bluuebunny/crossref_metadata_2025 huggingface dataset:
Meshless voronoi on the GPU
Authors: Ray Nicolas , Sokolov Dmitry , Lefebvre Sylvain , Lévy Bruno
Published: November 2018

We propose a GPU algorithm that computes a 3
D
Voronoi diagram. Our algorithm is tailored for applications that solely make use of the geometry of the Voronoi cells, such as Lloyd's relaxation used in meshing, or some numerical schemes used in fluid simulations and astrophysics. Since these applications only require the geometry of the Voronoi cells, they do not need the combinatorial mesh data structure computed by the classical algorithms (Bowyer-Watson). Thus, by exploiting the specific spatial distribution of the point-sets used in this type of applications, our algorithm computes each cell independently, in parallel, based on its nearest neighbors. In addition, we show how to compute integrals over the Voronoi cells by decomposing them on the fly into tetrahedra, without needing to compute any global combinatorial information. The advantages of our algorithm is that it is fast, very simple to implement, has constant memory usage per thread and does not need any synchronization primitive. These specificities make it particularly efficient on the GPU: it gains one order of magnitude as compared to the fastest state-of-the-art multi-core CPU implementations. To ease the reproducibility of our results, the full documented source code is included in the supplemental material.
Tracking the gaze on objects in 3D
Authors: Wang Xi , Koch Sebastian , Holmqvist Kenneth , Alexa Marc
Published: November 2018

We provide the first large dataset of human fixations on physical 3D objects presented in varying viewing conditions and made of different materials. Our experimental setup is carefully designed to allow for accurate calibration and measurement. We estimate a mapping from the pair of pupil positions to 3D coordinates in space and register the presented shape with the eye tracking setup. By modeling the fixated positions on 3D shapes as a probability distribution, we analysis the similarities among different conditions. The resulting data indicates that salient features depend on the viewing direction. Stable features across different viewing directions seem to be connected to semantically meaningful parts. We also show that it is possible to estimate the gaze density maps from view dependent data. The dataset provides the necessary ground truth data for computational models of human perception in 3D.
A radiative transfer framework for non-exponential media
Authors: Bitterli Benedikt , Ravichandran Srinath , Müller Thomas , Wrenninge Magnus , Novák Jan , Marschner Steve , Jarosz Wojciech
Published: November 2018

We develop a new theory of volumetric light transport for media with non-exponential free-flight distributions. Recent insights from atmospheric sciences and neutron transport demonstrate that such distributions arise in the presence of correlated scatterers, which are naturally produced by processes such as cloud condensation and fractal-pattern formation. Our theory formulates a non-exponential path integral as the result of averaging stochastic classical media, and we introduce practical models to solve the resulting averaging problem efficiently. Our theory results in a generalized path integral which allows us to handle non-exponential media using the full range of Monte Carlo rendering algorithms while enriching the range of achievable appearance. We propose parametric models for controlling the statistical correlations by leveraging work on stochastic processes, and we develop a method to combine such unresolved correlations (and the resulting non-exponential free-flight behavior) with explicitly modeled macroscopic heterogeneity. This provides a powerful authoring approach where artists can freely design the shape of the attenuation profile separately from the macroscopic heterogeneous density, while our theory provides a physically consistent interpretation in terms of a path space integral. We address important considerations for graphics including reciprocity and bidirectional rendering algorithms, all in the presence of surfaces and correlated media.
Interactive design of periodic yarn-level cloth patterns
Authors: Leaf Jonathan , Wu Rundong , Schweickart Eston , James Doug L. , Marschner Steve
Published: November 2018

We describe an interactive design tool for authoring, simulating, and adjusting yarn-level patterns for knitted and woven cloth. To achieve interactive performance for notoriously slow yarn-level simulations, we propose two acceleration schemes: (a) yarn-level periodic boundary conditions that enable the restricted simulation of only small periodic patches, thereby exploiting the spatial repetition of many cloth patterns in cardinal directions, and (b) a highly parallel GPU solver for efficient yarn-level simulation of the small patch. Our system supports interactive pattern editing and simulation, and runtime modification of parameters. To adjust the amount of material used (yarn take-up) we support "on the fly" modification of (a) local yarn rest-length adjustments for pattern specific edits, e.g., to tighten slip stitches, and (b) global yarn length by way of a novel yarn-radius similarity transformation. We demonstrate the tool's ability to support interactive modeling, by novice users, of a wide variety of yarn-level knit and woven patterns. Finally, to validate our approach, we compare dozens of generated patterns against reference images of actual woven or knitted cloth samples, and we release this corpus of digital patterns and simulated models as a public dataset to support future comparisons.
Factor once
Authors: Herholz Philipp , Alexa Marc
Published: November 2018

A common operation in geometry processing is solving symmetric and positive semi-definite systems on a subset of a mesh, with conditions for the vertices at the boundary of the region. This is commonly done by setting up the linear system for the sub-mesh, factorizing the system (potentially applying preordering to improve sparseness of the factors), and then solving by back-substitution. This approach suffers from a comparably high setup cost for each local operation. We propose to reuse factorizations defined on the full mesh to solve linear problems on sub-meshes. We show how an update on sparse matrices can be performed in a particularly efficient way to obtain the factorization of the operator on a sun-mesh significantly outperforming general factor updates and complete refactorization. We analyze the resulting speedup for a variety of situations and demonstrate that our method outperforms factorization of a new matrix by a factor of up to 10 while never being slower in our experiments.
Remote Detection of Unauthorized Activity via Spectral Analysis
Authors: Karabacak Fatih , Ogras Umit , Ozev Sule
Published: November 2018

