angles inside the reference scene. Our reference data covers rough materials with many different spectral distributions and various illumination situations, from direct light to indirect light dominated situations.
Deep Painterly Harmonization
Authors: Luan Fujun , Paris Sylvain , Shechtman Eli , Bala Kavita
Published: July 2018

Copying an element from a photo and pasting it into a painting is a challenging task. Applying photo compositing techniques in this context yields subpar results that look like a collage — and existing painterly stylization algorithms, which are global, perform poorly when applied locally. We address these issues with a dedicated algorithm that carefully determines the local statistics to be transferred. We ensure both spatial and inter‐scale statistical consistency and demonstrate that both aspects are key to generating quality results. To cope with the diversity of abstraction levels and types of paintings, we introduce a technique to adjust the parameters of the transfer depending on the painting. We show that our algorithm produces significantly better results than photo compositing or global stylization techniques and that it enables creative painterly edits that would be otherwise difficult to achieve.
Efficient Caustic Rendering with Lightweight Photon Mapping
Authors: Grittmann Pascal , Pérard‐Gayot Arsène , Slusallek Philipp , Křivánek Jaroslav
Published: July 2018

Robust and efficient rendering of complex lighting effects, such as caustics, remains a challenging task. While algorithms like vertex connection and merging can render such effects robustly, their significant overhead over a simple path tracer is not always justified and – as we show in this paper ‐ also not necessary. In current rendering solutions, caustics often require the user to enable a specialized algorithm, usually a photon mapper, and hand‐tune its parameters. But even with carefully chosen parameters, photon mapping may still trace many photons that the path tracer could sample well enough, or, even worse, that are not visible at all.

Our goal is robust, yet lightweight, caustics rendering. To that end, we propose a technique to identify and focus computation on the photon paths that offer significant variance reduction over samples from a path tracer. We apply this technique in a rendering solution combining path tracing and photon mapping. The photon emission is automatically guided towards regions where the photons are useful, i.e., provide substantial variance reduction for the currently rendered image. Our method achieves better photon densities with fewer light paths (and thus photons) than emission guiding approaches based on visual importance. In addition, we automatically determine an appropriate number of photons for a given scene, and the algorithm gracefully degenerates to pure path tracing for scenes that do not benefit from photon mapping.
Possible link between photosynthesis and leaf modulus of elasticity among vascular plants: a new player in leaf traits relationships?
Authors: Nadal Miquel , Flexas Jaume , Gulías Javier
Published: July 2018

A compromise between carbon assimilation and structure investment at the leaf level is broadly accepted, yet the relationship between net assimilation per area (An) and leaf mass per area has been elusive. We propose bulk modulus of elasticity (ε) as a suitable parameter to reflect both leaf structure and function, and an inverse relationship between ε and An and mesophyll conductance (gm) is postulated. Using data for An, gm and ε from previous studies and new measurements on a set of 20 species covering all major growth forms, a negative relationship between An or gm and ε was observed. High ε was also related to low leaf capacitance and higher diffusive limitations to photosynthesis. In conclusion, ε emerges as a key trait linked with photosynthetic capacity across vascular plants, and its relationship with gm suggests the existence of a common mechanistic basis, probably involving a key role of cell walls.
Impaired neural stem cell expansion and hypersensitivity to epileptic seizures in mice lacking the EGFR in the brain
Authors: Robson Jonathan P. , Wagner Bettina , Glitzner Elisabeth , Heppner Frank L. , Steinkellner Thomas , Khan Deeba , Petritsch Claudia , Pollak Daniela D. , Sitte Harald H. , Sibilia Maria
Published: July 2018

Mice lacking the epidermal growth factor receptor (EGFR) develop an early postnatal degeneration of the frontal cortex and olfactory bulbs and show increased cortical astrocyte apoptosis. The poor health and early lethality of EGFR−/− mice prevented the analysis of mechanisms responsible for the neurodegeneration and function of the EGFR in the adult brain. Here, we show that postnatal EGFR‐deficient neural stem cells are impaired in their self‐renewal potential and lack clonal expansion capacity in vitro. Mice lacking the EGFR in the brain (EGFRΔbrain) show low penetrance of cortical degeneration compared to EGFR−/− mice despite genetic recombination of the conditional allele. Adult EGFRΔ mice establish a proper blood–brain barrier and perform reactive astrogliosis in response to mechanical and infectious brain injury, but are more sensitive to Kainic acid‐induced epileptic seizures. EGFR‐deficient cortical astrocytes, but not midbrain astrocytes, have reduced expression of glutamate transporters Glt1 and Glast, and show reduced glutamate uptake in vitro, illustrating an excitotoxic mechanism to explain the hypersensitivity to Kainic acid and region‐specific neurodegeneration observed in EGFR‐deficient brains.