bluuebunny/crossref_metadata_2025 huggingface dataset:
The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate‐precuneus pathway
Authors: Huang Wei , King Jean A. , Ursprung W. W. Sanouri , Zheng Shaokuan , Zhang Nanyin , Kennedy David N. , Ziedonis Douglas , DiFranza Joseph R.
Published: March 2014

Introduction

Perturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus.

Methods

Using functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting‐state functional connectivity analysis using the anterior cingulate cortex as a seed.

Results

Independent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed‐based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal‐induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60–0.76; P < 0.05).

Conclusions

In concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting‐state functional connectivity in this pathway increases during nicotine withdrawal in correlation with the intensity of withdrawal‐induced craving. These findings suggest that smoking triggers structural and functional neural adaptations in the brain that support withdrawal‐induced craving.
Decreased decorin expression in the tumor microenvironment
Authors: Bozoky Benedek , Savchenko Andrii , Guven Hayrettin , Ponten Fredrik , Klein George , Szekely Laszlo
Published: March 2014

Decorin is a small leucine‐rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor.
A rare case report: SCARF syndrome
Authors: Rahimpour Masoume , Sohrabi Mohammad bager , Kalhor Sulmaz , Khosravi Hossein ali , Zolfaghari Poone , Yahyaei Elahe
Published: March 2014

Key Clinical Message

SCARF syndrome is a very rare syndrome that so far only two cases have been reported in the papers. In this article, a 3‐month‐old female who exhibited SCARF syndrome presented with multiple congenital abnormalities and problems at Imam Hossein hospital of Shahroud.
Treatment and survival in 10,429 patients with localized laryngeal cancer: A population‐based analysis
Authors: Misono Stephanie , Marmor Schelomo , Yueh Bevan , Virnig Beth A.
Published: March 2014

BACKGROUND

The objectives of this study were to identify factors associated with treatment differences, characterize changes in treatment patterns over time, and compare survival across treatment types in patients who received treatment for localized laryngeal cancer.

METHODS

Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of patients who were treated from 1995 to 2009 for localized laryngeal cancer. Four treatment groups were defined: (1) radiation only, (2) local surgery only, (3) local surgery and radiation, and (4) open surgery with or without radiation. Variations in treatment rates between these groups were evaluated according to demographic factors, and differences in treatment rates across time were calculated. Associations between treatment and mortality were assessed using Kaplan‐Meier methods. Cox proportional hazards regression models were used to adjust for potential confounding covariates.

RESULTS

In total, 10,429 patients with localized laryngeal cancer were identified. Most patients (57%) were treated with radiation only; 25% with local surgery and radiation, 9% with local surgery only, and 9% with open surgery with or without radiation. Race, age, and registry were associated with differences in treatment. Receipt of single‐modality treatment increased and receipt of combined‐modality treatment decreased over the study period. Better survival was observed with white race, younger age, and treatment with local surgery. Survival differences associated with treatment type were observed within 3 years of diagnosis and persisted beyond 5 years after diagnosis.

CONCLUSIONS

Although treatment patterns became more adherent to treatment guidelines over time, we identified survival differences associated with treatment type that warrant further investigation into treatment decision‐making for patients with localized laryngeal cancer. Cancer 2014;120:1810–1817. © 2014 American Cancer Society.
Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes
Authors: Ferrer Darío G. , Jaldín‐Fincati Javier R. , Amigone José L. , Capra Raul H. , Collino César J. , Albertini Ricardo A. , Chiabrando Gustavo A.
Published: March 2014

In this article, we present a flow cytometry assay by which human blood monocyte subpopulations—classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes—can be determined. Monocytic cells were selected from CD45+ leukocyte subsets by differential staining of the low‐density lipoprotein receptor‐related protein 1 (LRP1), which allows reducing the spill‐over of natural killer cells and granulocytes into the CD16+ monocyte gate. Percentages of monocyte subpopulations established by this procedure were significantly comparable with those obtained by a well‐standardized flow cytometry assay based on the HLA‐DR monocyte‐gating strategy. We also demonstrated that LRP1 is differentially expressed at cell surface of monocyte subpopulations, being significantly lower in nonclassical monocytes than in classical and intermediate monocytes. Cell surface expression of LRP1 accounts for only 20% of the total cellular content in each monocyte subpopulation. Finally, we established the within‐individual biological variation (bCV%) of circulating monocyte subpopulations in healthy donors, obtaining values of 21%, 20%, and 17% for nonclassical, intermediate, and classical monocytes, respectively. Similar values of bCV% for LRP1 measured in each monocyte subpopulation were also obtained, suggesting that its variability is mainly influenced by the intrinsic biological variation of circulating monocytes. Thus, we conclude that LRP1 can be used as a third pan‐monocytic marker together with CD14 and CD16 to properly identify monocyte subpopulations. The combined determination of monocyte subpopulations and LRP1 monocytic expression may be relevant for clinical studies of inflammatory processes, with special interest in atherosclerosis and cardiovascular disease. © 2014 International Society for Advancement of Cytometry
Distributed topology management for wireless multimedia sensor networks: exploiting connectivity and cooperation
Authors: Misra Sudip , Mali Goutam , Mondal Ayan
Published: March 2014

