bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and academic integration strategies for retention of nursing students: a scoping review protocol
Authors: Mitchell Kim M. , Chorney Meagen A. , Gural Deborah M. , Simmons-Swinden Joanna M. , Picheca Lory , Baxter Catherine E.
Published: January 2019

Review question:

The review question is: what are the types of formal and informal social and academic integration strategies that have been explored to influence nursing student persistence and increase retention in nursing programs? A secondary review objective is to address how the described strategies have specifically been implemented with minority nursing students.
Defining the caudal hypothalamic arcuate nucleus with a focus on anorexic excitatory neurons
Authors: van den Pol Anthony N. , Acuna Claudio , Davis John N. , Huang Hao , Zhang Xiaobing
Published: January 2019

Key points

Excitatory glutamate neurons are sparse in the rostral hypothalamic arcuate nucleus (ARC), the subregion that has received the most attention in the past. In striking contrast, excitatory neurons are far more common (by a factor of 10) in the caudal ARC, an area which has received relatively little attention.

These glutamate cells may play a negative role in energy balance and food intake. They can show an increase in phosphorylated Stat‐3 in the presence of leptin, are electrically excited by the anorectic neuromodulator cholecystokinin, and inhibited by orexigenic neuromodulators neuropeptide Y, met‐enkephalin, dynorphin and the catecholamine dopamine.

The neurons project local axonal connections that excite other ARC neurons including proopiomelanocortin neurons that can play an important role in obesity.

These data are consistent with models suggesting that the ARC glutamatergic neurons may play both a rapid and a slower role in acting as anorectic neurons in CNS control of food intake and energy homeostasis.

Here we interrogate a unique class of excitatory neurons in the hypothalamic arcuate nucleus (ARC) that utilizes glutamate as a fast neurotransmitter using mice expressing GFP under control of the vesicular glutamate transporter 2 (vGluT2) promoter. These neurons show a unique distribution, synaptic characterization, cellular physiology and response to neuropeptides involved in energy homeostasis. Although apparently not previously appreciated, the caudal ARC showed a far greater density of vGluT2 cells than the rostral ARC, as seen in transgenic vGluT2‐GFP mice and mRNA analysis. After food deprivation, leptin induced an increase in phosphorylated Stat‐3 in vGluT2‐positive neurons, indicating a response to hormonal cues of energy state. Based on whole‐cell recording electrophysiology in brain slices, vGluT2 neurons were spontaneously active with a spike frequency around 2 Hz. vGluT2 cells were responsive to a number of neuropeptides related to energy homeostasis; they were excited by the anorectic peptide cholecystokinin, but inhibited by orexigenic neuropeptide Y, dynorphin and met‐enkephalin, consistent with an anorexic role in energy homeostasis. Dopamine, associated with the hedonic aspect of enhancing food intake, inhibited vGluT2 neurons. Optogenetic excitation of vGluT2 cells evoked EPSCs in neighbouring neurons, indicating local synaptic excitation of other ARC neurons. Microdrop excitation of ARC glutamate cells in brain slices rapidly increased excitatory synaptic activity in anorexigenic proopiomelanocortin neurons. Together these data support the perspective that vGluT2 cells may be more prevalent in the ARC than previously appreciated, and play predominantly an anorectic role in energy metabolism.
As Predictable as the Tides
Authors: Knapschaefer Johanna , Knapschaefer Johanna
Published: January 2019

The first live test is underway off Maine for a new technology that relies on strong tides and currents to power underwater generators. It took innovative engineering and precision execution to make the first test happen, but it could open the door to a new renewable energy source. In Europe, South American and Japan, which have expensive grid power costs, tidal energy is expected to become competitive. This article delves deeper into the engineering behind underwater turbines.
Definition and Interpretation of Wind Farm Efficiency in Complex Terrain: A Discussion
Authors: Astolfi Davide , Castellani Francesco , Terzi Ludovico
Published: January 2019

The exploitation of wind turbines in complex terrain has recently been growing. The comprehension of wind flow, especially in the downstream area, is by itself a challenging task in complex terrain: even more so, it is difficult to account for the mixing between terrain effects and the wake interactions between nearby turbines. Efficiency is one of the simplest and meaningful metrics for quantifying the impact of wakes on wind farm production, but its definition is well established basically only for offshore wind farms. In this work, the definition of wind farm efficiency is, therefore, discussed, based on the critical points arising in complex terrain, where there can be at the same time a considerable variation of free wind flow along the layout and a directional distortion of the wakes, induced by the terrain. In this work, operational data of a test case wind farm sited in a very complex terrain, featuring 17 multimegawatt wind turbines, are elaborated and inspire a discussion and a novel definition of efficiency, that restores in the complex terrain case the meaning of the efficiency.
Diminution of Useful Solar Gains by Capacitive Thermal Losses and Thermal Piping Losses in a Solar Process Heat Plant With Parabolic Trough Collectors in Switzerland
Authors: Möllenkamp Jana , Rittmann-Frank Mercedes H. , Häberle Andreas , Beikircher Thomas , Schölkopf Wolfgang
Published: January 2019