Unauthorized hardware or firmware modifications, known as trojans, can steal information, drain the battery, or damage IoT devices. Since trojans may be triggered in the field at an unknown instance, it is important to detect their presence at runtime. However, it is difficult to run sophisticated detection algorithms on these devices due to limited computational power and energy and, in some cases, lack of accessibility. This article presents a stand-off self-referencing technique for detecting unauthorized activity. The proposed technique processes involuntary electromagnetic emissions on a separate hardware, which is physically decoupled from the device under test.
When the device enters the test mode
, a predefined test application is run on the device repetitively for a known period. The periodicity ensures that the spectral electromagnetic power of the test application concentrates at known frequencies, leaving the remaining frequencies within the operating bandwidth at the noise level. Any deviations from the noise level for these unoccupied frequency locations indicate the presence of unknown (unauthorized) activity. Hence, we are able to differentiate trojan activity
without using a golden reference
, or any knowledge of the attributes of the trojan activity. Experiments based on hardware measurements show that the proposed technique achieves close to 100% detection accuracy at up to 120cm distance.
The Fokker–Planck Approach to Complex Spatiotemporal Disordered Systems
Authors: Peinke J. , Tabar M.R.R. , Wächter M.
Published: November 2018

When the complete understanding of a complex system is not available, as, e.g., for systems considered in the real world, we need a top-down approach to complexity. In this approach, one may desire to understand general multipoint statistics. Here, such a general approach is presented and discussed based on examples from turbulence and sea waves. Our main idea is based on the cascade picture of turbulence, entangling fluctuations from large to small scales. Inspired by this cascade picture, we express the general multipoint statistics by the statistics of scale-dependent fluctuations of variables and relate it to a scale-dependent process, which finally is a stochastic cascade process. We show how to extract from empirical data a Fokker–Planck equation for this cascade process, which allows the generation of surrogate data to forecast extreme events as well as to develop a nonequilibrium thermodynamics for the complex systems. For each cascade event, an entropy production can be determined. These entropies accurately fulfill a rigorous law, namely the integral fluctuations theorem.
System Identification: A Machine Learning Perspective
Authors: Chiuso A. , Pillonetto G.
Published: November 2018

Estimation of functions from sparse and noisy data is a central theme in machine learning. In the last few years, many algorithms have been developed that exploit Tikhonov regularization theory and reproducing kernel Hilbert spaces. These are the so-called kernel-based methods, which include powerful approaches like regularization networks, support vector machines, and Gaussian regression. Recently, these techniques have also gained popularity in the system identification community. In both linear and nonlinear settings, kernels that incorporate information on dynamic systems, such as the smoothness and stability of the input–output map, can challenge consolidated approaches based on parametric model structures. In the classical parametric setting, the complexity of the model (the model order) needs to be chosen, typically from a finite family of alternatives, by trading bias and variance. This (discrete) model order selection step may be critical, especially when the true model does not belong to the model class. In regularization-based approaches, model complexity is controlled by tuning (continuous) regularization parameters, making the model selection step more robust. In this article, we review these new kernel-based system identification approaches and discuss extensions based on nuclear and [Formula: see text] norms.
The Platelet Napoleon Complex—Small Cells, but Big Immune Regulatory Functions
Authors: Morrell Craig N. , Pariser Daphne N. , Hilt Zachary T. , Vega Ocasio Denisse
Published: November 2018

Platelets have dual physiologic roles as both cellular mediators of thrombosis and immune modulatory cells. Historically, the thrombotic function of platelets has received significant research and clinical attention, but emerging research indicates that the immune regulatory roles of platelets may be just as important. We now know that in addition to their role in the acute thrombotic event at the time of myocardial infarction, platelets initiate and accelerate inflammatory processes that are part of the pathogenesis of atherosclerosis and myocardial infarction expansion. Furthermore, it is increasingly apparent from recent studies that platelets impact the pathogenesis of many vascular inflammatory processes such as autoimmune diseases, sepsis, viral infections, and growth and metastasis of many types of tumors. Therefore, we must consider platelets as immune cells that affect all phases of immune responses.
Research on Work as a Calling…and How to Make It Matter
Authors: Thompson Jeffery A. , Bunderson J. Stuart
Published: November 2018

The concept of work as a calling has the potential to provide unique and powerful insights into how individuals relate to their work and organizations. However, although this concept may be one of the oldest in the study of work—harking back to the Protestant Reformation—its impact on mainstream OP and OB research has been limited. We review the research literature on work as a calling, and identify several issues that are preventing research in this area from reaching its potential—issues of definition, differentiation, generalizability, and relevance. We consider each of these questions and propose a path forward. Central to that path forward is an integrated conceptualization of calling—what we call a transcendent calling—that puts dual emphasis on the inner requiredness of passion and enjoyment and the outer requiredness of duty and destiny.
Cellular Metabolism in Lung Health and Disease
Authors: Liu Gang , Summer Ross
Published: November 2018

