bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate Alexander colorings
Authors: Traldi Lorenzo
Published: September 2018

We extend the notion of link colorings with values in an Alexander quandle to link colorings with values in a module [Formula: see text] over the Laurent polynomial ring [Formula: see text]. If [Formula: see text] is a diagram of a link [Formula: see text] with [Formula: see text] components, then the colorings of [Formula: see text] with values in [Formula: see text] form a [Formula: see text]-module [Formula: see text]. Extending a result of Inoue [Knot quandles and infinite cyclic covering spaces, Kodai Math. J. 33 (2010) 116–122], we show that [Formula: see text] is isomorphic to the module of [Formula: see text]-linear maps from the Alexander module of [Formula: see text] to [Formula: see text]. In particular, suppose [Formula: see text] is a field and [Formula: see text] is a homomorphism of rings with unity. Then [Formula: see text] defines a [Formula: see text]-module structure on [Formula: see text], which we denote [Formula: see text]. We show that the dimension of [Formula: see text] as a vector space over [Formula: see text] is determined by the images under [Formula: see text] of the elementary ideals of [Formula: see text]. This result applies in the special case of Fox tricolorings, which correspond to [Formula: see text] and [Formula: see text]. Examples show that even in this special case, the higher Alexander polynomials do not suffice to determine [Formula: see text]; this observation corrects erroneous statements of Inoue [Quandle homomorphisms of knot quandles to Alexander quandles, J. Knot Theory Ramifications 10 (2001) 813–821; op. cit.].
EFFECT OF THE POLYACRYLAMIDE FERROGEL ELASTICITY ON THE CELL ADHESIVENESS TO MAGNETIC COMPOSITE
Authors: BLYAKHMAN F. A. , SAFRONOV A. P. , MAKEYEV O. G. , MELEKHIN V. V. , SHKLYAR T. F. , ZUBAREV A. Y. , MAKAROVA E. B. , SICHKAR D. A. , RUSINOVA M. A. , SOKOLOV S. Y. , KURLYANDSKAYA G. V.
Published: September 2018

Biocompatible polyacrylamide gels are widely required for the development of mechanically “soft” magnetic material for the purposes of different biomedical applications. In this work, ferrogels were synthesized by radical polymerization of acrylamide in a stable aqueous suspension of magnetic maghemite [Formula: see text]-Fe[Formula: see text]O[Formula: see text] nanoparticles (MNPs) with the median value in diameter of 11.4[Formula: see text]nm fabricated by laser target evaporation. Gel network density was set to 1:100, the concentrations of embedded MNPs were fixed at 0.00%, 0.25%, 0.50%, 0.75% or 1.0% by weight. Ferrogels’ Young’s modulus and affinity to the human dermal fibroblasts adhesiveness were tested. To estimate the cells adhesive activity to gels, the adhesion index was calculated as the number of adhered cells divided by the number of cells sown and multiplied by 100%. The gradual increase of MNPs concentration in the gel network resulted in the significant increase of ferrogel’s Young’s modulus and cells adhesion activity. In particular, at the MNPs concentration of 0.25%, the modulus and the adhesion index were equal to [Formula: see text]30[Formula: see text]kPa and [Formula: see text]90%, correspondingly. The adhesion index at highest MNPs concentration of 1.0% was close to 100% and modulus to [Formula: see text]40[Formula: see text]kPa. The increase of cells adhesiveness rise with MNPs concentration closely correlated with the direct impact of MNPs on the gel stiffness.
INVESTIGATION OF BONE DRILLING FOR SECURE IMPLANT FIXATION IN HUMAN FEMURS: TAGUCHI OPTIMIZATION AND PREDICTIVE FORCE MODELS WITH EXPERIMENTAL VALIDATION
Authors: PANDITHEVAN PONNUSAMY , PANDY NATARAJAN VINAYAGA MURUGA , PRASANNAVENKADESAN VARATHARAJAN
Published: September 2018

Drilling procedures are important to optimize and ensure the strongest fixation in bone fracture treatment and reconstruction surgery. The mechanistic force models currently available for bovine bones, human spines and human mandibles are not relevant to perform drilling through human femurs. The present study addresses this lack of information and aims to develop the predictive force models for drilling human femurs at different regions and directions. In this study, 10 freshly harvested cadaveric human femurs were included, and a surgical drill bit of 3.2[Formula: see text]mm diameter was used to make 4[Formula: see text]mm deep holes. Different spindle speeds (500, 1000 and 1500[Formula: see text]rpm), feed rates (40, 60 and 80[Formula: see text]mm/min), and apparent density between 0.98 and 1.98[Formula: see text]g/cm3were considered. The optimal parameters [Formula: see text], [Formula: see text], and [Formula: see text] respectively obtained for longitudinal, radial, and circumferential direction could minimize the thrust forces in bone drilling by up to 7.70, 10.50, and 16.20 N, respectively. Validation study demonstrated that the force model developed could predict the thrust force from computed tomography data sets of the patient, only with 5.05%, 6.74%, and 4.91% as a maximum error in longitudinal, radial, and circumferential direction. This important tool can assist to perform complicated surgical operations.
Phase-Locking of Spin-Torque Nano-Oscillator Pairs by Magnetic Dipolar Coupling in Electrical Serial Connection
Authors: Chen Hao-Hsuan , Zeng Lang , Zhao Weisheng , Liu Yaowen
Published: September 2018