Process heat represents a major share of final energy consumption in the industrial sector and can partly be provided by solar thermal systems. To date, there has been little experience with solar heat plants for industrial processes operating at medium temperature levels (100–250 °C). This paper focuses on the analysis of reduced solar gains by heating-up processes (capacitive thermal losses) in a parabolic trough collector field with an aperture area of 627 m2 providing solar heat for a Swiss dairy at 120 °C. Heating-up thermal masses is experimentally quantified by a new method using existing temperature sensors. The unused solar thermal gains of heating-up periods amount to 18% of possible useful solar gains in 2014. In winter months, this share can reach 50%. Preserving the hot fluid content in an ideally insulated storage in the evening could avoid heating-up in the morning and reduce capacitive thermal losses by 38%. With properly installed insulation thermal losses of the piping system during operation are theoretically proven to be below 3% of useful solar gains. The analyses are based on the evaluation of highly time-resolved measurements of one year.
LIPID MAPS: Serving the next generation of lipid researchers with tools, resources, data, and training
Authors: O’Donnell Valerie B. , Dennis Edward A. , Wakelam Michael J. O. , Subramaniam Shankar
Published: January 2019

LIPID MAPS is a free resource dedicated to serving the lipid research community.
Draft Genome Sequence of KCTC 12630, the Type Strain of the Novel Species Sphingomonas ginsengisoli
Authors: Li Yan-Qiong , Zhang Hui , Narsing Rao Manik Prabhu , Dong Zhou-Yan , Alkhalifah Dalal Hussien M. , Hozzein Wael N. , Xiao Min , Li Wen-Jun
Published: January 2019

We report here the draft genome sequence of
Sphingomonas ginsengisoli
KCTC 12630
T
. The draft genome has a size of 3,045,889 bp and a G+C content of 67.1%.
Complete Genome Sequence of
Pseudomonas
sp. Strain phDV1, an Isolate Capable of Efficient Degradation of Aromatic Hydrocarbons
Authors: Xie Hao , Valsamidis Giannis , Mathioudaki Eirini , Tsiotis Georgios
Published: January 2019

Pseudomonas
sp. strain phDV1 is a Gram-negative bacterium capable of degrading aromatic hydrocarbons. Here, we present the complete genome sequence of this strain, which consists of 4,727,682 bp, with a 62.3% G+C content and 4,574 genes.
Genome Sequences of Livestock-Associated Methicillin-Resistant Staphylococcus aureus
spa
Type t899 Strains Belonging to Three Different Sequence Types (ST398, ST9, and ST4034)
Authors: Tegegne Henok Ayalew , Koláčková Ivana , Florianová Martina , Gelbíčová Tereza , Wattiau Pierre , Boland Cécile , Karpíšková Renáta
Published: January 2019

Livestock-associated methicillin-resistant
Staphylococcus aureus
(LA-MRSA) is an emerging MRSA lineage rapidly evolving in the community. In this report, we present the draft genome sequences of nine LA-MRSA strains.
Draft Genome Sequence of
Micromonospora
sp. Strain MW-13, a Bacterial Strain with Antibacterial Properties and Plant Growth Promotion Potential Isolated from the Rhizosphere of Wheat in Iran
Authors: Jahanshah Ghazaleh , Miess Henrike , Busche Tobias , Rückert Christian , Kalinowski Jörn , Rokni-Zadeh Hassan , Gross Harald
Published: January 2019

Strain MW13 exhibited broad-spectrum antibacterial activity toward Gram-positive and Gram-negative pathogens. The 7.1-Mb draft genome gives insight into the complete secondary metabolite production capacity and reveals genes putatively responsible for its antibacterial activity, as well as genes which contribute to plant growth promotion.
Metagenomic Analysis of Samples from Three Bat Species Collected in the Amazon Rain Forest
Authors: Franco Filho Luciano Chaves , Barata Rafael Ribeiro , Cardoso Jedson Ferreira , Massafra Janaina Mota de Vasconcelos , Lemos Poliana da Silva , Casseb Livia Medeiros Neves , Cruz Ana Cecilia Ribeiro , Nunes Marcio Roberto Teixeira
Published: January 2019

We report here the sequencing of five microbiome samples collected from different bat species in the Amazon rain forest. All contigs matching virus sequences were assigned to members of the
Retroviridae
family, while the bacterial contigs matched several bacterial species mostly belonging to the
Proteobacteria
phylum.
Genome Sequence of
Arenibacter algicola
Strain SMS7, Found in Association with the Marine Diatom
Skeletonema marinoi
Authors: Töpel Mats , Pinder Matthew I. M. , Johansson Oskar N. , Kourtchenko Olga , Godhe Anna , Clarke Adrian K.
Published: January 2019

Arenibacter algicola
strain SMS7 was isolated from a culture of the marine diatom
Skeletonema marinoi
strain ST54, sampled from top-layer sediments in Kosterfjord, Sweden. Here, we present its 5,857,781-bp genome, consisting of a circular chromosome and one circular plasmid, in all containing 4,932 coding sequences.
Sepsis associated acute kidney injury
Authors: Poston Jason T , Koyner Jay L
Published: January 2019

Sepsis is defined as organ dysfunction resulting from the host’s deleterious response to infection. One of the most common organs affected is the kidneys, resulting in sepsis associated acute kidney injury (SA-AKI) that contributes to the morbidity and mortality of sepsis. A growing body of knowledge has illuminated the clinical risk factors, pathobiology, response to treatment, and elements of renal recovery that have advanced our ability to prevent, detect, and treat SA-AKI. Despite these advances, SA-AKI remains an important concern and clinical burden, and further study is needed to reduce the acute and chronic consequences. This review summarizes the relevant evidence, with a focus on the risk factors, early recognition and diagnosis, treatment, and long term consequences of SA-AKI. In addition to literature pertaining to SA-AKI specifically, pertinent sepsis and acute kidney injury literature relevant to SA-AKI was included.
Quantum time delay for unitary operators: General theory
Authors: Sambou D. , Tiedra de Aldecoa R.
Published: January 2019