In this paper, we propose a distributed topology management algorithm, named T‐Must, which orchestrates coalition formation game between camera and scalar sensor (SS) nodes, for use in wireless multimedia sensor networks. In the proposed solution, connectivity among the peer camera sensor (CS) nodes is maintained, and coverage is ensured between them. Only the scalar data are not sufficient to describe an event in a particular monitored area. In many cases, multimedia data (specifically, video data) are required to provide more precise information about the event. As the CS nodes, which sense and transmit multimedia data, are costlier than the SS nodes, the former are deployed in the monitored area in lesser numbers compared to the latter ones. In case of CS nodes, power consumption due to sensing is also significant, similar to power consumption for the transmission and reception of packets. Therefore, in this work, in order to increase the network lifetime, topology is controlled by forming coalition between the CS and SS nodes. Upon occurrence of an event, the SS nodes send scalar data to their associated CS nodes. If the scalar data received from SS nodes cross a preconfigured threshold, the associated CS node in the coalition starts sensing the event, captures the video data, and forwards the video data toward other coalitions or sink. Copyright © 2014 John Wiley & Sons, Ltd.
Postbrushing and fine‐needle aspiration biopsy follow‐up and treatment options for patients with pancreatobiliary lesions: The papanicolaou society of cytopathology guidelines
Authors: Kurtycz Daniel , Tabatabai Z. Laura , Michaels Claire , Young Nancy , Schmidt C. Max , Farrell James , Gopal Deepak , Simeone Diane , Merchant Nipun B. , Field Andrew , Pitman Martha Bishop
Published: March 2014

The papanicolaou society of cytopathology (PSC) has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound (EUS) guided fine‐needle aspiration (FNA) biopsy, techniques of EUS‐FNA, terminology and nomenclature for pancreatobiliary cytology, ancillary testing, and postprocedure management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18 month period and synthesis of online comments of the draft document on the PSC web site [www.papsociety.org]. This document selectively presents the results of these discussions and focuses on the follow‐up and treatment options for patients after procedures performed for obtaining cytology samples for the evaluation of biliary strictures and solid and cystic masses in the pancreas. These recommendations follow the six‐tiered terminology and nomenclature scheme proposed by Committee III. Diagn. Cytopathol. 2014;42:363–371. © 2014 Wiley Periodicals, Inc.
Volumetric alterations in the nucleus accumbens and caudate nucleus in bulimia nervosa: A structural magnetic resonance imaging study
Authors: Coutinho Joana , Ramos Ana Filipa , Maia Liliana , Castro Liliana , Conceição Eva , Geliebter Allan , Machado Paulo P.P. , Gonçalves Óscar , Sampaio Adriana
Published: March 2014

Objective

Bulimia nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating and inappropriate compensatory behaviors (such as purging, fasting, or excessive exercise) to prevent weight gain. BN has been associated with deficits in inhibitory control processes. The basal ganglia specifically, the nucleus accumbens (NAc) and the caudate nucleus (CN) are part of the frontostriatal circuits involved in inhibitory control. The main goal of this study was to investigate the presence of morphological alterations in the NAc and the CN in a sample of patients diagnosed with BN.

Method

Forty‐one female participants, 21 diagnosed with BN and 20 healthy matched controls (HC), underwent a structural magnetic resonance imaging (MRI) acquisition and clinical assessment. The NAc and the CN were manually segmented using the software Slicer 3D.

Results

The results reveal a significant volumetric decrease in the CN and a preserved NAc volume in BN compared to the control group.

