bluuebunny/crossref_metadata_2025 huggingface dataset:
FUNDAMENTAL PARTICLE STRUCTURE IN THE COSMOLOGICAL DARK MATTER
Authors: KHLOPOV MAXIM
Published: November 2013

The nonbaryonic dark matter of the universe is assumed to consist of new stable forms of matter. Their stability reflects symmetry of micro-world and mechanisms of its symmetry breaking. Particle candidates for cosmological dark matter are lightest particles that bear new conserved quantum numbers. Dark matter particles may represent ideal gas of noninteracting particles. Self-interacting dark matter weakly or superweakly coupled to ordinary matter is also possible, reflecting nontrivial pattern of particle symmetry in the hidden sector of particle theory. In the early universe the structure of particle symmetry breaking gives rise to cosmological phase transitions, from which macroscopic cosmological defects or primordial nonlinear structures can be originated. Primordial black holes (PBHs) can be not only a candidate for dark matter, but also represent a universal probe for superhigh energy physics in the early universe. Evaporating PBHs turn to be a source of even superweakly interacting particles, while clouds of massive PBHs can serve as nonlinear seeds for galaxy formation. The observed broken symmetry of the three known families may provide a simultaneous solution for the problems of the mass of neutrino and strong CP-violation in the unique framework of models of horizontal unification. Dark matter candidates can also appear in the new families of quarks and leptons and the existence of new stable charged leptons and quarks is possible, hidden in elusive "dark atoms." Such possibility, strongly restricted by the constraints on anomalous isotopes of light elements, is not excluded in scenarios that predict stable double charged particles. The excessive -2 charged particles are bound in these scenarios with primordial helium in O-helium "atoms," maintaining specific nuclear-interacting form of the dark matter, which may provide an interesting solution for the puzzles of the direct dark matter searches. In the context of cosmoparticle physics, studying fundamental relationship of micro- and macro-worlds, the problem of cosmological dark matter implies cross disciplinary theoretical, experimental and observational studies for its solution.
DERIVATION OF GENERALIZED THOMAS–BARGMANN–MICHEL–TELEGDI EQUATION FOR A PARTICLE WITH ELECTRIC DIPOLE MOMENT
Authors: FUKUYAMA TAKESHI , SILENKO ALEXANDER J.
Published: November 2013

General classical equation of spin motion is explicitly derived for a particle with magnetic and electric dipole moments in electromagnetic fields. Equation describing the spin motion relative to the momentum direction in storage rings is also obtained.
WEATHER SHOCKS AND AGRICULTURAL COMMODITY PRICES IN INDIA
Authors: BHANUMURTHY N. R. , DUA PAMI , KUMAWAT LOKENDRA
Published: November 2013

We analyze the impact of weather shocks on price formation in spot and futures market for food in India where until the recent introduction of commodity futures markets in 2005, the transmission of these shocks to short-term (spot) price movements was unclear. Hitherto, the price discovery mechanism was weak and end price was expected to be different (mostly higher unless some product prices were administered) from the market-clearing price. In addition, this weak mechanism was expected to result in higher price volatility. The introduction of a futures market is expected to reduce risk, a major component in agricultural production as well as in price formation. Though the commodity futures market in India is nascent, we model transmission of weather shocks to futures and spot prices using monthly data. Based on cointegration analysis, our results suggest strong long-run co-movement between futures prices and spot prices for commodities traded in futures markets. Changes in rainfall affect both futures and spot prices with different lags. However, rainfall shocks generate larger responses from futures prices than from spot prices. Although there could be other factors that affect futures prices, after controlling for fuel prices, our results clearly show the transmission mechanism of weather shocks from futures to spot prices. We also explore the changes in responsiveness of prices of major agricultural commodities to rainfall with introduction of futures contracts to facilitate the pass-through of various types of shocks to agricultural commodity prices. Using smooth transition regression, we find that the bivariate relationships between rainfall and prices of rice, wheat and pulses show some nonlinearity with the structural change happening after the introduction of futures market. These relations are found to be much stronger in the post-structural change period that broadly coincides with the introduction of futures market.
Protective effects of Notoginsenoside R1 on intestinal ischemia-reperfusion injury in rats
Authors: Li Chong , Li Quan , Liu Yu-Ying , Wang Ming-Xia , Pan Chun-Shui , Yan Li , Chen Yuan-Yuan , Fan Jing-Yu , Han Jing-Yan
Published: November 2013