We present a suitable framework for the definition of quantum time delay in terms of sojourn times for unitary operators in a two-Hilbert spaces setting. We prove that this time delay defined in terms of sojourn times (time-dependent definition) exists and coincides with the expectation value of a unitary analogue of the Eisenbud–Wigner time delay operator (time-independent definition). Our proofs rely on a new summation formula relating localization operators to time operators and on various tools from functional analysis such as Mackey’s imprimitivity theorem, Trotter–Kato formula and commutator methods for unitary operators. Our approach is general and model-independent.
Alternative Diagnosis of Epilepsy in Children Without Epileptiform Discharges Using Deep Convolutional Neural Networks
Authors: Lin Lung-Chang , Ouyang Chen-Sen , Wu Rong-Ching , Yang Rei-Cheng , Chiang Ching-Tai
Published: January 2019

Numerous nonepileptic paroxysmal events, such as syncope and psychogenic nonepileptic seizures, may imitate seizures and impede diagnosis. Misdiagnosis can lead to mistreatment, affecting patients’ lives considerably. Electroencephalography is commonly used for diagnosing epilepsy. Although on electroencephalograms (EEGs), epileptiform discharges (ED) specifically indicate epilepsy, only approximately 50% of patients with epilepsy have ED in their first EEG. In this study, we developed a deep convolutional neural network (ConvNet)-based classifier to distinguish EEG between patients with epilepsy without ED and controls. Overall, 25 patients with epilepsy without ED in their EEGs and 25 age-matched patients with Tourette syndrome or syncope were enrolled. Their EEGs were classified using the deep ConvNet. When the EEG data without overlapping were used, the accuracy, sensitivity, and specificity were 65.00%, 48.00%, and 82.00%, respectively. The performance measures improved when the input EEG data were augmented through overlapping. With 95% EEG data overlapping, the accuracy, sensitivity, and specificity increased to 80.00%, 70.00%, and 90.00%, respectively. The proposed method could be regarded as a pilot study to demonstrate a proof of concept of a potential diagnostic value of deep ConvNet in patients with epilepsy without ED. Further studies are needed to assist neurologists in distinguishing nonepileptic paroxysmal events from epilepsy.
Group actions on quiver varieties and applications
Authors: Hoskins Victoria , Schaffhauser Florent
Published: January 2019

We study algebraic actions of finite groups of quiver automorphisms on moduli spaces of quiver representations. We decompose the fixed loci using group cohomology and we give a modular interpretation of each component. As an application, we construct branes in hyperkähler quiver varieties, as fixed loci of such actions.
HOW DIFFERENT HOMOPHILY PREFERENCES MITIGATE AND SPUR ETHNIC AND VALUE SEGREGATION: SCHELLING’S MODEL EXTENDED
Authors: PAOLILLO ROCCO , LORENZ JAN
Published: January 2019

In Schelling’s segregation model, agents of two ethnic groups reside in a regular grid and aim to live in a neighborhood that matches the minimum desired fraction of members of the same ethnicity. The model shows that observed segregation can emerge from people interacting under spatial constraints following homophily preferences. Even mild preferences can generate high degrees of segregation at the macro level. In modern, ethnically diverse societies, people might not define similarity based on ethnicity. Instead, shared tolerance towards ethnic diversity might play a more significant role, impacting segregation and integration in societies. With this consideration, we extend Schelling’s model by dividing the population of agents into value-oriented and ethnicity-oriented agents. Using parameter sweeping, we explore the consequences that the mutual adaptation of these two types of agents has on ethnic segregation, value segregation, and population density in the neighborhood. We examine for equally sized ethnic groups and for majority–minority conditions. The introduction of value-oriented agents reduces total ethnic segregation compared to Schelling’s original model, but the new value segregation appears to be more pronounced than ethnic segregation. Due to spillover effects, stronger ethnic homophily preferences lead not only to greater ethnic segregation, but also to more value segregation. Stronger value-orientation of the tolerant agents similarly leads to increased ethnic segregation of the ethnicity-oriented agents. Also, value-oriented agents tend to live in neighborhoods with more agents than ethnicity-oriented agents. In majority–minority settings, such effects appear to be more drastic for the minority than the majority ethnicity.
On the corpuscular theory of gravity
Authors: Giusti Andrea
Published: January 2019