Synchronization of spin-torque nano-oscillators (STNOs) by magnetic dipolar interactions in a parallel electrical connection (PC) introduces the technological possibility for an enhancement of output signal. In this study, we consider two identical or nonidentical STNOs in serial electrical connection (SC). By using a pendulum-like approximation model, we analytically predict the dipolar coupling strength, critical current and frequency of phase-locking precession. The numerical calculations of those analytical expressions are confirmed by macrospin simulations, revealing that the dipolar coupling strength responsible for the phase-locking in SC case is three times larger than that in the PC case for the two STNOs with the same separation, which results in the enlarged and symmetric phase-locking window of frequency versus current. These results suggest that the SC of multiple STNOs could be more promising for the enhancement of output power.
A 3D Rotating Laser-Based Navigation Solution for Micro Aerial Vehicles in Dynamic Environments
Authors: Qin Hailong , Bi Yingcai , Feng Lin , Zhang Y. F. , Chen Ben M.
Published: September 2018

In this paper, we present a 3D rotating laser-based navigation framework for micro aerial vehicles (MAVs) to fly autonomously in dynamic environments. It consists of a 6-degree of freedom (DoF) localization module and a 3D dynamic mapping module. A self-designed rotating laser scanner generates dense point clouds in which 3D features are extracted and aligned. The localization module is able to solve scan distortion issue while estimating the 6-DoF pose of MAVs. At the same time, the dynamic mapping module can further eliminate dynamic trails so that a clear dense 3D map is reconstructed. The dynamic targets are detected based on the spatial constraints and therefore without the need of dense point cloud clustering. Through filtering the detected dynamic obstacles, the localization approach can be robust to the dynamic environment variations. To verify the robustness and effectiveness of our proposed framework, we have tested our system in both real indoor environment with dynamic obstacles and outdoor foliage condition using a customized MAV platform.
Crime and the Life-Course, Prevention, Experiments, and Truth Seeking: Joan McCord's Pioneering Contributions to Criminology
Authors: Tremblay Richard E. , Welsh Brandon C. , Sayre-McCord Geoffrey
Published: September 2018

A life-span developmental approach describes Joan McCord's career and highlights her pioneering contributions to criminology and, more broadly, to understanding human development. The main focus of this article is on her exceptional scientific contributions through the assessment of the Cambridge-Somerville Youth Study experimental preventive intervention. We highlight her efforts to understand how a delinquency prevention intervention caused iatrogenic effects and the lessons she drew for evaluation research. Important contributions to key issues in developmental criminology are summarized, such as the different roles of mothers, fathers, and neighborhoods in the development of delinquency as well as the importance of differentiating discipline from punishment. We describe how Dr. McCord relied on philosophy, how she tackled oppositions between theory-driven and data-driven research in criminology, and how she helped young investigators learn how to learn, and we end by highlighting her contributions to the organization and development of criminology in the United States and around the world.
The Real Gold Standard: Measuring Counterfactual Worlds That Matter Most to Social Science and Policy
Authors: Nagin Daniel S. , Sampson Robert J.
Published: September 2018

The randomized experiment has achieved the status of the gold standard for estimating causal effects in criminology and the other social sciences. Although causal identification is indeed important and observational data present numerous challenges to causal inference, we argue that conflating causality with the method used to identify it leads to a cognitive narrowing that diverts attention from what ultimately matters most—the difference between counterfactual worlds that emerge as a consequence of their being subjected to different treatment regimes applied to all eligible population members over a sustained period of time. To address this system-level and long-term challenge, we develop an analytic framework for integrating causality and policy inference that accepts the mandate of causal rigor but is conceptually rather than methodologically driven. We then apply our framework to two substantive areas that have generated high-visibility experimental research and that have considerable policy influence: ( a) hot-spots policing and ( b) the use of housing vouchers to reduce concentrated disadvantage and thereby crime. After reviewing the research in these two areas in light of our framework, we propose a research path forward and conclude with implications for the interplay of theory, data, and causal understanding in criminology and other social sciences.
Systemic Risk 10 Years Later
Authors: Engle Robert
Published: September 2018