Intestinal ischemia and reperfusion (I/R) is a clinical problem occurred for diverse causes with high mortality. Prophylaxis and treatment of intestinal I/R remains a challenge for clinicians. The purpose of the present study was to explore the role of Notoginsenoside R1 (R1), a major component form of Panax notoginseng, in management of intestinal I/R injury. Intestinal I/R was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 90 min followed by reperfusion for 60 min or 3 days. R1 (10 mg·kg−1·h−1) was administered either 20 min before ischemia or 20 min after reperfusion. Intestinal microcirculation was evaluated by intravital microscopy over 60 min reperfusion. Sixty minutes or 3 days after reperfusion, rats were killed for histological examination of the jejunum tissue and immunohistochemical localization of myeloperoxidase and CD68. ATP, ADP, and AMP content in jejunum tissue was assessed by ELISA. Activation of nuclear factor-κB (NF-κB) and expression of ATP5D and tight junction proteins were determined by Western blotting. The results demonstrated that R1 is capable of attenuating intestinal I/R-induced microvascular hyperpermeability, inflammatory cytokine production, NF-κB activation, and loss of tight junction proteins, as well as improving energy metabolism during I/R. The results of the present study suggest R1 as an option in protecting against intestinal I/R injury.
XRCC7 rs#7003908 Polymorphism andHelicobacter pyloriInfection-Related Gastric Antrum Adenocarcinoma
Authors: Wang Chao , Huang Xiao-Ying , Yao Jin-Guang , Huang Bing-Chen , Huang Cen-Han , Liao Pinhu , Long Xi-Dai
Published: November 2013

The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated withHelicobacter pylori(H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03–8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89–22.77) for XRCC7-TG and 38.49 (22.82–64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction=1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.
PD-L1 Blockade Attenuated Sepsis-Induced Liver Injury in a Mouse Cecal Ligation and Puncture Model
Authors: Zhu Weimin , Bao Rui , Fan Xiaohua , Tao Tianzhu , Zhu Jiali , Wang Jiafeng , Li Jinbao , Bo Lulong , Deng Xiaoming
Published: November 2013

Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis.
Synthesis, Characterization, and Bioactivity of Schiff Bases and TheirCd2+,Zn2+,Cu2+, andNi2+Complexes Derived from Chloroacetophenone Isomers with S-Benzyldithiocarbazate and the X-Ray Crystal Structure of S-Benzyl-β-N-(4-chlorophenyl)methylenedithiocarbazate
Authors: Break Mohammed Khaled bin , Tahir M. Ibrahim M. , Crouse Karen A. , Khoo Teng-Jin
Published: November 2013

Two bidentate Schiff base ligands having nitrogen sulphur donor sequence were derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 2-chloroacetophenone and 4-chloroacetophenone to give S-benzyl-β-N-(2-chlorophenyl)methylenedithiocarbazate (NS2) and S-benzyl-β-N-(4-chlorophenyl)methylenedithiocarbazate (NS4) isomers. Each of the ligands was then chelated with Cd2+, Zn2+, Cu2+, and Ni2+. The compounds were characterized via IR spectroscopy and melting point while the structure of NS4 was revealed via X-ray crystallography. Finally, the compounds were screened for antimicrobial activity to investigate the effect that is brought by the introduction of the chlorine atom to the benzene ring. X-ray crystallographic analysis showed that the structure of NS4 is planar with a phenyl ring that is nearly perpendicular to the rest of the molecules. The qualitative antimicrobial assay results showed that NS4 and its complexes lacked antifungal activity while Gram-positive bacteria were generally inhibited more strongly than Gram-negative bacteria. Furthermore, NS4 metal complexes were inhibited more strongly than the ligand while the opposite was seen with NS2 ligand and its complexes due to the partial solubility in dimethyl sulfoxide (DMSO). It was concluded that generally NS2 derivatives have higher bioactivity than that of NS4 derivatives and that the Cd complexes of both ligands have pronounced activity specifically onK. rhizophila.
Electrochemiluminescent Detection of Hydrogen Peroxide via Some Luminol Imide Derivatives with Different Substituent Groups
Authors: Jiao Tifeng , Huang Qinqin , Xiao Yong , Shen Xihai , Zhou Jingxin , Gao Faming
Published: November 2013