The lung is often overlooked as a metabolically active organ, yet biochemical studies have long demonstrated that glucose utilization surpasses that of many other organs, including the heart, kidney, and brain. For most cells in the lung, energy consumption is relegated to performing common cellular tasks, like mRNA transcription and protein translation. However, certain lung cell populations engage in more specialized types of energy-consuming behaviors, such as the beating of cilia or the production of surfactant. While many extrapulmonary diseases are now linked to abnormalities in cellular metabolism, the pulmonary community has only recently embraced the concept of metabolic dysfunction as a driver of respiratory pathology. Herein, we provide an overview of the major metabolic pathways in the lung and discuss how cells sense and adapt to low-energy states. Moreover, we review some of the emerging evidence that links alterations in cellular metabolism to the pathobiology of several common respiratory diseases.
Mitochondrial Iron in Human Health and Disease
Authors: Ward Diane M. , Cloonan Suzanne M.
Published: November 2018

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. In recent years, cellular and animal models of mitochondrial iron dysfunction have provided vital information in identifying new proteins that have elucidated the pathways involved in mitochondrial homeostasis and iron metabolism. Specific signatures of mitochondrial iron dysregulation that are associated with disease pathogenesis and/or progression are becoming increasingly important. Understanding the molecular mechanisms regulating mitochondrial iron pathways will help better define the role of this important metal in mitochondrial function and in human health and disease.
Carnosine modulates the Sp1-Slc31a1/Ctr1 copper-sensing system and influences copper homeostasis in murine CNS-derived cells
Authors: Barca Amilcare , Ippati Stefania , Urso Emanuela , Vetrugno Carla , Storelli Carlo , Maffia Michele , Romano Alessandro , Verri Tiziano
Published: November 2018

Carnosine (CAR) is an endogenous dipeptide physiologically present in excitable tissues, such as central nervous system (CNS) and muscle. CAR is acknowledged as a substrate involved in many homeostatic pathways and mechanisms and, due to its biochemical properties, as a molecule intertwined with the homeostasis of heavy metals such as copper (Cu). In CNS, Cu excess and dysregulation imply oxidative stress, free-radical production, and functional impairment leading to neurodegeneration. Here, we report that CAR intercepts the regulatory routes of Cu homeostasis in nervous cells and tissues. Specifically, in a murine neuron-derived cell model, i.e., the B104 neuroblastoma cells, extracellular CAR exposure up to 24 h influenced intracellular Cu entry and affected (downregulated) the key Cu-sensing system, consisting of the gene coding for the Slc31a1 transmembrane Cu importer (alias Ctr1), and the gene coding for the Cu-responsive transcription factor Sp1 ( Sp1). Also, CAR exposure upregulated CAR biosynthesis ( Carns1), extracellular degradation ( Cndp1), and transport ( Slc15a4, alias Pht1) genes and elicited CAR intracellular accumulation, contributing to the outline of functional association between CAR and Cu within the cell. Interestingly, the same gene modulation scheme acting in vitro operates in vivo in brains of mice undergoing dietary administration of CAR in drinking water for 2 wk. Overall, our findings describe for the first time a regulatory interaction between CAR and Cu pathways in CNS and indicate CAR as a novel active molecule within the network of ligands and chaperones that physiologically regulate Cu homeostasis.
Temporal resolution of single-photon responses in primate rod photoreceptors and limits imposed by cellular noise
Authors: Field Greg D. , Uzzell Valerie , Chichilnisky E. J. , Rieke Fred
Published: November 2018

Sensory receptor noise corrupts sensory signals, contributing to imperfect perception and dictating central processing strategies. For example, noise in rod phototransduction limits our ability to detect light, and minimizing the impact of this noise requires precisely tuned nonlinear processing by the retina. But detection sensitivity is only one aspect of night vision: prompt and accurate behavior also requires that rods reliably encode the timing of photon arrivals. We show here that the temporal resolution of responses of primate rods is much finer than the duration of the light response and identify the key limiting sources of transduction noise. We also find that the thermal activation rate of rhodopsin is lower than previous estimates, implying that other noise sources are more important than previously appreciated. A model of rod single-photon responses reveals that the limiting noise relevant for behavior depends critically on how rod signals are pooled by downstream neurons.