Discussion

These findings suggest a contributory role of the caudate nucleus part of the dorsal striatum in the psychopathology of BN. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:206–214)
Targeting myocardial remodelling to develop novel therapies for heart failure
Authors: Tarone Guido , Balligand Jean‐Luc , Bauersachs Johann , Clerk Angela , De Windt Leon , Heymans Stephane , Hilfiker‐Kleiner Denise , Hirsch Emilio , Iaccarino Guido , Knöll Ralph , Leite‐Moreira Adelino F. , Lourenço André P. , Mayr Manuel , Thum Thomas , Tocchetti Carlo G.
Published: March 2014

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta‐adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca2 + ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre‐clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.
Long‐term effectiveness of the combined minute ventilation and patient activity sensors as predictor of heart failure events in patients treated with cardiac resynchronization therapy: Results of the Clinical Evaluation of the Physiological Diagnosis Function in the PARADYM CRT device Trial (CLEPSYDRA) study
Authors: Auricchio Angelo , Gold Michael R. , Brugada Josep , Nölker G. , Arunasalam Siva , Leclercq Christophe , Defaye Pascal , Calò Leonardo , Baumann Oliver , Leyva Francisco
Published: March 2014

Aims

Monitoring early signs of clinical deterioration could allow physicians to adjust medical treatment for patients at risk of acute heart failure decompensation. To date, several strategies using different surrogate measures of clinical status emerged, but none has yet been proven to predict clinical events. We hypothesized that the Physiological Diagnostic feature, which combines data from minute ventilation and physical activity sensors, predicts heart failure events in patients implanted with cardiac resynchronization therapy with defibrillation (CRT‐D) devices.

Methods and results

The Clinical Evaluation of the Physiological Diagnostic feature in the PARADYM CRT device (CLEPSYDRA) trial is a multicentre, prospective, non‐randomized, double‐blind study comprising 521 CRT‐D patients with heart failure [67.4 ± 10.1 years (mean ± SD), 82% male, New York Heart Association class III/IV 85.0%/6.7%, QRS 155.3 ± 26.6 ms, left ventricular ejection fraction 25.7 ± 7.7%]. The objective of the study was the sensitivity and false positive rate of the Physiological Diagnostic algorithm to predict heart failure events within the following month. After a mean follow‐up of 17.0 ± 8.7 months, 130 (25.6%) patients experienced a heart failure event. The sensitivity of the algorithm to predict an event was 34% and the false positive rate was 2.4 per patient‐year.

Conclusion

Thirty‐four per cent of heart failure events occurring within a month were predicted by the Physiological Diagnostic algorithm, and 2.4 alerts per patient per year were not followed by an heart failure event within the subsequent month.
Photofunctional Conductors Based on TTF‐BODIPY Dyads Bearing p‐Phenylene and p‐Phenylenevinylene Spacers
Authors: Tsujimoto Keijiro , Ogasawara Reiko , Nakagawa Takahiro , Fujiwara Hideki
Published: March 2014

This paper describes the syntheses, crystal structure analyses and physical properties of new D–A dyads containing tetrathiafulvalene (TTF) and 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) moieties linked by a p‐phenylene or p‐phenylenevinylene spacer for the development of photoresponsive organic conducting materials that can show photofunctionality in the visible region. The absorption spectra of the synthesized dyads recorded in CHCl3 show strong absorptions at 505 nm originating from the BODIPY moiety and weak charge‐transfer absorptions at around 550 nm. The fluorescence corresponding to the BODIPY moiety was suppressed to less than half in all the dyads, which suggests the formation of photoinduced charge‐transfer states. All the thin‐film samples of the dyads spin‐coated onto ITO‐coated glass substrates exhibited electric current generation that are related to the absorption spectra of the thin films. In the crystalline samples of three dyads, the TTF moieties formed 1D conducting columns through the dimerization of the TTF moieties and relatively strong side‐by‐side interactions between neighbouring stacking columns. All the neutral crystals exhibited photoinduced conductivity along the stacking direction of the TTF moieties and the crystal with the weakest dimerization and the strongest side‐by‐side interaction showed the greatest photoconductivity of the three crystals. The PF6 salt of the dyad with a p‐phenylene spacer and a 2:1 stoichiometry of the dyad and anion exhibited semi‐conducting behaviour with a conductivity of 3.0 × 10–4 S cm–1 at room temperature and an activation energy of 0.18 eV, probably because this crystal has a half‐filled Mott insulating band structure that originates from strongly dimerized intermolecular interactions. Upon photoirradiation, this salt showed a slight enhancement of conductivity.
Evaluation of Large‐Scale Hydrogen Storage Systems in the German Energy Sector
Authors: Michaelis J. , Genoese F. , Wietschel M.
Published: March 2014