Some luminol imide derivatives with different substituent groups have been designed and synthesized. Their electrochemiluminescence properties have been measured with a view to developing new biosensors. The ECL response to hydrogen peroxide in the presence of these luminescent derivatives has been investigated taking into account crucial factors such as the applied potential value, injection volume of hydrogen peroxide, and the substituent groups in molecular structures. The experimental data demonstrated that the substituent groups in these imide derivatives can have a profound effect upon the ECL abilities of these studied compounds. The present research work affords new and useful exploration for the design and development of new soft matter for ECL biosensors with luminol functional groups.
Clinical Study on the Prevention of Oxaliplatin-Induced Neurotoxicity with Guilongtongluofang: Results of a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Liu Yunfang , Zhu Guangying , Han Li , Liu Jie , Ma Ting , Yu Huiming
Published: November 2013

Objective. Oxaliplatin-induced peripheral neurotoxicity continues to be a kind of frequent dose-limiting toxicity for many cancer patients. This study evaluated the preventive effects of Guilongtongluofang on peripheral neurotoxicity induced by oxaliplatin in patients with colorectal tumor.Patients and Methods. From May 2007 to May 2011, we conducted a randomized, double-blind, placebo-controlled trial. 120 patients of colorectal cancer treated with adjuvant oxaliplatin-based chemotherapy were randomly enrolled into the trial group and the control group. The trial group received Guilongtongluofang (at a dose of 200 mL once a day) from 3 days prior to chemotherapy. The control group received a placebo from 3 days prior to chemotherapy. Every 2-week cycle, neurotoxicity was evaluated using numeric rating scale for pain intensity and experienced relief. The primary endpoint was efficacy measurement which included oxaliplatin-induced neurotoxicity and tumor response. The differences of side effects between the two groups were also analyzed.Results. The percentage of grades 1-2 neurotoxicity was significantly lower in the trial group than that in the control group (13.3% versus 20.0%;P<0.05) after two cycles of treatment. The difference of the percentage of neurotoxicity between the two groups was significant after six cycles (51.7% versus 70.0%;P<0.05). Significant difference for the mean time to the development of grade 1+ neurotoxicity was found between the two groups (9.4 w in the trial group versus 6.5 w in the control group,P<0.05). The cumulative incidence of grade 1 or more sensory neurotoxicity was significantly lower in the trial group than that in the control group (P<0.05). No significant differences of tumor response rate were found between the two groups the trial group and the control group. No significant difference was found between the trial group and the control group (allP>0.05).Conclusion. This study provides evidence that Guilongtongluofang is a promising drug for the prevention of oxaliplatin-induced neurotoxicity in patients with colorectal cancer, and it does not reduce the efficacy of oxaliplatin.
Nonlinear Dynamics and Chaos in Fractional-Order Hopfield Neural Networks with Delay
Authors: Huang Xia , Wang Zhen , Li Yuxia
Published: November 2013