NEW & NOTEWORTHY Many studies have focused on the visual system’s ability to detect photons, but not on its ability to encode the relative timing of detected photons. Timing is essential for computations such as determining the velocity of moving objects. Here we examine the timing precision of primate rod photoreceptor responses and show that it is more precise than previously appreciated. This motivates an evaluation of whether scotopic vision approaches limits imposed by rod temporal resolution.
Antibacterial Activity and Cytotoxic Effect of Pelargonium peltatum (Geranium) against Streptococcus mutans and Streptococcus sanguinis
Authors: Coronado-López Samantha , Caballero-García Stefany , Aguilar-Luis Miguel Angel , Mazulis Fernando , del Valle-Mendoza Juana
Published: November 2018

Objective. To evaluate the in vitro antibacterial and cytotoxic properties of the methanolic extract of Pelargonium peltatum (geranium) against Streptococcus mutans (ATCC 25175) and Streptococcus sanguinis (ATCC 10556). Methods. Three extracts of P. peltatum were prepared using the leaf, stem, and root. Nine independent assays were prepared for each type of extract with chlorhexidine at 0.12% as the positive control. The agar diffusion method was performed to determine the antibacterial properties of each extract. The minimum inhibitory concentration (MIC) was determined using the microdilution method, and the cytotoxicity was analyzed by means of the MTT reduction test using a MDCK cell line. Results. The root extract had the highest antibacterial effect with a mean result of (27.68 ± 0.97) mm and (30.80 ± 0.55) mm against S. mutans and S. sanguinis, respectively. The minimum inhibitory concentration for the leaf and root extracts was 250 mg/mL for S. mutans and 125 mg/mL for S. sanguinis. Cytotoxicity assays showed that both extracts had a low cytotoxicity at high concentrations. The cellular viability was highest for the root extract at 95.3% followed by the stem extract at 80.8% and finally the leaf extract with 75.4%. Conclusions. These findings show the antibacterial properties of the methanolic extracts of P. pelargonium against S. mutans and S. sanguinis. These extracts were not cytotoxic at high concentrations.
Existence and Stability of Periodic Solution Related to Valveless Pumping
Authors: Dorociaková B. , Michalková M. , Olach R. , Sága M.
Published: November 2018

Valveless pumping, also known as Liebau effect, can be described as the unidirectional flow of liquid in a system without valves that is caused by the asymmetry of placing of the periodically working pump. Recently, the research in this field has been reevoked, partially due to its possible application in nanotechnologies. In this paper, a configuration of one pipe and one tank is considered from the mathematical point of view. Qualitative properties of a class of nonlinear differential equations that model the assumed system configuration are investigated. New sufficient conditions for the existence of positive T-periodic solutions are given. Correspondingly, exponential stability of periodic solution is treated. Presented results are new. They extend and complement earlier ones in the literature.
Chronic Periodontitis Case Definitions and Confounders in Periodontal Research: A Systematic Assessment
Authors: Natto Zuhair S. , Abu Ahmad Randa H. , Alsharif Lina T. , Alrowithi Hanan F. , Alsini Duaa A. , Salih Hetaf A. , Bissada Nabil F.
Published: November 2018

Case definitions and criteria of periodontal diseases are not yet consistent worldwide. This can affect the accuracy of any comparison made between two studies. This study determines which are the most common chronic periodontitis case definitions as well as confounding variables that have been reported worldwide in periodontal literature. A systematic assessment on periodontal disease classification and confounders was conducted using all publications in MEDLINE, EMBASE, SCOPUS, and Google Scholar between 1965 and October 2017. Screening of eligible studies and data extraction were conducted in duplicate and independently by two reviewers. The search protocol produced 4,218 articles. Out of these, 492 potentially relevant articles were selected for review. Only 351 studies fulfilled the selection criteria. Combination of probing depth and clinical attachment loss was the most common chronic periodontitis case definitions used (121, studies, 34.5%). CPI/CPITN was the most common classification used. Age was the most common confounder studied in periodontal research (303 studies, 86.3%), followed by gender (268 studies, 76.4%) and race (138 studies, 39.3%). Albumin and creatinine were the least common variables studied (1 or 2 studies each). Different case definitions affect the prevalence and treatment consequences of periodontitis. We need to standardize periodontitis case definitions worldwide to avoid difficulties in case diagnosis and prognosis. Further studies need to be done to assess the association between periodontitis and several potential confounders.
Use of Flavonoids and Cinnamates, the Main Photoprotectors with Natural Origin
Authors: Nunes Alesandra R. , Vieira Ícaro G. P. , Queiroz Dinalva B. , Leal Antonio Linkoln Alves Borges , Maia Morais Selene , Muniz Débora Feitosa , Calixto-Junior João Tavares , Coutinho Henrique Douglas Melo
Published: November 2018

Many pathological problems are initiated by ultraviolet radiation (UVR), such as skin cancer, the most commonly diagnosed cancer worldwide. The UVA (320–400 nm) and UVB (290–320 nm) wavelengths may cause effects such as photoaging, DNA damage, and a series of cellular alterations. The UVA radiation can damage the DNA, oxidize the lipids, and produce dangerous free radicals, which can cause inflammation, modify the gene expression in response to stress, and weaken the skin immune response. With a minor penetration, the UVB radiation is more harmful, being responsible for immediate damage. Ultraviolet radiation light emitted by the sun is considered necessary for the existence of life but cause radiation problems, especially in the skin. The photoprotective activities of plant extracts and isolated composts were evaluated by many reports, as well as the correlation of these compounds with the antioxidant activity. This review presents plant compounds with interest to the cosmetic industry to be used in sunscreens such as flavonoids and cinnamates.
In Vitro Evaluation of Antimicrobial Activity and Cytotoxicity of Different Nanobiotics Targeting Multidrug Resistant and Biofilm Forming Staphylococci
Authors: Mohamed Mennatallah A. , Nasr Maha , Elkhatib Walid F. , Eltayeb Wafaa N.
Published: November 2018