The increasing share of renewable energies in the German energy sector is changing the present generation structure and requires the usage of more flexible technologies. Storage systems are one option to balance fluctuating electricity generation and demand. But due to the high investments required, all storage technologies have difficulties meeting the challenge of economic feasibility. However, chemical long‐term storage technologies that use a gaseous medium as the energy carrier have the advantage of being a versatile storage medium that can be sold on different markets. This paper shows that serving both the electricity and fuel markets has positive impacts on the profitability of hydrogen storage systems. Under favorable conditions, which are characterized by high shares of renewable energies and high prices for energy carriers, a positive economic result is possible.
CD200R1 and CD200 expression are regulated by PPAR‐γ in activated glial cells
Authors: Dentesano Guido , Serratosa Joan , Tusell Josep M. , Ramón Pol , Valente Tony , Saura Josep , Solà Carme
Published: March 2014

The mechanisms that control microglial activation are of interest, since neuroinflammation, which involves reactive microglia, may be an additional target in the search for therapeutic strategies to treat neurodegenerative diseases. Neuron‐microglia interaction through contact‐dependent or independent mechanisms is involved in the regulation of the microglial phenotype in both physiological and pathological conditions. The interaction between CD200, which is mainly present in neurons but also in astrocytes, and CD200R1, which is mainly present in microglia, is one of the mechanisms involved in keeping the microglial proinflammatory phenotype under control in physiological conditions. Alterations in the expression of CD200 and CD200R1 have been described in neurodegenerative diseases, but little is known about the mechanism of regulation of these proteins under physiological or pathological conditions. The aim of this work was to study the modulation of CD200 and CD200R1 expression by peroxisome proliferator‐activated receptor gamma (PPAR‐γ), a transcription factor involved in the control of the inflammatory response. Mouse primary neuronal and glial cultures and neuron‐microglia cocultures were treated with the PPAR‐γ endogenous ligand 15‐deoxy‐Δ12, 14‐prostaglandin J2 (15d‐PGJ2) in the presence and absence of lipopolysaccharide plus interferon‐γ (LPS/IFN‐γ)‐induced glial activation. We show that 15d‐PGJ2 inhibits the pro‐inflammatory response and prevents both CD200R1 downregulation and CD200 upregulation in reactive glial cells. In addition, 15d‐PGJ2 abrogates reactive‐microglia induced neurotoxicity in neuron‐microglia cultures through a CD200‐CD200R1 dependent mechanism. These results suggest that PPAR‐γ modulates CD200 and CD200R1 gene expression and that CD200‐CD200R1 interaction is involved in the anti‐inflammatory and neuroprotective action of PPAR‐γ agonists. GLIA 2014;62:982–998
Brain systems mediating voice identity processing in blind humans
Authors: Hölig Cordula , Föcker Julia , Best Anna , Röder Brigitte , Büchel Christian
Published: March 2014

Blind people rely more on vocal cues when they recognize a person's identity than sighted people. Indeed, a number of studies have reported better voice recognition skills in blind than in sighted adults. The present functional magnetic resonance imaging study investigated changes in the functional organization of neural systems involved in voice identity processing following congenital blindness. A group of congenitally blind individuals and matched sighted control participants were tested in a priming paradigm, in which two voice stimuli (S1, S2) were subsequently presented. The prime (S1) and the target (S2) were either from the same speaker (person‐congruent voices) or from two different speakers (person‐incongruent voices). Participants had to classify the S2 as either a old or a young person. Person‐incongruent voices (S2) compared with person‐congruent voices elicited an increased activation in the right anterior fusiform gyrus in congenitally blind individuals but not in matched sighted control participants. In contrast, only matched sighted controls showed a higher activation in response to person‐incongruent compared with person‐congruent voices (S2) in the right posterior superior temporal sulcus. These results provide evidence for crossmodal plastic changes of the person identification system in the brain after visual deprivation. Hum Brain Mapp 35:4607–4619, 2014. © 2014 Wiley Periodicals, Inc.
Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: Comparison of effects in France and the United States
Authors: Le Berre Anne‐Pascale , Pitel Anne‐Lise , Chanraud Sandra , Beaunieux Hélène , Eustache Francis , Martinot Jean‐Luc , Reynaud Michel , Martelli Catherine , Rohlfing Torsten , Sullivan Edith V. , Pfefferbaum Adolf
Published: March 2014

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1‐weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas‐based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences.Hum Brain Mapp 35:4635–4653, 2014. ©2014 Wiley Periodicals, Inc.
Neonatal atlas construction using sparse representation
Authors: Shi Feng , Wang Li , Wu Guorong , Li Gang , Gilmore John H. , Lin Weili , Shen Dinggang
Published: March 2014