The aim of this work is to provide a general description of the corpuscular theory of gravity. After reviewing some of the major conceptual issues emerging from the semiclassical and field theoretic approaches to Einstein’s gravity, we present a synthetic overview of two novel (and extremely intertwined) perspectives on quantum mechanical effects in gravity: the horizon quantum mechanics (HQM) formalism and the classicalization scheme. After this preliminary discussion, we then proceed with implementing the latter to several different scenarios, namely self-gravitating systems, the early Universe, and galactic dynamics. Concerning the first scenario, we start by describing the generation of the Newtonian potential as the result of a coherent state of toy (scalar) gravitons. After that we employ this result to study some features of the gravitational collapse and to argue that black holes can be thought of a self-sustained quantum states, at the critical point, made of a large number of soft virtual gravitons. We then refine this simplified analysis by constructing an effective theory for the gravitational potential of a static spherical symmetric system up to the first post-Newtonian correction. Additionally, we employ the HQM formalism to study the causal structure emerging from the corpuscular scenario. Finally, we present a short discussion of corpuscular black holes in lower dimensional spaces. After laying down the basics of corpuscular black holes, we present a generalization of the aforementioned arguments to cosmology. Specifically, we first introduce a corpuscular interpretation of the de Sitter spacetime. Then we use it as the starting point for a corpuscular formulation of the inflationary scenario and to provide an alternative viewpoint on the dark components of the [Formula: see text]CDM model. The key message of this work is that the corpuscular theory of gravity offers a way to unify most of the experimental observations (from astrophysical to galactic and cosmological scales) in a single framework, solely based on gravity and baryonic matter.
Robust Spectral Ensemble Clustering via Rank Minimization
Authors: Tao Zhiqiang , Liu Hongfu , Li Sheng , Ding Zhengming , Fu Yun
Published: January 2019

Ensemble Clustering (EC) is an important topic for data cluster analysis. It targets to integrate multiple Basic Partitions (BPs) of a particular dataset into a consensus partition. Among previous works, one promising and effective way is to transform EC as a graph partitioning problem on the co-association matrix, which is a pair-wise similarity matrix summarized by all the BPs in essence. However, most existing EC methods directly utilize the co-association matrix, yet without considering various noises (e.g., the disagreement between different BPs and the outliers) that may exist in it. These noises can impair the cluster structure of a co-association matrix, and thus mislead the final graph partitioning process. To address this challenge, we propose a novel Robust Spectral Ensemble Clustering (RSEC) algorithm in this article. Specifically, we learn low-rank representation (LRR) for the co-association matrix to uncover its cluster structure and handle the noises, and meanwhile, we perform spectral clustering with the learned representation to seek for a consensus partition. These two steps are jointly proceeded within a unified optimization framework. In particular, during the optimizing process, we leverage consensus partition to iteratively enhance the block-diagonal structure of LRR, in order to assist the graph partitioning. To solve RSEC, we first formulate it by using nuclear norm as a convex proxy to the rank function. Then, motivated by the recent advances in non-convex rank minimization, we further develop a non-convex model for RSEC and provide it a solution by the majorization--minimization Augmented Lagrange Multiplier algorithm. Experiments on 18 real-world datasets demonstrate the effectiveness of our algorithm compared with state-of-the-art methods. Moreover, several impact factors on the clustering performance of our approach are also explored extensively.
Fingolimod: Lessons Learned and New Opportunities for Treating Multiple Sclerosis and Other Disorders
Authors: Chun Jerold , Kihara Yasuyuki , Jonnalagadda Deepa , Blaho Victoria A.
Published: January 2019

Fingolimod (FTY720, Gilenya) was the first US Food and Drug Administration–approved oral therapy for relapsing forms of multiple sclerosis (MS). Research on modified fungal metabolites converged with basic science studies that had identified lysophospholipid (LP) sphingosine 1-phosphate (S1P) receptors, providing mechanistic insights on fingolimod while validating LP receptors as drug targets. Mechanism of action (MOA) studies identified receptor-mediated processes involving the immune system and the central nervous system (CNS). These dual actions represent a more general theme for S1P and likely other LP receptor modulators. Fingolimod's direct CNS activities likely contribute to its efficacy in MS, with particular relevance to treating progressive disease stages and forms that involve neurodegeneration. The evolving understanding of fingolimod's MOA has provided strategies for developing next-generation compounds with superior attributes, suggesting new ways to target S1P as well as other LP receptor modulators for novel therapeutics in the CNS and other organ systems.
Iron handling by the human kidney: glomerular filtration and tubular reabsorption both contribute to urinary iron excretion
Authors: van Raaij Sanne E. G. , Rennings Alexander J. , Biemond Bart J. , Schols Saskia E. M. , Wiegerinck Erwin T. G. , Roelofs Hennie M. J. , Hoorn Ewout J. , Walsh Stephen B. , Nijenhuis Tom , Swinkels Dorine W. , van Swelm Rachel P. L.
Published: January 2019

In physiological conditions, circulating iron can be filtered by the glomerulus and is almost completely reabsorbed by the tubular epithelium to prevent urinary iron wasting. Increased urinary iron concentrations have been associated with renal injury. However, it is not clear whether increased urinary iron concentrations in patients are the result of increased glomerular iron filtration and/or insufficient tubular iron reabsorption and if these processes contribute to renal injury. We measured plasma and urine iron parameters and urinary tubular injury markers in healthy human subjects ( n = 20), patients with systemic iron overload ( n = 20), and patients with renal tubular dysfunction ( n = 18). Urinary iron excretion parameters were increased in both patients with systemic iron overload and tubular dysfunction, whereas plasma iron parameters were only increased in patients with systemic iron overload. In patients with systemic iron overload, increased urinary iron levels were associated with elevated circulating iron, as indicated by transferrin saturation (TSAT), and increased body iron, as suggested by plasma ferritin concentrations. In patients with tubular dysfunction, enhanced urinary iron and transferrin excretion were associated with distal tubular injury as indicated by increased urinary glutathione S-transferase pi 1-1 (GSTP1-1) excretion. In systemic iron overload, elevated urinary iron and transferrin levels were associated with increased injury to proximal tubules, indicated by increased urinary kidney injury marker 1 (KIM-1) excretion. Our explorative study demonstrates that both glomerular filtration of elevated plasma iron levels and insufficient tubular iron reabsorption could increase urinary iron excretion and cause renal injury.
Computational Approach for Structural Feature Determination of Grapevine NHX Antiporters
Authors: Ayadi Mariem , Ben Ayed Rayda , Mzid Rim , Aifa Sami , Hanana Mohsen
Published: January 2019