Antibiotic-resistant and biofilm-forming bacteria have surprisingly increased over recent years. On the contrary, the rate of development of new antibiotics to treat these emerging superbugs is very slow. Therefore, the aim of this study was to prepare novel nanobiotic formulations to improve the antimicrobial activity of three antibiotics (linezolid, doxycycline, and clindamycin) against Staphylococci. Antibiotics were formulated as nanoemulsions and evaluated for their antimicrobial activities and cytotoxicities. Cytotoxicity of the conventional antibiotics and nanobiotics was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on rat hepatocytes. Half-maximal inhibitory concentration (IC50) was estimated from an experimentally derived dose-response curve for each concentration using GraphPad Prism software. Upon quantitative assessment of Staphylococcus biofilm formation, eighty-four isolates (66.14 %) were biofilm forming. Linezolid and doxycycline nanobiotics exhibited promising antibacterial activities. On the contrary, clindamycin nanobiotic exhibited poor antibacterial activity. Minimum biofilm inhibitory concentrations showed that 73.68 %, 45.6%, and 5.2% of isolates were sensitive to linezolid, doxycycline, and clindamycin nanobiotics, respectively. Results of this study revealed that antibiotics loaded in nanosystems had a higher antimicrobial activity and lower cytotoxicities as compared to those of conventional free antibiotics, indicating their potential therapeutic values.
Tsantan Sumtang Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Inhibiting Proliferation of Pulmonary Vascular Cells
Authors: He Qilian , Nan Xingmei , Li Silin , Su Shanshan , Ma Ke , Li Zhanqiang , Lu Dianxiang , Ge Rili
Published: November 2018

Hypoxia-induced pulmonary hypertension (HPH) is a severe condition associated with significant morbidity and mortality in people living at high altitude. Tsantan Sumtang, a traditional Tibetan medicine, has been routinely used for the treatment of cardiopyretic disease, as well as stenocardia. Interestingly, our previous research found that Tsantan Sumtang improved HPH in rats maintaining in a hypobaric chamber. We performed a series of experiments to test the indexes of vasoconstriction and vascular remodeling, the key pathophysiological characteristics of HPH. Our results showed that Tsantan Sumtang relaxed noradrenaline (NE)-precontracted rat pulmonary artery rings in a concentration-dependent manner in vitro. The PGI2-cAMP (prostaglandin I2-cyclic adenosine monophosphate) pathway, NO-cGMP (nitric oxide-cyclic guanosine monophosphate) pathway, and the opening of K+ channels (inward rectifier K+ channels, large conductance Ca2+-activated K+ channels, and voltage-dependent K+ channels) might play major roles in the vasorelaxation effect. In vivo, the administration of Tsantan Sumtang resulted in a substantial decrease in the rat mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index (RVHI). The reduction of thickness of small pulmonary arterial wall and the WT% (the ratio of the vascular wall thickness to the vascular diameter) were observed. The smooth muscle muscularization of the arterials was alleviated by Tsantan Sumtang treatment at the same time. Tsantan Sumtang also reduced remodeling of pulmonary arterioles by suppressing the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), cyclin D1, and cyclin-dependent kinase 4 (CDK4) through inhibition of p27Kip1 degradation. Therefore, Tsantan Sumtang could be applied as a preventative medication for HPH, which would be a new use for this traditional medicine.
Ribosomal Lesions Promote Oncogenic Mutagenesis
Authors: Sulima Sergey O. , Kampen Kim R. , Vereecke Stijn , Pepe Daniele , Fancello Laura , Verbeeck Jelle , Dinman Jonathan D. , De Keersmaecker Kim
Published: November 2018

Ribosomopathies are congenital disorders caused by mutations in ribosomal proteins (RP) or assembly factors and are characterized by cellular hypoproliferation at an early stage. Paradoxically, many of these disorders have an elevated risk to progress to hyperproliferative cancer at a later stage. In addition, somatic RP mutations have recently been identified in various cancer types, for example, the recurrent RPL10-R98S mutation in T-cell acute lymphoblastic leukemia (T-ALL) and RPS15 mutations in chronic lymphocytic leukemia (CLL). We previously showed that RPL10-R98S promotes expression of oncogenes, but also induces a proliferative defect due to elevated oxidative stress. In this study, we demonstrate that this proliferation defect is eventually rescued by RPL10-R98S mouse lymphoid cells that acquire 5-fold more secondary mutations than RPL10-WT cells. The presence of RPL10-R98S and other RP mutations also correlated with a higher mutational load in patients with T-ALL, with an enrichment in NOTCH1-activating lesions. RPL10-R98S–associated cellular oxidative stress promoted DNA damage and impaired cell growth. Expression of NOTCH1 eliminated these phenotypes in RPL10-R98S cells, in part via downregulation of PKC-θ, with no effect on RPL10-WT cells. Patients with RP-mutant CLL also demonstrated a higher mutational burden, enriched for mutations that may diminish oxidative stress. We propose that oxidative stress due to ribosome dysfunction causes hypoproliferation and cellular insufficiency in ribosomopathies and RP-mutant cancer. This drives surviving cells, potentiated by genomic instability, to acquire rescuing mutations, which ultimately promote transition to hyperproliferation.