Atlas construction generally includes first an image registration step to normalize all images into a common space and then an atlas building step to fuse the information from all the aligned images. Although numerous atlas construction studies have been performed to improve the accuracy of the image registration step, unweighted or simply weighted average is often used in the atlas building step. In this article, we propose a novel patch‐based sparse representation method for atlas construction after all images have been registered into the common space. By taking advantage of local sparse representation, more anatomical details can be recovered in the built atlas. To make the anatomical structures spatially smooth in the atlas, the anatomical feature constraints on group structure of representations and also the overlapping of neighboring patches are imposed to ensure the anatomical consistency between neighboring patches. The proposed method has been applied to 73 neonatal MR images with poor spatial resolution and low tissue contrast, for constructing a neonatal brain atlas with sharp anatomical details. Experimental results demonstrate that the proposed method can significantly enhance the quality of the constructed atlas by discovering more anatomical details especially in the highly convoluted cortical regions. The resulting atlas demonstrates superior performance of our atlas when applied to spatially normalizing three different neonatal datasets, compared with other start‐of‐the‐art neonatal brain atlases.Hum Brain Mapp 35:4663–4677, 2014. ©2014 Wiley Periodicals, Inc.
Epigenetics in liver disease
Authors: Mann Derek A.
Published: March 2014

Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable. Conclusion: The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade. (Hepatology 2014;60:1418–1425)
Celecoxib: a new augmentation strategy for depressive mood episodes. A systematic review and meta‐analysis of randomized placebo‐controlled trials
Authors: Faridhosseini Farhad , Sadeghi Ramin , Farid Layla , Pourgholami Meysam
Published: March 2014

Objective

The aim of this research was to perform a systematic review to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of add‐on celecoxib for treatment of depressive mood episodes.

Methods

Four electronic databases were systematically searched from their inception to 8 August 2013: PubMed, Cochrane Library (Cochrane Central Register of Controlled Trials), Scopus, and PsychINFO. Pooled difference in means of Hamilton Depression Rating Scale score, pooled odds ratio (OR) of treatment response, and pooled OR of remission were calculated as the main effect size. A random‐effects model was used to pool the data across studies.

Results

Five RCTs (four unipolar depression studies and one bipolar depression study) were included in the systematic review for qualitative data synthesis. Moreover, quantitative results of four RCTs (unipolar depression studies) were meta‐analyzed. The add‐on celecoxib group had a statistically significant decrease in means of the Hamilton Depression Rating Scale score at week 4 (pooled difference in means = 3.3, 95%CI [1.2–5.3],p = 0.002) and week 6 (pooled difference in means = 3.43, 95%CI [1.9–4.9],p < 0.0001). The add‐on celecoxib group also showed higher response (pooledOR = 6.6, 95%CI [2.5–17],p < 0.0001) and remission rates (pooledOR = 6.6, 95%CI [2.7–15.9],p < 0.0001) compared with the placebo group.

Conclusions

Celecoxib can be considered as an effective add‐on treatment for unipolar depressive patients. Making conclusion regarding the efficacy and safety for longer duration warrants further studies with a larger sample size and longer follow‐up duration. Copyright © 2014 John Wiley & Sons, Ltd.
Fast differentiation of SIRS and sepsis from blood plasma of ICU patients using Raman spectroscopy
Authors: Neugebauer Ute , Trenkmann Sabine , Bocklitz Thomas , Schmerler Diana , Kiehntopf Michael , Popp Jürgen
Published: March 2014

Currently, there is no biomarker that can reliable distinguish between infectious and non‐infectious systemic inflammatory response syndrome (SIRS). However, such a biomarker would be of utmost importance for early identification and stratification of patients at risk to initiate timely and appropriate antibiotic treatment.

Within this proof of principle study, the high potential of Raman spectroscopy for the fast differentiation of non‐infectious SIRS and sepsis is demonstrated. Blood plasma collected from 70 patients from the intensive care unit (31 patients with sepsis and 39 patients classified with SIRS without infection) was analyzed by means of Raman spectroscopy. A PCA‐LDA based classification model was trained with Raman spectra from test samples and yielded for sepsis a sensitivity of 1.0 and specificity of 0.82. These results have been confirmed with an independent dataset (prediction accuracy 80%). (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sodium Tungstate: The First Application as Non‐oxidative Catalyst in Organic Synthesis
Authors: Khodabakhshi Saeed , Baghernejad Mojtaba
Published: March 2014