Plant NHX antiporters are responsible for monovalent cation/H+ exchange across cellular membranes and play therefore a critical role for cellular pH regulation, Na+ and K+ homeostasis, and salt tolerance. Six members of grapevine NHX family (VvNHX1-6) have been structurally characterized. Phylogenetic analysis revealed their organization in two groups: VvNHX1-5 belonging to group I (vacuolar) and VvNHX6 belonging to group II (endosomal). Conserved domain analysis of these VvNHXs indicates the presence of different kinds of domains. Out of these, two domains function as monovalent cation-proton antiporters and one as the aspartate-alanine exchange; the remaining are not yet with defined function. Overall, VvNHXs proteins are typically made of 11-13 putative transmembrane regions at their N-terminus which contain the consensus amiloride-binding domain in the 3rd TM domain and a cation-binding site in between the 5th and 6th TM domain, followed by a hydrophilic C-terminus that is the target of several and diverse regulatory posttranslational modifications. Using a combination of primary structure analysis, secondary structure alignments, and the tertiary structural models, the VvNHXs revealed mainly 18 α helices although without β sheets. Homology modeling of the 3D structure showed that VvNHX antiporters are similar to the bacterial sodium proton antiporters MjNhaP1 (Methanocaldococcus jannaschii) and PaNhaP (Pyrococcus abyssi).
Fractal Analysis of the Long-Term Memory in Precipitation over Bénin (West Africa)
Authors: Agbazo Medard Noukpo , Koto N’Gobi Gabin , Alamou Eric , Kounouhewa Basile , Afouda Abel
Published: January 2019

This study analyzed the long-term memory (LTM) in precipitation over Bénin synoptic stations from 1951 to 2010 using the detrended fluctuation analysis (DFA) method. Results reveal the existence of positive long-term memory characteristic in rainfall field. DFA exponent values are different regarding the concerned synoptic stations, reflecting the effect of geographical position and climate on the LTM. These values were related to the type of climate. The best DFA1-4 method depends on the geographical position of the studied station. However, DFA2 is generally the best in terms of spatial average from DFA1 to DFA4. In Bénin synoptic stations, except the Parakou station, the long-term temporal correlations are systematically the source of multifractality in rainfall. Except Natitingou, the strength of long-term memory characteristic decreases each twenty years in the study period. Considering the fractal approach, our results show that the subperiod 1991–2010 is not really a transition period as shown before. Thus, the drought is prolonging until 2010. So, fractal theory reveals more Bénin climatic characteristics.
Chronic Lymphocytic Leukemia Presenting as a Subcortical Watershed Infarct
Authors: Gupta Mridul , Singh Divita , Lee Patrick , Kadiyam Sandhya
Published: January 2019

Internal watershed infarcts (WI) involve white matter between deep and superficial arterial systems of middle cerebral artery. These infarcts are considered to be either from low blood flow or microembolism. Anemia is an extremely rare cause of watershed infarcts. Very few cases of hemolytic anemia causing watershed cerebral infarcts have been reported. Chronic lymphocytic leukemia (CLL) is frequently complicated with secondary autoimmune cytopenia such as autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and pure red cell aplasia. AIHA is present in about 7–10% of patients with CLL. AIHA from CLL presenting as WI is an extremely rare phenomenon with no previously published case reports to the best of our knowledge.
High Glucose with Insulin Induces Cell Cycle Progression and Activation of Oncogenic Signaling of Bladder Epithelial Cells Cotreated with Metformin and Pioglitazone
Authors: Kim Daejin , Ahn Byul-Nim , Kim YeongSeok , Hur Dae Young , Yang Jae Wook , Park Ga Bin , Jang Jung Eun , Lee Eun Ju , Kwon Min Jeong , Kim Tae Nyun , Kim Mi Kyung , Park Jeong Hyun , Rhee Byoung Doo , Lee Soon Hee
Published: January 2019

Metformin and pioglitazone are two commonly prescribed oral hypoglycemic agents for diabetes. Recent evidence suggests that these drugs may contribute to bladder cancer. This study investigated molecular mechanism underlying effects of metformin and pioglitazone in bladder epithelial carcinogenesis in type 2 diabetes. The cells derived from human bladder epithelial cells (HBlEpCs) were treated with metformin or pioglitazone with high glucose and insulin. Cell viability and proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and a bromodeoxyuridine incorporation assay, respectively, while cell cycle regulatory factors and oncogene expression were analyzed using western blotting. Metformin or pioglitazone suppressed cell viability concentration and time dependently, which was reversed by exposure to high glucose with or without insulin. Prolonged exposure to high glucose and insulin enhanced cyclin D, cyclin-dependent kinase 4 (Cdk4), and Cdk2 expression and suppressed cyclin-dependent kinase inhibitors p21 and p15/16 in HBlEpC cotreated with pioglitazone and metformin. Levels of tumor suppressor proteins p53 and cav-1 were downregulated while those of the oncogenic protein as c-Myc were upregulated under high glucose and insulin supplementation in HBlEpC cotreated with pioglitazone and metformin. Prolonged exposure to high glucose with or without insulin downregulated B cell lymphoma 2-associated X (Bax) and failed to enhance the expression of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) in drug-treated cells. These results suggest that hyperglycemic and insulinemic conditions promote cell cycle progression and oncogenic signaling in drug-treated bladder epithelial cells and uncontrolled hyperglycemia and hyperinsulinemia are probably greater cancer risk factors than diabetes drugs.
Colchicine plus Dapsone in Colchicine‐Resistant FMF Patients
Authors: Salehzadeh Farhad , Enteshary A. , Moshkbar M.
Published: January 2019