Significance:

Ribosomal lesions cause oxidative stress and increase mutagenesis, promoting acquisition of rescuing mutations that stimulate proliferation.
A Population-Based Study on Liver Metastases in Women with Newly Diagnosed Breast Cancer
Authors: Xie Jingjing , Xu Zhongyuan
Published: November 2018

Background:

Population-based estimates for prognosis among patients with liver metastases in newly diagnosed breast cancer are not generally available.

Methods:

Within the Surveillance, Epidemiology and End Results (SEER) database, we identified 298,370 patients with breast cancer and 4,285 patients diagnosed with initial liver metastases between 2010 and 2014. Data were stratified according to subtype, age, and race. Multivariate logistic and Cox regression were used to identify predictors for the presence of initial liver metastases and prognostic factors, respectively. Kaplan–Meier procedure was used for survival analysis.

Results:

A total of 4,285 patients with initial liver metastases (1.4% of the entire cohort, 29.6% of the subset with metastatic disease) were identified. Patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (4.4% of entire cohort, 52.5% of patients with metastatic disease to any distant site) and HR-positive HER2-positive (2.8% of entire cohort, 40.4% of patients with metastatic disease to any distant site) subtypes had highest incidence proportions. The median survival of patients with liver metastases in the entire cohort was 15.0 months. Patients with HR-positive HER2-positive subtype showed the longest median survival (31.0 months); however, patients with triple-negative subtype showed the shortest median survival (8.0 months).

Conclusions:

Our findings provide population-based estimates of epidemiologic characteristics and prognosis in breast cancer patients diagnosed with initial liver metastases.

Impact:

This study lends support to the diagnosis of the liver among patients at high risk of liver metastases, including those with HER2-positive and other systemic metastases.
PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma
Authors: de Vicente Juan C. , Rodríguez-Santamarta Tania , Rodrigo Juan P. , Blanco-Lorenzo Verónica , Allonca Eva , García-Pedrero Juana M.
Published: November 2018

Background:

The immune checkpoint PD-1 and its ligand PD-L1 are involved in the induction of immunological tolerance of solid tumors including oral squamous cell carcinoma (OSCC). The aim of the study was to establish the clinical and prognostic significance of PD-L1 in OSCC.

Methods:

Tissue microarrays of 125 resected OSCC were stained with two different commercially available PD-L1 antibodies (clones E1L3N and 22C3), alongside PD-1 immunostaining.

Results:

PD-L1 expression in more than 10% of tumor cells was associated with poorer survival, and established as a clinically relevant cut-off point. This relevant PD-L1 expression was detected in 10% to 15% OSCC specimens depending on the anti-PD-L1 antibody, and showed an inverse correlation with tobacco and alcohol consumption. We consistently found that PD-L1 expression was associated with tumor recurrence and lower disease-specific survival. Multivariate analysis further revealed that neck node metastasis (HR 2.304; P = 0.009) and tumor PD-L1 expression (HR 2.571; P = 0.01) were significant independent factors for poor prognosis.

Conclusions:

PD-L1 expression in more than 10% of tumor cells was a significant and independent factor of poor prognosis in OSCC.

Impact:

PD-L1 expression in more than 10% of tumor cells was consistently established as a clinically relevant cut-off point by using two different antibodies. Remarkably, PD-L1 expression emerges as an independent poor prognosis marker in patients with OSCC.
Internalization of Exosomes through Receptor-Mediated Endocytosis
Authors: Gonda Amber , Kabagwira Janviere , Senthil Girish N. , Wall Nathan R.
Published: November 2018

The tumor microenvironment is replete with factors secreted and internalized by surrounding cells. Exosomes are nano-sized, protein-embedded, membrane-bound vesicles that are released in greater quantities from cancer than normal cells and taken up by a variety of cell types. These vesicles contain proteins and genetic material from the cell of origin and in the case of tumor-derived exosomes, oncoproteins and oncogenes. With increasing understanding of the role exosomes play in basic biology, a more clear view of the potential exosomes are seen to have in cancer therapeutics emerges. However, certain essential aspects of exosome function, such as the uptake mechanisms, are still unknown. Various methods of cell–exosome interaction have been proposed, but this review focuses on the protein–protein interactions that facilitate receptor-mediated endocytosis, a broadly used mechanism by a variety of cells.
Endoscopic Ultrasound-Guided Gallbladder Drainage for Aberrant Right Posterior Duct Obstruction Developing after Placement of a Covered Self-Expandable Metallic Stent in a Patient with Distal Biliary Obstruction
Authors: Suzuki Yuko , Hashimoto Yusuke , Shibuki Taro , Kan Motoyasu , Kimura Gen , Umemoto Kumiko , Watanabe Kazuo , Sasaki Mitsuhito , Takahashi Hideaki , Imaoka Hiroshi , Ohno Izumi , Mitsunaga Shuichi , Ikeda Masafumi
Published: November 2018