A convenient synthesis of some pyranocoumarins was described via a one‐pot, three‐component reaction of 4‐hydroxyxoumarin, malononitrile and different aromatic aldehydes in the presence of sodium tungstate. This is the first application of sodium tungstate as non‐oxidative catalyst in organic reactions. Simple operation, use of readily available starting materials, good to excellent yields and short reaction times are the advantages of this method for the synthesis of these biologically important products.
Regioselective Synthesis of 1‐Substituted Indazole‐3‐carboxylic Acids
Authors: Veerareddy Arava , Gogireddy Surendrareddy , Dubey P. K.
Published: March 2014

In this article, we study the synthesis of 1‐substituted indazole‐3‐carboxylic acids from 2‐halobenzoic acids.
Aqueous Hydrofluoric Acid Catalyzed Facile Synthesis of 2,3,6‐Substituted Quinoxalines
Authors: Chandra Shekhar A. , Ravi Kumar A. , Sathaiah G. , Raju K. , Srinivas P. V. S. S. , Shanthan Rao P. , Narsaiah B.
Published: March 2014

A versatile synthetic route for the preparation of 2,3,6‐trisubstituted quinoxalines in excellent yield is developed from θ‐diamines and 1,2‐dicarbonyl compounds in which aqueous hydrofluoric acid was employed as the medium and catalyst. Other salient features of this protocol include milder conditions, absence of coupling agents, and easy workup procedures.
Regioselective Synthesis of Polyaza Pyrimidines and Polyaza Pyrazoles under One‐Pot Multicomponent Reaction Conditions
Authors: Singh Okram Mukherjee , Devi Laishram Ronibala , Lim Ki Bum , Lee Sang‐Gyeong
Published: March 2014

Convenient methods of synthesis of novel polyaza pyrimidines and polyaza pyrazoles have been described in this paper. The synthetic method is based on one‐pot, three‐component cyclocondensation of α‐oxoketene dithioacetals, 2,6‐diaminopyridine, and guanidine/hydrazine. Polyaza S,N‐acetals have been generated in situ by treating α‐oxoketene dithioacetals with 2,6‐diaminopyridine in the presence of n‐butyl lithium, which were subsequently treated with guanidine nitrate and hydrazine hydrate to afford polyaza pyrimidines and polyaza pyrazoles, respectively.
An Environmentally Benign Water Promoted Catalyst Free Highly Efficient, One‐pot Synthesis of 2‐Imino‐4‐thiazolidinone
Authors: Kosurkar Umesh B. , Dadmal Tulshiram L. , Kumbhare Ravindra M. , Sridhar Balasubramanian
Published: March 2014

A practical and efficient protocol has been developed for the synthesis of 2‐imino‐4‐thiazolidinone through a unique one pot three‐component reaction of variety of amines, isothiocyanate and ethylbromoacetate in water. The method is free of catalyst and other toxic solvents, has shorter reaction times, high‐yielding, effortlessness in isolation of product, making it more eco‐friendly process, and suitable for large scale operation.
Synthesis and Chemical Reactivity of 4‐Oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde
Authors: Sepay Nayim , Dey Sankar P.
Published: March 2014

4‐Oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde (chromone‐3‐carboxaldehyde or 3‐formylchromone) 1 is an important biologically active compound. It can serve as a precursor in the synthesis of a wide range of heterocyclic systems having chromone moiety, many of which exhibit broad spectrum of biological activities such as anti‐mutagenisity, cytotoxicity, thymidine phosphorylase inhibitor, and anti‐HIV activity. During the last decade, the title compound was studied extensively. The review presents an overall survey of the synthesis, chemical reactivity, and biological activities of 4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes and some of its derivatives.
Distinguishing between renal oncocytoma and chromophobe renal cell carcinoma using Raman molecular imaging
Authors: Stewart Shona , Kirschner Heather , Treado Patrick J. , Priore Ryan , Tretiakova Maria , Cohen Jeffrey K.
Published: March 2014

Raman molecular imaging was evaluated as a tool for differentiating between kidney tumors which are sometimes confused using conventional histopathological methods.

Renal oncocytoma and chromophobe renal cell carcinoma are two kidney tumors which occasionally possess overlapping histological features. There is no reliable alternative method to routine histologic examination for differentiating these neoplasms. However, a conclusive diagnosis is important, as renal oncocytoma is benign and chromophobe renal cell carcinoma has malignant potential, requiring different treatment options.

In an investigation based on 88 patients, a partial least squares discriminant analysis model generated from Raman molecular images distinguished between chromophobe renal cell carcinoma and renal oncocytoma with a performance of 86% sensitivity and 81% specificity.