Five to ten percent of FMF patients have unfavorable response to the colchicine as a standard therapy. Biologic treatments have been shown to be highly effective, but there are often unavailable, because the price is unaffordably high. This study shows the striking effect of combined dapsone and colchicine therapy in such patients and recommends it as an alternative therapy in colchicine-resistant (CR) patients.
In Silico Pelvis and Sacroiliac Joint Motion: Refining a Model of the Human Osteoligamentous Pelvis for Assessing Physiological Load Deformation Using an Inverted Validation Approach
Authors: Ramezani Maziar , Klima Stefan , de la Herverie Paul Le Clerc , Campo Jean , Le Joncour Jean-Baptiste , Rouquette Corentin , Scholze Mario , Hammer Niels
Published: January 2019

Introduction. Computational modeling of the human pelvis using the finite elements (FE) method has become increasingly important to understand the mechanisms of load distribution under both healthy and pathologically altered conditions and to develop and assess novel treatment strategies. The number of accurate and validated FE models is however small, and given models fail resembling the physiologic joint motion in particular of the sacroiliac joint. This study is aimed at using an inverted validation approach, using in vitro load deformation data to refine an existing FE model under the same mode of load application and to parametrically assess the influence of altered morphology and mechanical data on the kinematics of the model. Materials and Methods. An osteoligamentous FE model of the pelvis including the fifth lumbar vertebra was used, with highly accurate representations of ligament orientations. Material properties were altered parametrically for bone, cartilage, and ligaments, followed by changes in bone geometry (solid versus 3 and 2 mm shell) and material models (linear elastic, viscoelastic, and hyperelastic isotropic), and the effects of varying ligament fiber orientations were assessed. Results. Elastic modulus changes were more decisive in both linear elastic and viscoelastic bone, cartilage, and ligaments models, especially if shell geometries were used for the pelvic bones. Viscoelastic material properties gave more realistic results. Surprisingly little change was observed as a consequence of altering SIJ ligament orientations. Validation with in vitro experiments using cadavers showed close correlations for movements especially for 3 mm shell viscoelastic model. Discussion. This study has used an inverted validation approach to refine an existing FE model, to give realistic and accurate load deformation data of the osteoligamentous pelvis and showed which variation in the outcomes of the models are attributed to altered material properties and models. The given approach furthermore shows the value of accurate validation and of using the validation data to fine tune FE models.
Evaluation of Dual-Cure Resin Cement Polymerization under Different Types and Thicknesses of Monolithic Zirconia
Authors: Turkoglu Pinar , Sen Deniz
Published: January 2019

Purpose. The aim of the present study was to investigate the effects of the type and thickness of the zirconia material on the microhardness of the underlying dual-cure resin cement. Materials and Methods. Eight disk-shaped zirconia specimens with a 4-mm diameter and four varying thicknesses (0.5, 1.0, 1.5, and 2.0 mm) were fabricated from two different monolithic zirconia materials: posterior monolithic zirconia (Prettau) and anterior monolithic zirconia (Prettau Anterior). Dual-cure resin cement specimens with a 4-mm diameter and 5-mm height were prepared using Teflon cylinder molds and activated by light beneath the eight zirconia disks and without any zirconia disk for 20 s (n=12). A total of 108 specimens were embedded in acrylic. Vickers hardness of each specimen was measured at three different depths using a microhardness device with a 50-g load. All data were statistically evaluated using three-way ANOVA, one-way ANOVA, independent samples t-tests, and Bonferroni corrected post hoc tests (α=.05). Results. Dual-cure resin cement’s microhardness was significantly higher for the samples polymerized beneath anterior monolithic zirconia compared to posterior monolithic zirconia. The hardness decreased as the thickness increased for both types of zirconia; the latter was attributed to an attenuated curing efficiency. Conclusion. Microhardness of the dual-cure resin cement is influenced by both the type and the thickness of the monolithic zirconia restoration. Polymerization efficiency for resin cement cured under anterior monolithic zirconia may be superior to cured beneath posterior monolithic zirconia.
A Case of Violent Suicide Attempt in a Context of Myxedema Psychosis following Radioiodine Treatment in a Patient with Graves’ Disease
Authors: Todorov Louise , Ait Boudaoud Amel , Pascal de Raykeer Rachel , Radu Alina , Lahlou-Laforêt Khadija , Limosin Frédéric , Lemogne Cédric , Czernichow Sébastien
Published: January 2019