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been utilized as an alternative endoscopic technique for patients with acute cholecystitis. In addition to EUS-guided hepaticogastrostomy and EUS-guided cystogastrostomy, EUS-GBD has been reported as being useful for biliary drainage in cases with distal malignant biliary obstruction instead of conventional endoscopic retrograde cholangiopancreatography. We present a case of successful EUS-GBD for malignant obstruction of an aberrant hepatic duct draining directly into the cystic duct.
Hepatosplenic T-Cell Lymphoma: A Rare Complication of Monotherapy with Thiopurines in Crohn’s Disease
Authors: Carvão Joana , Magno Pereira Vítor , Jacinto Fernando , Sousa Andrade Carla , Jasmins Luís
Published: November 2018

Hepatosplenic T-cell lymphoma (HSTCL) is an extremely rare and aggressive form of non-Hodgkin lymphoma associated with poor response to treatment and high mortality. There is an increased incidence among patients with inflammatory bowel disease, especially young male patients under 35 years old and on combination therapy (thiopurine and anti-TNF-α). We describe a case of HSTCL in a young male patient with stenosing ileal Crohn’s disease on azathioprine monotherapy for 4.8 years admitted to our hospital with intra- abdominal sepsis. Despite chemotherapy, the patient eventually died 1 month after the diagnosis. Through a literature review, we identified 18 additional cases of HSTCL in Crohn’s disease patients that had only been treated with thiopurine monotherapy. The authors intend to highlight the rarity of this diagnosis especially with azathioprine monotherapy and the diagnostic challenge in a case that presented with intra-abdominal sepsis.
Towards the Quantification of Peggy Babcock: Speech Errors and Their Position within the Word
Authors: Mooshammer Christine , Tiede Mark , Shattuck-Hufnagel Stefanie , Goldstein Louis
Published: November 2018

Sequences of similar (i.e., partially identical) words can be hard to say, as indicated by error frequencies, longer reaction and execution times. This study investigates the role of the location of this partial identity and the accompanying differences, i.e. whether errors are more frequent with mismatches in word onsets (top cop), codas (top tock) or both (pop tot). Number of syllables (tippy ticky) and empty positions (top ta) were also varied. Since the gradient nature of errors can be difficult to determine acoustically, articulatory data were investigated. Articulator movements were recorded using electromagnetic articulography, for up to 9 speakers of American English repeatedly producing 2-word sequences to an accelerating metronome. Most word pairs showed more intrusions and greater variability in coda than in onset position, in contrast to the predominance of onset position errors in corpora from perceptual observation.
The Ratio Serum Creatinine/Serum Cystatin C (a Surrogate Marker of Muscle Mass) as a Predictor of Hospitalization in Chronic Obstructive Pulmonary Disease Outpatients
Authors: Amado Carlos Antonio , García-Unzueta Maria Teresa , Lavin Bernardo Alio , Guerra Armando Raúl , Agüero Juan , Ramos Laura , Muñoz Pedro
Published: November 2018

Background: In chronic obstructive pulmonary disease (COPD), low muscle mass has been associated with several clinical outcomes such as low exercise capacity, hospital admission, and mortality. The Sarcopenia Index (SI) is a novel way to estimate muscle mass based on the ratio of serum creatinine (produced exclusively by muscle)/cystatin C (produced by all nucleated body cells). Objectives: This study aims to assess the SI in stable COPD outpatients, as compared with a healthy control group, to quantify its relationship with several important clinical features in COPD, and to study its potential usefulness to predict COPD exacerbations and hospital admissions. Methods: The SI was calculated in 18 healthy control subjects and 65 stable COPD outpatients were included in the study. Patients were prospectively followed for 1 year after being enrolled in the study. Results: COPD patients had a lower SI than controls, that is lower muscle mass. Furthermore, patients with a modified Medical Research Council dyspnea score ≥2, patients with a COPD Assessment Test score ≥10, and patients with a high risk of exacerbation had lower levels of SI compared with patients without these characteristics. SI correlated with FEV1 (r = 0.491, p < 0.001), the 6-min walking test (r = 0.560, p = 0.001), and the Fat-Free Mass Index (r = 0.431, p = 0.017). Univariate and multivariate Cox proportional risk analysis showed that a low SI is an independent predictor of hospital admission in COPD outpatients followed for 1 year (HR 5.16, p = 0.025). Conclusions: The ratio serum creatinine/serum cystatin C correlates with several COPD characteristics, and it can be used to predict COPD hospitalization.
Spontaneous Remission of Diffuse Large B Cell Lymphoma in the Stomach and the Continuation of Remission for 10 Years
Authors: Sugiyama Toshiro , Arita Kotaro , Shinno Eiji , Nakajima Takahiko
Published: November 2018

According to the literature, spontaneous remission of aggressive lymphomas is extremely rare; gastric non-Hodgkin lymphomas, such as mucosa-associated lymphoid tissue lymphomas, often regress due to Helicobacter pylori treatment or no progression, even in a watch-and-wait strategy. Although spontaneous remission of diffuse large B cell lymphomas in the stomach was very rarely reported, the follow-up periods of the cases of spontaneous remission are within 2 years and most cases are likely to relapse after the first remission. Here, we report that a diffuse large B cell lymphoma in the stomach showed spontaneous remission within 2 months after the initial diagnosis and the remission is still continuing for 10 years without any specific treatments against this aggressive lymphoma.
Skeletal Morbidity in Children and Adolescents during and following Cancer Therapy
Authors: Mostoufi-Moab Sogol , Ward Leanne M.
Published: November 2018