Ten years ago, the financial crisis spurred research focused on systemic risk. This article examines the history and application of the SRISK measure, which was developed at that time and is now widely used in monitoring systemic risk around the globe. The concept is explained and a variety of ways to measure SRISK are developed. In this article, new results are presented on the uncertainty associated with the SRISK measure and on how it compares with other related measures from both academics and regulators. By focusing on the mechanism by which undercapitalization of the financial sector initiates a financial crisis, new research examines how the probability of a financial crisis is affected by the level of SRISK and, consequently, how much SRISK a country can stand without having a high probability of crisis. The model used to evaluate this probability recognizes the externalities between financial institutions that make an undercapitalized firm or country more fragile if other firms and countries are also undercapitalized.
Personality and Coping: Individual Differences in Responses to Emotion
Authors: Segerstrom Suzanne C. , Smith Gregory T.
Published: September 2018

Abundant evidence links personality with emotion via coping. Alternatively, personality can be viewed as an emergent property of responses to the experience of emotion. Dispositions to control, approach, escape, and avoid one's emotional experience underlie diverse traits, including positive and negative urgency, trait emotional approach and avoidance, alexithymia, and emotional expressiveness. In this review, we consider the neurobiological underpinnings of these dispositions and the nature (e.g., stability) and adaptiveness of the associated traits. Important future directions for research in this area include the roles of development, intraindividual variability and flexibility, and the intensity and structure of emotional experience.
Western diet triggers Toll-like receptor 4 signaling-induced endothelial dysfunction in female Wistar rats
Authors: Kramer Benjamin , França Lucas Martins , Zhang Youhua , Paes Antonio Marcus de Andrade , Gerdes A. Martin , Carrillo-Sepulveda Maria Alicia
Published: September 2018

Overconsumption of a diet rich in fat and carbohydrates, called the Western diet, is a major contributor to the global epidemic of cardiovascular disease. Despite previously documented cardiovascular protection exhibited in female rats, this safeguard may be lost under certain metabolic stressors. We hypothesized that female Wistar rats challenged by a Western diet composed of 21% fat and 50% carbohydrate (34.1% sucrose) for 17 wk would develop endothelial dysfunction via endothelial Toll-like receptor 4 (TLR4) signaling. Western diet-fed female rats exhibited dysregulation of metabolism, revealing increased body weight and abdominal fat, decreased expression of adiponectin in white adipose tissue, glucose intolerance, and impaired insulin sensitivity. Western diet exposure increased hepatic triglycerides and cholesterol alongside hepatic steatosis, categorizing nonalcoholic fatty liver disease. Moreover, a Western diet negatively affected vascular function, revealing hypertension, impaired endothelium-dependent vasorelaxation, aortic remodeling, and increased reactive oxygen species (ROS) production. Aortic protein expression of TLR4 and its downstream proteins were markedly increased in the Western diet-fed group in association with elevated serum levels of free fatty acids. In vitro experiments were conducted to test whether free fatty acids contribute to vascular ROS overproduction via the TLR4 signaling pathway. Cultured endothelial cells were stimulated with palmitate in the presence of TAK-242, a TLR4 signaling inhibitor. Palmitate-induced overgeneration of ROS in endothelial cells was abolished in the presence of TAK-242. Our data show that a Western diet induced endothelial dysfunction in female rats and suggest that endothelial TLR4 signaling may play a key role in abolishing female cardiovascular protection.

NEW & NOTEWORTHY A Western diet induced elevated levels of free fatty acids, produced nonalcoholic fatty liver disease, and provoked endothelial dysfunction in female rats in association with Toll-like receptor 4 signaling-mediated vascular reactive oxygen species production. Limited consumption of a Western diet in premenopausal women may decrease their risk of cardiovascular complications.
Altered biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and right ventricular volume overload because of pulmonary regurgitation
Authors: Sjöberg Pia , Töger Johannes , Hedström Erik , Arvidsson Per , Heiberg Einar , Arheden Håkan , Gustafsson Ronny , Nozohoor Shahab , Carlsson Marcus
Published: September 2018

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery.

NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.
Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats
Authors: Huc Tomasz , Drapala Adrian , Gawrys Marta , Konop Marek , Bielinska Klaudia , Zaorska Ewelina , Samborowska Emilia , Wyczalkowska-Tomasik Aleksandra , Pączek Leszek , Dadlez Michal , Ufnal Marcin
Published: September 2018

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHR-TMAO group had lower plasma NH2-terminal pro-B-type natriuretic peptide, LVEDP, and cardiac fibrosis. In contrast to age-matched WKY rats, 60-wk-old SHRs showed hypertensive angiopathy and heart failure with preserved ejection fraction. Compared with the SHR-Water group, the SHR-TMAO group (56-wk TMAO treatment) showed significantly lower plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, significantly lower LVEDP, and cardiac fibrosis. In conclusion, a four- to fivefold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in pressure-overloaded hearts in rats.