Introduction. Hypothyroidism has been associated with mood disorders but some cases of acute psychosis have also been reported. However, less attention has been paid to suicidal behavior in these patients. Case Report. We report a case of suicide attempt by self-stabbing in a 43-year-old woman without past psychiatric history, four months after radioiodine therapy for Graves’ disease. On clinical examination remarkable signs of myxedema were found and blood investigations showed hypothyroidism with an extremely high thyroid stimulating hormone (TSH) level (152 mUI/L; reference range 0.20-5.10). The patient presented delirium symptoms at the time of self-stabbing, which was associated with persecutory delusions and auditory harm command hallucinations. A rapid physical and psychiatric improvement was observed after the initiation of an oral thyroid replacement therapy without relapse after early discontinuation of the antipsychotic treatment. Discussion. The most distinctive feature of our case is that the violent suicide attempt could be attributed to the myxedema psychosis. Suicide may result from several factors, including psychosocial stressors, psychiatric symptoms, and hormonal disturbance. This unique presentation should remind clinicians to systematically consider ordering additional tests in patients with atypical psychiatric presentation, even when serious behavioral disorders (such as violent suicide attempts) are present and may result in premature transfer to psychiatric units.
Hypoxia-Activated PI3K/Akt Inhibits Oxidative Stress via the Regulation of Reactive Oxygen Species in Human Dental Pulp Cells
Authors: Liu Fei , Huang Xin , Luo Zhenhua , He Jingjun , Haider Farhan , Song Ci , Peng Ling , Chen Ting , Wu Buling
Published: January 2019

In order to use stem cells as a resource for tissue regeneration, it is necessary to induce expansion in vitro. However, during culture, stem cells often lose functional properties and become senescent. Increasing evidence indicates that hypoxic preconditioning with physiological oxygen concentration can maintain the functional properties of stem cells in vitro. The purpose of the current study was to test the hypothesis that hypoxic preconditioning with physiological oxygen concentration can maintain the functional properties of stem cells in culture by reducing oxidative stress. In vitro studies were performed in primary human dental pulp cells (hDPCs). Reduced levels of oxidative stress and increased cellular “stemness” in response to physiological hypoxia were dependent upon the expression of reactive oxygen species (ROS). Subsequently, RNA-sequencing analysis revealed the increased expression of phosphoinositide 3-kinase (PI3K)/Akt signaling in culture, a pathway which regulates oxidative stress. Furthermore, we found evidence that PI3K/Akt signaling might affect intracellular ROS production by negatively regulating expression of the downstream protein Forkhead Box Protein O1 (FOXO1) and Caspase 3. Collectively, our data show that the PI3K/Akt pathway is activated in response to hypoxia and inhibits oxidative stress in a ROS-dependent manner. This study identified redox-mediated hypoxic preconditioning regulatory mechanisms that may be significant for tissue regeneration.
β-Fructofuranosidase andβ–D-Fructosyltransferase from NewAspergillus carbonariusPC-4 Strain Isolated from Canned Peach Syrup: Effect of Carbon and Nitrogen Sources on Enzyme Production
Authors: Nascimento Gustavo Carvalho do , Batista Ryhára Dias , Santos Claudia Cristina Auler do Amaral , Silva Ezequiel Marcelino da , de Paula Fabrício Coutinho , Mendes Danylo Bezerra , de Oliveira Deyla Paula , Almeida Alex Fernando de
Published: January 2019

β-fructofuranosidase (invertase) andβ-D-fructosyltransferase (FTase) are enzymes used in industrial processes to hydrolyze sucrose aiming to produce inverted sugar syrup or fructooligosaccharides. In this work, a blackAspergillussp. PC-4 was selected among six filamentous fungi isolated from canned peach syrup which were initially screened for invertase production. Cultivations with pure carbon sources showed that invertase and FTase were produced from glucose and sucrose, but high levels were also obtained from raffinose and inulin. Pineapple crown was the best complex carbon source for invertase (6.71 U/mL after 3 days of cultivation) and FTase production (14.60 U/mL after 5 days of cultivation). Yeast extract and ammonium chloride nitrogen sources provided higher production of invertase (6.80 U/mL and 6.30 U/mL, respectively), whereas ammonium nitrate and soybean protein were the best nitrogen sources for FTase production (24.00 U/mL and 24.90 U/mL, respectively). Fermentation parameters for invertase using yeast extract wereYP/S= 536.85 U/g andPP= 1.49 U/g/h. FTase production showed values ofYP/S= 2,627.93 U/g andPP= 4.4 U/h using soybean protein. The screening for best culture conditions showed an increase of invertase production values by 5.10-fold after 96 h cultivation compared to initial experiments (fungi bioprospection), while FTase production increased by 14.60-fold (44.40 U/mL) after 168 h cultivation.A. carbonariusPC-4 is a new promising strain for invertase and FTase production from low cost carbon sources, whose synthesized enzymes are suitable for the production of inverted sugar, fructose syrups, and fructooligosaccharides.
Preparation of a Nitrogen-Doped Reduced Graphene Oxide-Modified Graphite Felt Electrode for VO2+/VO2+ Reaction by Freeze-Drying and Pyrolysis Method
Authors: Li Qiang , Liu Jiaqiang , Bai Anyu , Li Penghui , Li Jie , Zhang Xiaochen , Yu Mingfu , Wang Junhai , Sun Hong
Published: January 2019