These initial observations suggest that Raman molecular imaging may be applied not only to the differentiation of these kidney tumors but also to other applications for which conventional histological methods are not sufficient for a conclusive diagnosis. Copyright © 2014 John Wiley & Sons, Ltd.
Traumatic Brain Injury, PTSD, and Current Suicidal Ideation Among Iraq and Afghanistan U.S. Veterans
Authors: Wisco Blair E. , Marx Brian P. , Holowka Darren W. , Vasterling Jennifer J. , Han Sohyun C. , Chen May S. , Gradus Jaimie L. , Nock Matthew K. , Rosen Raymond C. , Keane Terence M.
Published: March 2014

Suicide is a prevalent problem among veterans deployed to Iraq and Afghanistan. Traumatic brain injury (TBI) and psychiatric conditions, such as posttraumatic stress disorder (PTSD), are potentially important risk factors for suicide in this population, but the literature is limited by a dearth of research on female veterans and imprecise assessment of TBI and suicidal behavior. This study examined 824 male and 825 female U.S. veterans who were enrolled in the baseline assessment of the Veterans After‐Discharge Longitudinal Registry (Project VALOR), an observational registry of veterans with and without PTSD who deployed in support of the wars in Iraq and Afghanistan and were enrolled in the Veterans Affairs healthcare system. Results indicated that current depressive symptoms, PTSD, and history of prior TBI were all significantly associated with current suicidal ideation (Cohen's d = 0.91, Cramers’ Vs = .19 and .08, respectively). After adding a number of variables to the model, including psychiatric comorbidity, TBI history was associated with increased risk of current suicidal ideation among male veterans only (RR = 1.55). TBI is an important variable to consider in future research on suicide among veterans of the wars in Iraq and Afghanistan, particularly among male veterans.
Intraoperative hemodialysis during liver transplantation: A decade of experience
Authors: Nadim Mitra K. , Annanthapanyasut Wanwarat , Matsuoka Lea , Appachu Kari , Boyajian Mark , Ji Lingyun , Sedra Ashraf , Genyk Yuri S.
Published: March 2014

Liver transplantation (LT) for patients with renal dysfunction is frequently complicated by major fluid shifts, acidosis, and electrolyte and coagulation abnormalities. Continuous renal replacement therapy (CRRT) has been previously shown to ameliorate these problems. We describe the safety and clinical outcomes of intraoperative hemodialysis (IOHD) during LT for a group of patients with high Model for End-Stage Liver Disease (MELD) scores. We performed a retrospective study at our institution of patients who underwent IOHD from 2002 to 2012. Seven hundred thirty-seven patients underwent transplantation, and 32% received IOHD. The mean calculated MELD score was 37, with 38% having a MELD score ≥ 40. Preoperatively, 61% were in the intensive care unit, 19% were mechanically ventilated, 43% required vasopressor support, and 80% were on some form of renal replacement therapy at the time of transplantation, the majority being on CRRT. Patients on average received 35 U of blood products and 4.8 L of crystalloids without significant changes in hemodynamics or electrolytes. The average urine output was 450 ml, and the average amount of fluid removal with dialysis was 1.8 L. The 90-day patient and dialysis-free survival rates were 90% and 99%, respectively. One-year patient survival rates based on the pretransplant renal replacement status and the MELD status were not statistically different. This is the first large study to demonstrate the safety and feasibility of IOHD in a cohort of critically ill patients with high MELD scores undergoing LT with good patient and renal outcomes. Liver Transpl 20:756-764, 2014. © 2014 AASLD.
Recurrence of primary sclerosing cholangitis in pediatric liver transplant recipients
Authors: Venkat Veena L. , Ranganathan Sarangarajan , Mazariegos George V. , Sun Qing , Sindhi Rakesh
Published: March 2014