Skeletal abnormalities are common in children and adolescents diagnosed and treated for a malignancy. The spectrum ranges from mild pain to debilitating osteonecrosis and fractures. In this review, we summarize the impact of cancer therapy on the developing skeleton, provide an update on therapeutic strategies for prevention and treatment, and discuss the most recent advances in musculoskeletal research. Early recognition of skeletal abnormalities and strategies to optimize bone health are essential to prevent long-term skeletal sequelae and diminished quality of life in childhood cancer survivors.
Gastric Outlet Obstruction due to Intramural Duodenal Hematoma after Endoscopic Biopsy: Possible Therapeutic Role of Endoscopic Dilation
Authors: Samra Mahmud , Al-Mouradi Tarek , Berkelhammer Charles
Published: November 2018

Intramural duodenal hematoma (IDH) is an extremely rare complication after endoscopic biopsy. It typically presents with symptoms due to duodenal obstruction, which include abdominal pain and bilious vomiting. The hematoma may also expand and cause ampullary compression leading to pancreatitis and cholestasis. Computed tomography scan and abdominal ultrasound are the most common diagnostic modalities. Treatment is usually conservative, with bowel rest, nasogastric suctioning and total parenteral nutrition. Refractory cases have been described, requiring endoscopic therapy or surgical drainage. We describe a 28-year-old healthy male who presented with acute abdominal pain a few hours after a routine esophagogastrodudenoscopy with biopsies was performed. Following an otherwise uneventful endoscopy, he developed a gastric outlet obstruction and pancreatitis secondary to an IDH. The patient was managed conservatively. Resolution of his gastric outlet obstruction occurred immediately after gentle passage of the endoscope through the narrowed duodenal lumen.
Intensive Statin Therapy for Acute Ischemic Stroke to Reduce the Number of Microemboli: A Preliminary, Randomized Controlled Study
Authors: Chen Xingyu , Zhuang Xiaorong , Peng Zhongwei , Yang Huili , Chen Liangyi , Yang Qingwei
Published: November 2018

Background: To assess whether intensive statin therapy reduces the occurrence of microemboli in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke within 72 h of onset were randomized to the intensive statin (atorvastatin 60 mg/day, adjusted to 20 mg/day after 7 days) and control (atorvastatin 20 mg/day) groups. Combined aspirin and clopidogrel were used for antiplatelet therapy. Microemboli were monitored by transcranial Doppler on days 1 (pre-treatment), 3, and 7. Metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hs-CRP), and National Institutes of Health Stroke Scale (NIHSS) score were assessed on days 1 and 7. The modified Rankin scale (mRS) was used on day 90. The primary outcome was the proportion of patients with microemboli on day 3. Results: There were 35 (58.3%) and 30 (52.6%) patients with microemboli in the intensive statin (n = 60) and control (n = 57) groups, respectively, on day 1 (p = 0.342). On day 3, there were significantly less microemboli in the intensive statin group (n = 9; 15.0%) compared with controls (n = 16; 28.1%; p = 0.002). No difference was observed in MMP-9 and hs-CRP levels on day 1, but on day 7, MMP-9 (median 79.3 vs. 95.9 μg/L; p = 0.004) and hs-CRP (median 2.01 vs. 3.60 mg/L; p = 0.020) levels were lower in the intensive statin group compared with controls. There were no differences in NIHSS scores on days 1 and 7. There was no difference in mRS on day 90. Conclusion: Intensive atorvastatin therapy in patients with acute ischemic stroke reduces the occurrence of microemboli and inflammation, with no overt adverse events.
Delayed Diagnosis of Vulvar Crohn’s Disease in a Patient with No Gastrointestinal Symptoms
Authors: Wells Leah Ellis , Cohen David
Published: November 2018

Though Crohn’s disease primarily affects the gastrointestinal tract, cutaneous Crohn’s disease of the vulva can occur in the absence of gastrointestinal symptoms, complicating the diagnosis. Once clinicians suspect cutaneous Crohn’s disease, antibiotics and traditional immunosuppressants comprise initial treatment. Unfortunately, sometimes these therapies are not effective, or they provide only short-lived symptomatic improvement. A few case reports have found tumor necrosis factor-α inhibitors to be helpful in such refractory cases. We describe a patient with long-standing, painful vulvar Crohn’s lesions with no gastrointestinal manifestations of the disease. Her diagnosis was delayed for years, and initial therapy with antibiotics and steroids was unsuccessful. Finally, the patient experienced effective and long-lasting symptom improvement with infliximab (RemicadeTM).
Keloid Formation due to Repetitive Mammographies
Authors: Pruimboom Tim , Scheltinga Marc R.
Published: November 2018

A keloid is the result of an abnormal wound healing response to a variety of skin injuries, characterized by a well-circumscribed, firm, irregular, mildly tender, and pink to purple hyperpigmented lump with a glossy surface. The present case reports on excessive formation of keloid due to repetitive mammographies causing symptomatic, cosmetically disturbing symptoms.