NEW & NOTEWORTHY Chronic, low-dose trimethylamine oxide (TMAO) treatment that increases plasma TMAO by four- to fivefold reduces plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, left ventricular end-diastolic pressure, and cardiac fibrosis in pressure-overloaded hearts in hypertensive rats. Our study provides evidence that a moderate increase in plasma TMAO does not have a negative effect on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in the pressure-overloaded heart.
Identification of loci affecting sexually dimorphic patterns for height and recurrent laryngeal neuropathy risk in American Belgian Draft Horses
Authors: Brooks Samantha A. , Stick John , Braman Ashley , Palermo Katelyn , Robinson N. Edward , Ainsworth Dorothy M.
Published: September 2018

Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown etiology. In Thoroughbreds (TB), we previously demonstrated that the haplotype association for height (LCORL/NCAPG locus on ECA3, which affects body size) and RLN was coincident. In the present study, we performed a genome-wide association scan (GWAS) for RLN in 458 American Belgian Draft Horses, a breed fixed for the LCORL/NCAPG risk alelle. In this breed, RLN risk is associated with sexually dimorphic differences in height, and we identified a novel locus contributing to height in a sex-specific manner: MYPN (ECA1). Yet this specific locus contributes little to RLN risk, suggesting that other growth traits correlated to height may underlie the correlation to this disease. Controlling for height, we identified a locus on ECA15 contributing to RLN risk specifically in males. These results suggest that loci with sex-specific gene expression play an important role in altering growth traits impacting RLN etiology, but not necessarily adult height. These newly identified genes are promising targets for novel preventative and treatment strategies.
Targeting Lineage-specific MITF Pathway in Human Melanoma Cell Lines by A-485, the Selective Small-molecule Inhibitor of p300/CBP
Authors: Wang Rui , He Yupeng , Robinson Valerie , Yang Ziping , Hessler Paul , Lasko Loren M. , Lu Xin , Bhathena Anahita , Lai Albert , Uziel Tamar , Lam Lloyd T.
Published: September 2018

Metastatic melanoma is responsible for approximately 80% of deaths from skin cancer. Microphthalmia-associated transcription factor (MITF) is a melanocyte-specific transcription factor that plays an important role in the differentiation, proliferation, and survival of melanocytes as well as in melanoma oncogenesis. MITF is amplified in approximately 15% of patients with metastatic melanoma. However, no small-molecule inhibitors of MITF currently exist. MITF was shown to associate with p300/CBP, members of the KAT3 family of histone acetyltransferase. p300 and CREB-binding protein (p300/CBP) regulate a wide range of cellular events such as senescence, apoptosis, cell cycle, DNA damage response, and cellular differentiation. p300/CBP act as transcriptional coactivators for multiple proteins in cancers, including oncogenic transcription factors such as MITF. In this study, we showed that our novel p300/CBP catalytic inhibitor, A-485, induces senescence in multiple melanoma cell lines, similar to silencing expression of EP300 (encodes p300) or MITF. We did not observe apoptosis and increase invasiveness upon A-485 treatment. A-485 regulates the expression of MITF and its downstream signature genes in melanoma cell lines undergoing senescence. In addition, expression and copy number of MITF is significantly higher in melanoma cell lines that undergo A-485–induced senescence than resistant cell lines. Finally, we showed that A-485 inhibits histone-H3 acetylation but did not displace p300 at promoters of MITF and its putative downstream genes. Taken together, we provide evidence that p300/CBP inhibition suppressed the melanoma-driven transcription factor, MITF, and could be further exploited as a potential therapy for treating melanoma.
c-MYC Drives Breast Cancer Metastasis to the Brain, but Promotes Synthetic Lethality with TRAIL
Authors: Lee Ho Yeon , Cha Junghwa , Kim Seon Kyu , Park Jun Hyung , Song Ki Hoon , Kim Pilnam , Kim Mi-Young
Published: September 2018

Brain metastasis in breast cancer is particularly deadly, but effective treatments remain out of reach due to insufficient information about the mechanisms underlying brain metastasis and the potential vulnerabilities of brain-metastatic breast cancer cells. Here, human breast cancer cells and their brain-metastatic derivatives (BrMs) were used to investigate synthetic lethal interactions in BrMs. First, it was demonstrated that c-MYC activity is increased in BrMs and is required for their brain-metastatic ability in a mouse xenograft model. Specifically, c-MYC enhanced brain metastasis by facilitating the following processes within the brain microenvironment: (i) invasive growth of BrMs, (ii) macrophage infiltration, and (iii) GAP junction formation between BrMs and astrocytes by upregulating connexin 43 (GJA1/Cx43). Furthermore, RNA-sequencing (RNA-seq) analysis uncovered a set of c-MYC–regulated genes whose expression is associated with higher risk for brain metastasis in breast cancer patients. Paradoxically, however, increased c-MYC activity in BrMs rendered them more susceptible to TRAIL (TNF-related apoptosis-inducing ligand)–induced apoptosis. In summary, these data not only reveal the brain metastasis-promoting role of c-MYC and a subsequent synthetic lethality with TRAIL, but also delineate the underlying mechanism. This suggests TRAIL-based approaches as potential therapeutic options for brain-metastatic breast cancer.