As one of the key factors that limit the development of vanadium redox flow battery (VRFB), the positive redox couple of VO2+/VO2+ plays an important role on the overall performance of VRFB. To improve the kinetics of a positive reaction, a new designed nitrogen-doped reduced graphene oxide-modified graphite felt (N-rGO/GF) electrode was prepared by coupling the methods of freeze-drying and pyrolysis. The characteristics of the prepared electrode were measured by scanning electron microscope (SEM), Brunauer–Emmett–Teller (BET) analysis, Raman spectroscopy (Raman), X-ray diffraction (XRD), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and charge-discharge tests. By coupling the methods of freeze-drying and pyrolysis, the N-rGO can be evenly dispersed on the surface of GF electrode, resulting in an excellent catalytic activity. The results demonstrate that the proposed N-rGO/GF electrode with pyrolysis temperature of 900°C shows excellent electrochemical performance and significantly improves the catalytic activity and electrochemical reversibility for the positive VO2+/VO2+ reaction, indicating that the proposed composite electrode has potential applications in the improvement of VRFB performance.
Permeability Estimation Based on the Geometry of Pore Space via Random Walk on Grids
Authors: Nan Tongchao , Wu Jichun , Li Kaixuan , Jiang Jianguo
Published: January 2019

In the literature, the mean penetration depth (MPD) calculated by “walk on spheres” or “walk on cubes” was used to quickly estimate the intrinsic permeability of digitized porous media. However, these two methods encounter difficulties such as irregular boundaries and the determination of arrivals at a boundary. In this study, an MPD method that is based on a more flexible “random walk on grid” (WOG) is explored. Moreover, the accurate MPDs for the pores of simple shapes are derived with Green’s functions to validate the WOG-based MPD. The results suggested that MPDs based on Green’s functions and WOG are consistent with each other; the factor C in the permeability expression is slightly dependent on roundness of the cross sections and is approximately 1.125 on average, according to analytical and numerical results. In a synthetic complex pore, the permeability estimated by WOG is comparable to, but greater than, the estimate based on the pore-scale dynamics simulation in COMSOL.
Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis
Authors: Carrer Alessandro , Trefely Sophie , Zhao Steven , Campbell Sydney L. , Norgard Robert J. , Schultz Kollin C. , Sidoli Simone , Parris Joshua L.D. , Affronti Hayley C. , Sivanand Sharanya , Egolf Shaun , Sela Yogev , Trizzino Marco , Gardini Alessandro , Garcia Benjamin A. , Snyder Nathaniel W. , Stanger Ben Z. , Wellen Kathryn E.
Published: January 2019

Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abundance regulates global histone acetylation, we hypothesized that altered acetyl-CoA metabolism might contribute to metabolic or epigenetic alterations that promote tumorigenesis. We found that acetyl-CoA abundance is elevated in KRAS-mutant acinar cells and that its use in the mevalonate pathway supports acinar-to-ductal metaplasia (ADM). Pancreas-specific loss of the acetyl-CoA–producing enzyme ATP-citrate lyase (ACLY) accordingly suppresses ADM and tumor formation. In PDA cells, growth factors promote AKT–ACLY signaling and histone acetylation, and both cell proliferation and tumor growth can be suppressed by concurrent BET inhibition and statin treatment. Thus, KRAS-driven metabolic alterations promote acinar cell plasticity and tumor development, and targeting acetyl-CoA–dependent processes exerts anticancer effects.

Significance:

Pancreatic cancer is among the deadliest of human malignancies. We identify a key role for the metabolic enzyme ACLY, which produces acetyl-CoA, in pancreatic carcinogenesis. The data suggest that acetyl-CoA use for histone acetylation and in the mevalonate pathway facilitates cell plasticity and proliferation, suggesting potential to target these pathways.

See related commentary by Halbrook et al., p. 326.

This article is highlighted in the In This Issue feature, p. 305
Circulating Tumor Cells: Come Together, Right Now, Over Metastasis
Authors: Rodrigues Paulo , Vanharanta Sakari
Published: January 2019

Circulating tumor cells (CTC) are the source of metastases, but only an infinitesimal fraction of them eventually succeed in colonizing a distant organ. New results show that CD44-dependent aggregation in the circulation provides CTCs with cancer stem cell–like characteristics, suggesting an explanation for the low metastatic efficiency of CTCs, but also avenues for therapeutic intervention.

See related article by Liu et al., p. 96.
Evading the STING: LKB1 Loss Leads to STING Silencing and Immune Escape in KRAS-Mutant Lung Cancers
Authors: Della Corte Carminia Maria , Byers Lauren Averett
Published: January 2019

Mutations in STK11 (LKB1) are a major cause of primary resistance to immunotherapy in non–small cell lung cancer. Kitajima and colleagues dissect the underlying mechanism of this immune-resistant phenotype, demonstrating that LKB1 loss leads directly to suppression of stimulator of interferon genes (STING) and insensitivity to cytoplasmic double-strand DNA detection. Therapies that reactivate LKB1 or theSTING pathway may boost anticancer immune response in cancers with resistance to immune-checkpoint blockade.

See related article by Kitajima et al., p. 34.
Something Old, Something New: The Tumor Microenvironment Comes of Age
Authors: Marie Kerrie L. , Merlino Glenn
Published: January 2019

In this issue, Weeraratna and colleagues demonstrate that observed differences in melanoma aggressiveness in younger versus older patients can be explained not just by cell-intrinsic alterations over time, but by age-dependent changes in fibroblasts and the extracellular matrix they help create. Their findings identify novel cellular targets for melanoma therapy, as well as candidate prognostic biomarkers to better inform clinical decisions for patients with melanoma.

See related article by Kaur et al., p. 64.

See related article by Ecker et al., p. 82.