A fractional-order two-neuron Hopfield neural network with delay is proposed based on the classic well-known Hopfield neural networks, and further, the complex dynamical behaviors of such a network are investigated. A great variety of interesting dynamical phenomena, including single-periodic, multiple-periodic, and chaotic motions, are found to exist. The existence of chaotic attractors is verified by the bifurcation diagram and phase portraits as well.
A Region Growing Vessel Segmentation Algorithm Based on Spectrum Information
Authors: Jiang Huiyan , He Baochun , Fang Di , Ma Zhiyuan , Yang Benqiang , Zhang Libo
Published: November 2013

We propose a region growing vessel segmentation algorithm based on spectrum information. First, the algorithm does Fourier transform on the region of interest containing vascular structures to obtain its spectrum information, according to which its primary feature direction will be extracted. Then combined edge information with primary feature direction computes the vascular structure’s center points as the seed points of region growing segmentation. At last, the improved region growing method with branch-based growth strategy is used to segment the vessels. To prove the effectiveness of our algorithm, we use the retinal and abdomen liver vascular CT images to do experiments. The results show that the proposed vessel segmentation algorithm can not only extract the high quality target vessel region, but also can effectively reduce the manual intervention.
Vertical Spindle Grinding of Si and Granite with a New Abrasive Disk
Authors: Yu Yiqing , Liu Juan , Kuang Bin , Shen Jianyun , Xu Xipeng
Published: November 2013

An investigation was reported of a new attempt in the fabrication of an ultrafine abrasive tool for vertical spindle grinding. The principle of sol-gel was applied to granulate ultra-fine abrasives in order to reduce their aggregation. The granulated abrasives were then added to resin bonds, thereby forming ultra-fine abrasive grinding disks. Before grinding, the disks were dressed to expected flatness using a brazed diamond pad. The dressed grinding disks were then used to grind silicon wafers and natural granite. Both dressing and grinding were conducted on a high precision vertical spindle grinding machine. After grinding, the morphologies of the workpiece materials were examined. With regard to the different concerns for silicon wafers and granite, surface roughness was measured for the silicon wafers and gloss readings were measured for the granite surfaces. It was found that the brazed diamond abrasives could dress the grinding disks with high efficiency and satisfactory flatness. The new ultra-fine abrasive disks were found to be able to process silicon wafers and granite slabs to acceptable results.
Mechanism Simulation and Optimal Design of Five-Link Bionic Joint Driven by Two Antagonistic Pneumatic Muscles
Authors: Wang Binrui , Jin Yinglian , Yan Tianhong , Cheng Miao
Published: November 2013

The five-link parallel mechanism is proposed to improve joint bionic performance, and the kinematics is established for the closed chain joint actuated by two antagonistic artificial pneumatic muscles (PMs). Interference and singularity constraints are analyzed, and the joint torque model is given based on the spring-damp dynamics. Through extracting the spring force term from torque equations, the compliance of bionic joint is derived and expressed as the ratio of angle to spring torque. Energy consumption is analyzed using the PM length varying. Based on MATLAB/SimMechanics, the relationships between the axil installation parameters and swing performances are illustrated through the simulations, including the effect of the installation height and width varying on the angle scope, swing response, compliance, and energy consumption. The bionic shoulder and elbow joints are optimally designed. Compared to the conventional joints, the swing angular range of the proposed joints is enhanced, and the contraction amount of PMs is reduced. The optimal mechanism is more humanoid.
Nonrigid Registration of Lung CT Images Based on Tissue Features
Authors: Zhang Rui , Zhou Wu , Li Yanjie , Yu Shaode , Xie Yaoqin
Published: November 2013