Implications:

This study discovers a paradoxical role of c-MYC in promoting metastasis to the brain and in rendering brain-metastatic cells more susceptible to TRAIL, which suggests the existence of an Achilles' heel, thus providing a new therapeutic opportunity for breast cancer patients.
Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation
Authors: Gachet Stéphanie , El-Chaar Tiama , Avran David , Genesca Eulalia , Catez Frédéric , Quentin Samuel , Delord Marc , Thérizols Gabriel , Briot Delphine , Meunier Godelieve , Hernandez Lucie , Pla Marika , Smits Willem K. , Buijs-Gladdines Jessica G. , Van Loocke Wouter , Menschaert Gerben , André-Schmutz Isabelle , Taghon Tom , Van Vlierberghe Pieter , Meijerink Jules P. , Baruchel André , Dombret Hervé , Clappier Emmanuelle , Diaz Jean-Jacques , Gazin Claude , de Thé Hugues , Sigaux François , Soulier Jean
Published: September 2018

Deletion of chromosome 6q is a well-recognized abnormality found in poor-prognosis T-cell acute lymphoblastic leukemia (T-ALL). Using integrated genomic approaches, we identified two candidate haploinsufficient genes contiguous at 6q14, SYNCRIP (encoding hnRNP-Q) and SNHG5 (that hosts snoRNAs), both involved in regulating RNA maturation and translation. Combined silencing of both genes, but not of either gene alone, accelerated leukemogeneis in a Tal1/Lmo1/Notch1-driven mouse model, demonstrating the tumor-suppressive nature of the two-gene region. Proteomic and translational profiling of cells in which we engineered a short 6q deletion by CRISPR/Cas9 genome editing indicated decreased ribosome and mitochondrial activities, suggesting that the resulting metabolic changes may regulate tumor progression. Indeed, xenograft experiments showed an increased leukemia-initiating cell activity of primary human leukemic cells upon coextinction of SYNCRIP and SNHG5. Our findings not only elucidate the nature of 6q deletion but also highlight the role of ribosomes and mitochondria in T-ALL tumor progression.

Significance:

The oncogenic role of 6q deletion in T-ALL has remained elusive since this chromosomal abnormality was first identified more than 40 years ago. We combined genomic analysis and functional models to show that the codeletion of two contiguous genes at 6q14 enhances malignancy through deregulation of a ribosome–mitochondria axis, suggesting the potential for therapeutic intervention.

This article is highlighted in the In This Issue feature, p. 1494
Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors
Authors: Nirmal Ajit J. , Regan Tim , Shih Barbara B. , Hume David A. , Sims Andrew H. , Freeman Tom C.
Published: September 2018

The immune composition of the tumor microenvironment regulates processes including angiogenesis, metastasis, and the response to drugs or immunotherapy. To facilitate the characterization of the immune component of tumors from transcriptomics data, a number of immune cell transcriptome signatures have been reported that are made up of lists of marker genes indicative of the presence a given immune cell population. The majority of these gene signatures have been defined through analysis of isolated blood cells. However, blood cells do not reflect the differentiation or activation state of similar cells within tissues, including tumors, and consequently markers derived from blood cells do not necessarily transfer well to tissues. To address this issue, we generated a set of immune gene signatures derived directly from tissue transcriptomics data using a network-based deconvolution approach. We define markers for seven immune cell types, collectively named ImSig, and demonstrate how these markers can be used for the quantitative estimation of the immune cell content of tumor and nontumor tissue samples. The utility of ImSig is demonstrated through the stratification of melanoma patients into subgroups of prognostic significance and the identification of immune cells with the use of single-cell RNA-sequencing data derived from tumors. Use of ImSig is facilitated by an R package (imsig). Cancer Immunol Res; 6(11); 1388–400. ©2018 AACR.
A Rare Case of Congenital Orbital Cystic Neuroblastoma in an Infant
Authors: Kasaee Abolfazl , Rafizadeh Seyed Mohsen , Ghadimi Hadi , Shahraki Kianoosh , Asadi Amoli Fahimeh , Jamshidian-Tehrani Mansooreh
Published: September 2018

Neuroblastoma, a relatively common tumor in infants, is rarely present at birth. A solid mass is the typical appearance of this neoplasm, while cystic formation is uncommon. Congenital cystic neuroblastoma is extremely rare and no previous report exists of its occurrence in the orbit. A newborn girl was referred with an extremely large mass on the right side of her face on the third day of her life. Prenatal ultrasonography had revealed a large mass (80 × 80 mm) in the frontal area. MRI revealed a heterogeneous mass composed of cystic and solid, contrast-enhancing components. Excisional biopsy was successfully performed and histopathologic diagnosis of neuroblastoma was confirmed. Systemic workup was negative for involvement of other organs and levels of catecholamine metabolites of serum and urine (homovanillic acid and vanillylmandelic acid) were normal. Postoperative course was uneventful with complete healing of the anophthalmic socket and normal physical and mental growth and development of the infant. To our knowledge, this is the first report of congenital cystic neuroblastoma primarily arising in the orbit.
Ureter Complications: A Rare Complication but which Requires the Highest Degree of Management Expertise
Authors: Weigand Karl , Kawan Felix , Schaarschmidt Tom , Fornara Paolo
Published: September 2018