There is little detailed clinical information on recurrent primary sclerosing cholangitis (rPSC) after liver transplantation in children. Our purpose was to describe the characteristics of children who had experienced rPSC after liver transplantation so that we could identify potential risk factors for recurrence. Clinical information for pediatric patients undergoing transplantation for primary sclerosing cholangitis (PSC) was retrospectively reviewed, and variables related to the pretransplant diagnosis of PSC and posttransplant variables were abstracted. The studied variables included the following: cytomegalovirus/Epstein-Barr virus status, early/late rejection, induction regimen, immunosuppression in the first year, steroid-resistant rejection, diagnosis of inflammatory bowel disease, and human leukocyte antigen markers commonly associated with PSC. A diagnosis of rPSC was made on the basis of radiographic features, histology, or both. Twelve patients underwent liver transplantation for PSC between 1993 and 2012. Patients received tacrolimus for maintenance immunosuppression after induction with steroids (n = 6) or thymoglobulin (n = 6). Three patients were diagnosed with rPSC 44, 60, and 62 months after transplantation. A fourth patient underwent retransplantation for graft failure with features of both hepatic artery stenosis and rPSC. This patient had distinct histological features of rPSC in the second graft. Three of the 4 patients were 7 years old or younger at the diagnosis of PSC. The patient and graft survival rates were similar for the steroid and thymoglobulin groups. All 4 children with rPSC received steroid-free thymoglobulin induction. In conclusion, our observation of an association between thymoglobulin, and age less than 10 years at the diagnosis of PSC, and rPSC adds to the existing suggestion of a link between the immune environment and the pathogenesis of rPSC. Defining the natural history of rPSC and searching for the etiology and risk factors of rPSC are important for the long-term outcomes of pediatric patients. Liver Transpl 20:679-686, 2014. © 2014 AASLD.
46,XY disorder of sexual development resulting from a novel monoallelic mutation (p.Ser31Phe) in the steroid 5α‐reductase type‐2 (SRD5A2) gene
Authors: Chávez Bertha , Ramos Luis , Gómez Rita , Vilchis Felipe
Published: March 2014

Inactivating mutations of the 5α‐steroid reductase type‐2 (SRD5A2) gene result in a broad spectrum of masculinization defects, ranging from a male phenotype with hypospadias to a female phenotype with Wolffian structures. Molecular studies of the SRD5A2 revealed a new heterozygous gene variant within the coding region that results in phenotypic expression. A c.92C>T transition changing serine to phenylalanine at codon 31 of exon 1 (p.Ser31Phe) was identified in a patient with 46,XY disorder of sexual development who displayed glandular hypospadias with micropenis and bilateral cryptorchidism. The restoration of the p.Ser31Phe mutation by site‐directed mutagenesis and transient expression assays using cultured HEK‐293 cells showed that this novel substitution does not abolish but does deregulate the catalytic efficiency of the enzyme. Thus, the maximum velocity (Vmax) value was higher for the mutant enzyme (22.5 ± 6.9 nmol DHT mg protein−1 h−1) than for the wild‐type enzyme (9.8 ± 2.0 nmol DHT mg protein−1 h−1). Increased in vitro activity of the p.Ser31Phe mutant suggested an activating effect. This case provides evidence that heterozygous missense mutations in SRD5A2 may induce the abnormal development of male external genitalia.
Dynamics of radiation induced γH2AX foci in chromatin subcompartments of mouse pachytene spermatocytes and round spermatids
Authors: Singh Priti , Raman Mercy J.
Published: March 2014

Chromatin compaction is thought to influence the severity of radiation‐induced DNA damage. We assessed how chromatin state affects DNA double‐strand break repair within eu‐/heterochromatin domains in male germ cells by profiling the spatiotemporal dynamics of γ‐radiation‐induced γH2AX foci in confocal images of mouse pachytene spermatocytes and round spermatids (5 min to16 hr post‐irradiation, in vivo). In unirradiated cells, all DNA‐dense heterochromatin domains showed compaction by anti‐H3K9me3‐staining, except for peripheral areas. Following irradiation, this signal was lost within 5 min, but regained later (8–16 hr); these two events coincided with the appearance and loss of γH2AX foci, respectively. While euchromatin showed a large number of bright foci in both cell types, heterochromatin had few foci. In spermatids, a few small, faint foci appeared within chromocenters. Pachytene‐stage, on the other hand, lacked foci within heterochromatin, although a few were closely associated with the heterochromatin periphery. The number of euchromatin foci in spermatids showed a dose‐dependent enhancement following irradiation (0.5–4 Gy), although no significant increase was seen in the quantity of heterochromatin foci. While all foci in pachytene‐stage cells were resolved, spermatids showed large residual foci—especially from heterochromatin foci, which remained faint for up to 4 hr, then increased in size between 8–16 hr, expanding at the chromocenter periphery and eventually protruding into euchromatin at H3K9me3‐signal‐free areas. Thus, this study identified scant foci formation and poor repair within heterochromatin, with distinctly different dynamics in meiotic and post‐meiotic stages of spermatogenesis, and provides direct evidence for heterochromatin decompaction following DNA damage, which facilitates repair/repositioning of foci towards euchromatin domains. It is the first demonstration of spatiotemporal mobilization of double‐strand breaks with respect to chromatin subdomains in male germ cells. Mol. Reprod. Dev. 81: 484–496, 2014. © 2014 Wiley Periodicals, Inc.