Nonrigid image registration is a prerequisite for various medical image process and analysis applications. Much effort has been devoted to thoracic image registration due to breathing motion. Recently, scale-invariant feature transform (SIFT) has been used in medical image registration and obtained promising results. However, SIFT is apt to detect blob features. Blobs key points are generally detected in smooth areas which may contain few diagnostic points. In general, diagnostic points used in medical image are often vessel crossing points, vascular endpoints, and tissue boundary points, which provide abundant information about vessels and can reflect the motion of lungs accurately. These points generally have high gradients as opposed to blob key points and can be detected by Harris. In this work, we proposed a hybrid feature detection method which can detect tissue features of lungs effectively based on Harris and SIFT. In addition, a novel method which can remove mismatched landmarks is also proposed. A series of thoracic CT images are tested by using the proposed algorithm, and the quantitative and qualitative evaluations show that our method is statistically significantly better than conventional SIFT method especially in the case of large deformation of lungs during respiration.
Experimental Study of the Performance of Air Source Heat Pump Systems Assisted by Low-Temperature Solar-Heated Water
Authors: Wu Jinshun , Chen Chao , Pan Song , Wei Jun , Pan Tianquan , Wei Yixuan , Wang Yunmo , Wang Xinru , Su Jiale
Published: November 2013

Due to the low temperatures, the heating efficiency of air source heat pump systems during the winter is very low. To address this problem, a low-temperature solar hot water system was added to a basic air source heat pump system. Several parameters were tested and analyzed. The heat collection efficiency of the solar collector was analyzed under low-temperature conditions. The factors that affect the performance of the heat pumps, such as the fluid temperature, pressure, and energy savings, were analyzed for cases where the solar energy auxiliary heat pump and the air source heat pump are used independently. The optimal heating temperature and the changes in the fluid temperature were determined. The influence of the compression ratio and the coefficient of performance (COP) were investigated theoretically. The results revealed the parameters that are important to the performance of the system. Several measures for improving the COP of the heat pump units are provided for other applications and future research.
Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection
Authors: Pan Ning , Qiu Jie , Sun Hang , Miao Fengqin , Shi Qian , Xu Jinhuan , Jiang Wei , Jin Hui , Xie Wei , He Youji , Zhang Jianqiong
Published: November 2013

To investigate whether killer cell immunoglobulin-like receptor(KIR)and human leukocyte antigen(HLA)genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci ofKIRwas detected individually.HLA-A, -B, and -Cloci were genotyped with high resolution by a routine sequence-based typing method. The effect of eachKIRlocus,HLAligand, andHLA-KIRcombination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identifiedC1C1-KIR2DS2/2DL2as an independent risk factor for earlier onset age of HCC (median onset age was 44 forC1C1-KIR2DS2/2DL2positive patients compared to 50 for negative patients,P=0.04for KM analysis; HR = 1.70,P=0.004for multivariate Cox model). We conclude thatKIRandHLAgenetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or otherKIR-expressing cells) in the progress of HBV-related HCC development.
Surface State Capture Cross-Section at the Interface between Silicon and Hafnium Oxide
Authors: Chiu Fu-Chien
Published: November 2013

The interfacial properties between silicon and hafnium oxide (HfO2) are explored by the gated-diode method and the subthreshold measurement. The density of interface-trapped charges, the current induced by surface defect centers, the surface recombination velocity, and the surface state capture cross-section are obtained in this work. Among the interfacial properties, the surface state capture cross-section is approximately constant even if the postdeposition annealing condition is changed. This effective capture cross-section of surface states is about 2.4 × 10−15 cm2, which may be an inherent nature in the HfO2/Si interface.
Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer
Authors: Jansen Maurice P.H.M. , Knijnenburg Theo , Reijm Esther A. , Simon Iris , Kerkhoven Ron , Droog Marjolein , Velds Arno , van Laere Steven , Dirix Luc , Alexi Xanthippi , Foekens John A. , Wessels Lodewyk , Linn Sabine C. , Berns Els M.J.J. , Zwart Wilbert
Published: November 2013

Aromatase inhibitors are the major first-line treatment of estrogen receptor–positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor α (ERα), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ERα, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ERα and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor–treated patients. Through this approach, we determined that the ERα and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. Cancer Res; 73(22); 6632–41. ©2013 AACR.
The Human Gut Microbiome and Its Dysfunctions
Authors: Mondot Stanislas , de Wouters Tomas , Doré Joël , Lepage Patricia
Published: November 2013