Introduction: 0% of all urinary tract injuries are iatrogenic lesions. Although they only occur in < 5%, they can lead to severe ipsilateral renal dysfunctions. These lesions can be treated with extensive knowledge on the genesis of the lesion, the anatomy, the individual patient’s history and high operative expertise in diverse surgical methods. Material and Methods: In this article, we show which reconstruction options are possible, depending on the lesion’s severity according to the AAST and EAU Guidelines from 2009 on the classification of ureter injuries, as well as the localisation. A special focus is on the anatomy. It is important to adhere to surgical ground principles, such as making sure all pathological tissue is removed, the ureter ends are spatulated and a tension-free and watertight anastomosis is maintained. Results: Iatrogenic ureter lesions are rare complications, but being able to deal with these frequently requires a urologist’s expertise. Whenever surgeons operate close to the ureters, there is always a risk of an iatrogenic ureter lesion, which in turn requires that all available reconstructive measures are used dynamically. Conclusion: Ureter complications are rare but require surgeons’ excellent management expertise.
Fistula Recurrence: A Clinical Reality after Successful Endoscopic Closure of Laparoscopic Sleeve Gastrectomy Fistulas
Authors: Sousa Patricia , Noronha Ferreira Carlos , Coutinho João , Carepa Fátima , Rosa Rosário , Barão Andreia , Marques Ferreira Carlos , Girao José , Ruivo António , Bicha Castelo Henrique , Lopes João , Almeida Amélia , Carrilho Ribeiro Luís , Velosa José
Published: September 2018

Background and Aims: Laparoscopic sleeve gastrectomy (LSG)-related fistulas are important and potentially fatal complications. We aimed at determining the incidence, predictive factors, and management of recurrence of post-LSG fistulas. Methods: This is a retrospective cohort study of 12 consecutive patients with LSG fistulas managed endoscopically between 2008 and 2013. We analyzed factors associated with recurrence of post-LSG fistulas and the efficacy of a primarily endoscopic approach to manage fistula recurrence. Results: The average age at fistula detection after LSG was 43.3 ± 10.9 years, and 10 (83%) patients were female. The median interval between surgery and initial fistula detection was 14 (4–145) days. Fistulas were located at the gastric cardia in 9/12 patients. A median of 4 (1–10) endoscopies were performed per patient until all fistulas were successfully closed. The median follow-up was 30.5 (15–72) months. Fistula recurrence was detected in 3 (25%) female patients with an average age of 31.7 ± 7.9 years after a median of 119 (50–205) days of the initial fistula closure. Fistulas in all 3 patients recurred at the gastric cardia and were successfully managed endoscopically. There was a second recurrence in 1 patient after 6 months, and she was re-operated with anastomosis of a jejunal loop at the site of the fistula orifice at the gastric cardia. We did not find any factors at initial fistula detection that were significantly associated with fistula recurrence. There were no deaths related to initial fistula after LSG and fistula recurrence. Conclusions: A primarily endoscopic approach is an effective and safe method for the management of fistulas after LSG. Fistula recurrence occurred in 25% of patients and was managed endoscopically. Key Messages: Although we could not define predictive factors of post-LSG fistula recurrence, it is a clinical reality and can be managed endoscopically.
In vitro Remote Aspiration Embolectomy for the Treatment of Acute Ischemic Stroke
Authors: Rizvi Asim , Fitzgerald Sean T. , Carlson Kent D. , Daescu Dan Dragomir , Brinjikji Waleed , Kadirvel Ramanathan , Kallmes David F.
Published: September 2018

Background: “Remote aspiration,” using suction from the proximal internal carotid artery (ICA) to open terminus occlusions, has been reported in small case series. However, it remains unclear whether remote aspiration is feasible for middle cerebral artery occlusions in the setting of potential inflow from communicating arteries. We performed an in vitro study to assess whether suction applied at various locations proximal to an occlusion could successfully aspirate the clot. Methods: A glass model of 4 mm inner diameter (ID) with 1 mm distal narrowing and 2 mm side branch to simulate a communicating artery was constructed. A proximal side branch was placed to simulate inflow from the proximal ICA. The impact of three different-sized catheters (ID 0.088, 0.070, and 0.056 in) on histologically different (red blood cell-cell rich, fibrin-rich, and mixed) clot analogues was tested with the catheter tip placed remotely either distal or proximal to the collateral branch. Aspiration was attempted with (1) open system (flow in both the ICA and the collateral branch, (2) flow arrest with open collateral (no flow in the ICA, but flow in the collateral branch), and (3) closed system (no flow in either the ICA or the collateral branch). The outcome was success or failure of remote aspiration. Results: For the 0.088-in catheter, remote aspiration was successful in all conditions. For the 0.070-in catheter, remote aspiration was unsuccessful without proximal flow arrest, but was successful in all other scenarios. For the 0.056-in catheter, remote aspiration was successful only with complete flow arrest. Conclusions: In a noncollapsible system, remote aspiration can be successfully achieved even in the setting of prominent branch arteries by using relatively large aspiration catheters. Proximal flow arrest may facilitate successful remote aspiration for some catheter sizes.
Pure Small Cell Carcinoma of Prostate: A Report of 8 Cases
Authors: Zhang Yucong , Ouyang Wei , Sun Guoliang , Ding Beichen , Yan Libin , Wang Zhize , Guan Wei , Li Heng , Hu Zhiquan , Xu Hua , Wang Shaogang , Ye Zhangqun
Published: September 2018

Purpose: To describe characteristics of pure small cell carcinoma of prostate (SCCP) and assess the prognostic factors. Patients and Methods: We summarized data of pure SCCP from published studies and ours and made Kaplan-Meier analysis and Cox regression to evaluate prognosis factors. Results: A total of 2,213 patients with prostate cancer was identified, of which eight (0.36%) patients were pure SCCP. The mean age at diagnosis was 61 years old. And there were 2 patients diagnosed at 34 and 50 years old respectively. Symptoms of these patients were similar to patients with prostate adenocarcinoma. Serum prostate specific antigen of 7 patients was at normal level. Five patients received chemotherapy, average overall survival (OS) was 9.75 months; 3 only received conservative treatment, average OS was 4 months. By univariate and multivariate Cox analysis, chemotherapy is an independent predictor of survival. Kaplan-Meier analysis demonstrated that chemotherapy was associated with longer OS. Conclusion: Clinical characteristics, examination and treatment strategy of pure SCCP are very different from prostate adenocarcinoma. According to the data from published studies and from our studies, the average survival of patients receiving chemotherapy is longer than those who received other treatment modalities.
Cost-Conscious Growth-Promoting Treatment: When Discretion Is the Better Part of Value
Authors: Allen David B.
Published: September 2018

Assessing cost-effectiveness of human growth hormone (hGH) treatment to augment height is complicated by uncertainty about how best to measure its therapeutic effect. Cost-conscious growth promotion practice, however, is possible and likely an emerging practical requisite as health care payers increasingly deny the medical necessity of and restrict support for short stature treatment. The increase in denials is not surprising given the expansion and continued high cost of hGH treatment, debate about the value of such treatment, and universal need to restrain burgeoning health care costs. Renunciation of sweeping payer rejection of hGH-for-height treatment is strengthened by cost-conscious practices that (1) recommend no treatment for most short children and restrict treatment to severe, likely disabling short stature; (2) initiate hGH treatment only after evidence-based informed assent; (3) utilize alternative less costly and less invasive options when possible; (4) minimize hGH treatment duration and dosage; and (5) resist enhancement of normal adult stature. A new era of cost-conscious hGH prescribing that prompts thoughtful restraint in hGH use could help preserve hGH approval for children most in need of treatment.
Familial Pancreatic Cancer
Authors: Benzel Julia , Fendrich Volker
Published: September 2018

Familial pancreatic cancer accounts for 10% of all patients with pancreatic cancer. Because the 5-year survival rate of pancreatic cancer is only 7%, screening programs for high-risk individuals are essential and might be advantageous. Pancreatic ductal adenocarcinoma mostly shows symptoms at an advanced state and treatment is not efficient enough to cure most patients. People with hereditary tumor syndromes or their affected relatives can also be included in such screening programs. Besides the collection of data to investigate the background of the disease, these screening programs aim to diagnose and treat precursor lesions so that more dangerous, invasive lesions are prevented. These precursor lesions can be pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. This review summarizes the latest knowledge of pancreatic screening programs, shows the procedure of pancreatic cancer screening, and gives an overview of current guidelines.
International Survey on the Management of Acute Kidney Injury and Continuous Renal Replacement Therapies: Year 2018
Authors: Digvijay Kumar , Neri Mauro , Fan Weixuan , Ricci Zaccaria , Ronco Claudio
Published: September 2018