The human gastrointestinal tract hosts more than 100 trillion bacteria and archaea, which together make up the gut microbiota. The amount of bacteria in the human gut outnumbers human cells by a factor of 10, but some finely tuned mechanisms allow these microorganisms to colonize and survive within the host in a mutual relationship. The human gut microbiota co-evolved with humans to achieve a symbiotic relationship leading to physiological homeostasis. The microbiota provides crucial functions that human cannot exert themselves while the human host provides a nutrient-rich environment. Chaotic in the early stages of life, the assembly of the human gut microbiota remains globally stable over time in healthy conditions and absence of perturbation. Following perturbation, such as antibiotic treatment, bacteria will recolonize the niches with a composition and diversity similar to the basal level since the ecosystem is highly resilient. Yet, recurrent perturbations lead to a decrease in resilience capacity of the gut microbiome. Shifts in the bacterial composition and diversity of the human gut microbiota have been associated with intestinal dysfunctions such as inflammatory bowel disease and obesity. More than specific bacteria, a general destructuration of the ecosystem seems to be involved in these pathologies. Application of metagenomics to this environment may help in deciphering key functions and correlation networks specifically involved in health maintenance. In term, fecal transplant and synthetic microbiome transplant might be promising therapies for dysbiosis-associated diseases.
Targeting T and B Lymphocytes in Inflammatory Bowel Diseases: Lessons from Clinical Trials
Authors: Gerner R.R. , Moschen A.R. , Tilg H.
Published: November 2013

Both innate and adaptive immunity play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). There is strong evidence that especially activated T cells initiate and perpetuate inflammation and tissue destruction. The increased numbers of CD4+ T cells in the intestinal wall of IBD patients may be explained by enhanced influx/activation and decreased apoptosis of these cells. Several studies have demonstrated that the gut-homing receptors CCR9 and α4β7 are selectively induced on T cells during their priming in intestinal inflamed sites. Whereas targeting of activated CD4+ T cells by specific antibody strategies or neutralization of key T-cell cytokines such as IL-2 or IFN-γ has not been effective in human IBD, blocking migration of activated leukocytes, e.g. T cells into the inflamed tissue by specific antibodies such as vedolizumab, seems highly effective. Recently it could also been demonstrated that administration of antigen-specific regulatory T cells to patients with refractory Crohn's disease was not only well tolerated but showed promising results. The role of B cells in human IBD is less clear. B-cell depletion has so far only been studied in ulcerative colitis where rituximab (anti-CD20) therapy failed. Therefore, although the therapeutic targeting of ‘inflammatory' T and B cells was not successful in IBD, especially T cells remain key players in IBD. Targeting either T-cell migration or the use of regulatory T cells appears as the most promising ‘T-cell-directed' therapies in the future.
Update Imaging in Inflammatory Bowel Diseases
Authors: Herfarth Hans
Published: November 2013

Imaging is a central component of the diagnostic process in inflammatory bowel diseases. This review summarizes the recent progress of various most commonly used imaging modalities including computed tomography enterography, magnetic resonance enterography and capsule endoscopy. Advantages and disadvantages of each imaging protocol in suspected and established inflammatory bowel diseases are reviewed and brought into context in proposed diagnostic algorithms.
Endoscopy as a Prognostic Marker in Inflammatory Bowel Disease
Authors: Camus Marine , Pariente Benjamin , Dray Xavier , Allez Matthieu , Marteau Philippe
Published: November 2013