Introduction: Definition, prevention, and management of acute kidney injury (AKI) and the optimal prescription and delivery of renal replacement therapy (RRT) are currently matters of ongoing discussion. Due to the lack of definitive published literature, a wide gap might exist between routine clinical practice and available recommendations. The aim of this survey was to explore the clinical approach to AKI and RRT in a broad population of nephrologists and intensivists participating in the 36th International course on AKI and Continuous RRT (CRRT), held in Vicenza in June 2018. The responses of the 369 participants to a questionnaire on several aspects of critical care nephrology were analyzed and detailed. Results: Approximately 450 participants attended the course; of these, 369 (82%) correctly filled the survey forms. According to the reported answers, the average incidence of AKI in respondents’ intensive care units (ICU) was 26.8% (SD ±15.99) and AKI requiring dialysis was 13% (SD ±29.7). Sixty-four percent of participants defined AKI as an increase in serum creatinine (SCr) up to 0.99 mg/dL (SD ±0.88 mg/dL); 2.4% defined AKI as an increase in urea nitrogen up to 83.6 mg/dL (SD ±36.6 mg/dL); 33.6% defined AKI as decreased urine output to less than 1 mL/kg/h (SD ±0.6 mL/kg/h). The most common answer to classify AKI was Kidney Disease: Improving Global Outcomes (KDIGO; 41%) criteria. Most of the participants (25%) think novel biomarkers should replace SCr on daily routine laboratory screening, and Cystatin C was the most commonly used biomarker (19%). The use of diuretics in AKI patients was high (62%). Continuous RRT (59%) and heparin anticoagulation (42%) appeared to be the most common approaches in ICU. Conclusions: KDIGO appeared to be widely applied. The use of novel biomarkers has also emerged in recent years even if some consistent cost-benefit evidence is still lacking. There is a trend of increased awareness about AKI and extracorporeal treatments seem to be increasingly applied, when compared to previous surveys. Educational efforts and AKI management standardization still appear to be a fundamental aspect to harmonize therapeutic approaches and improve patients’ outcomes.
Reinjury of Arterial Lesions Induces Intimal Smooth Muscle Cell Replication That Is Not Controlled by Fibroblast Growth Factor 2
Authors: Koyama Hiroyuki , Reidy Michael A.
Published: September 2018

In this study we have examined the response of rat carotid arteries with intimal lesions to an angioplasty injury. Rat carotid arteries were subjected to injury with a 2F Fogarty catheter (first injury), and 28 days later the same arteries were subjected to reinjury with a 1.5-mm-diameter coronary dilation catheter (second injury) or a sham operation. After the second injury, the injured arterial surfaces were covered by a platelet monolayer, with occasional small thrombi. The size of the intimal area was significantly increased 28 days after the second injury, although the luminal area was not changed at this time. Intimal and medial cell replication, measured by 5-bromo-2 prime-deoxyuridine labeling, was significantly increased at 2 days after the second injury but was markedly reduced by 7 days. Addition of fibroblast growth factor-2 (FGF2, 60 micro g IV) did not increase smooth muscle cell (SMC) replication in arteries subjected to the second injury, and replication was not inhibited with an antibody against FGF2 (120 mg IV). Both these reagents, however, did significantly affect SMC replication in normal carotid arteries subjected to Fogarty catheter injury. In a similar manner, heparin (888 UPS units/kg body wt IV) did not inhibit cell replication after second injury, although it did suppress SMC replication after a single injury. One conclusion is that rat intimal cells in vivo are different from medial SMCs and that other, as-yet-unknown, factors are important for their proliferation.
Organization and Sequence of Human Cardiac Myosin Binding Protein C Gene (MYBPC3) and Identification of Mutations Predicted to Produce Truncated Proteins in Familial Hypertrophic Cardiomyopathy
Authors: Carrier Lucie , Bonne Gisele , Bahrend Ellen , Yu Bing , Richard Pascale , Niel Florence , Hainque Bernard , Cruaud Corinne , Gary Francoise , Labeit Siegfried , Bouhour Jean-Brieuc , Dubourg Olivier , Desnos Michel , Hagege Albert A. , Trent Ronald J. , Komajda Michel , Fiszman Marc , Schwartz Ketty
Published: September 2018

Cardiac myosin binding protein C (MyBP-C) is a sarcomeric protein belonging to the intracellular immunoglobulin superfamily. Its function is uncertain, but for a decade evidence has existed for both structural and regulatory roles. The gene encoding cardiac MyBP-C (MYBPC3) in humans is located on chromosome 11p11.2, and mutations have been identified in this gene in unrelated families with familial hypertrophic cardiomyopathy (FHC). Detailed characterization of the MYBPC3 gene is essential for studies on gene regulation, analysis of the role of MyBP-C in cardiac contraction through the use of recombinant DNA technology, and mutational analyses of FHC. The organization of human MYBPC3 and screening for mutations in a panel of French families with FHC were established using polymerase chain reaction, single-strand conformation polymorphism, and sequencing. The MYBPC3 gene comprises >21 000 base pairs and contains 35 exons. Two exons are unusually small in size, 3 bp each. We found six new mutations associated with FHC in seven unrelated French families. Four of these mutations are predicted to produce truncated cardiac MyBP-C polypeptides. The two others should each produce two aberrant proteins, one truncated and one mutated. The present study provides the first organization and sequence for an MyBP-C gene. The mutations reported here and previously in MYBPC3 result in aberrant transcripts that are predicted to encode significantly truncated cardiac MyBP-C polypeptides. This spectrum of mutations differs from the ones previously observed in other disease genes causing FHC. Our data strengthen the functional importance of MyBP-C in the regulation of cardiac work and provide the basis for further studies.