In patients suffering from reflux esophagitis, the severity of the lesions helps to predict the prognosis and adapt treatment. We herein review the data which suggest that endoscopy also has a prognostic value in inflammatory bowel disease. In the 1990s, the general opinion, based on a few studies, was that assessing endoscopic lesions was not critical for the management of inflammatory bowel disease. The more recent therapeutic strategies using less steroids but purine analogs and anti-TNF antibodies have led to a higher chance of mucosal healing (MH), and there is growing evidence that reaching healing of lesions is of good prognostic value both in ulcerative colitis and Crohn's disease. There is a lower risk of hospitalization and of surgery in patients with MH than in those without healing. There is also a (moderately) lower risk of relapse after stopping treatments in patients with MH than in those with persistent lesions. The risk of cancer (on a long-term basis) also seems be lower in patients with controlled inflammatory lesions than in subjects with persistent inflammation. There are still many unanswered questions, the major one being what is the best treatment choice when MH is not reached?
Treatment Guidelines in Inflammatory Bowel Disease: The Japanese Perspectives
Authors: Matsuoka Katsuyoshi , Hibi Toshifumi
Published: November 2013

The number of inflammatory bowel disease patients has been increasing in Japan and the demand for clinical practical guidelines emerged. A set of clinical practice guidelines for ulcerative colitis and Crohn's disease were thus published in 2006 and 2011, respectively. Their English versions were then published in 2000 and 2012, respectively. These guidelines aim to provide appropriate clinical indicators to Japanese practitioners to improve the outcomes of inflammatory bowel disease patients. The guidelines are based on global literature-based evidence as well as evidence from Japan. The Japanese guidelines were developed based on the existing evidence with integration of the experts' consensus. The criteria for recommendation grade were also determined by the level of evidence as well as by the experts' consensus. It is a distinct feature of the Japanese guidelines to disclose this process explicitly. This recommendation rating is thus useful to fill the gap between evidence and daily clinical practice. Since the Japanese guidelines are primarily based on global literature-based evidence, most of the clinical indicators in them are consistent with those in other guidelines from the Western world. Meanwhile, there are some distinctly different statements in the Japanese guidelines reflecting Japanese standard clinical practice, evidence, and the opinions of Japanese experts.
Trichuris suis Ova in Inflammatory Bowel Disease
Authors: Schölmerich Jürgen
Published: November 2013

Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.
Intestinal Stem Cells
Authors: Stange Daniel E.
Published: November 2013

The intestine has become a prime model system to study stem cell biology. Intestinal stem cells can be identified based on the expression of a unique marker gene, namely Lgr5. A transgenic mouse model expressing green fluorescent protein in intestinal stem cells has allowed their visualization, isolation, molecular characterization and use in generating organoids: small mini-guts that contain all cell types of the intestine. Detailing the behavior of intestinal stem cells has also led to new insights concerning the mechanism of self-renewal versus differentiation. Genes and pathways directing daughter cells of stem cells towards the differentiated lineages of the intestine are getting better defined. Of all differentiated cells, Paneth cells play a distinguished role: they emerged from pure bystanders to the guardians of the stem cell. Taken together, a detailed molecular picture emerges that describes the mechanisms of intestinal homeostatic self-renewal and outlines new therapeutic avenues.
High Rate of Symptomatic Cytomegalovirus Infection in Extremely Low Gestational Age Preterm Infants of 22-24 Weeks' Gestation after Transmission via Breast Milk
Authors: Mehler Katrin , Oberthuer André , Lang-Roth Ruth , Kribs Angela
Published: November 2013

Background: Very immature preterm infants are at risk of developing symptomatic or severe infection if cytomegalovirus is transmitted via breast milk. It is still a matter of debate whether human cytomegalovirus (HCMV) infection may lead to long-term sequelae. Objectives: We hypothesized that symptomatic and severe HCMV infection transmitted via breast milk affects extremely immature infants at a very high rate. Methods: In 2012, untreated breast milk was fed to extremely low birth weight infants after parental informed consent was obtained. We retrospectively analyzed data on HCMV infection of infants born in 2012 between 22 and 24 weeks of gestation. Results: 17 infants were born to HCMV IgG-seropositive mothers. 11 (65%) of these were diagnosed with symptomatic infection. In all cases, thrombocytopenia was the reason to analyze the infant's urine. HCMV infection was diagnosed at a median time of 12 weeks after birth. In 5 (45%) infants, thrombocytopenia was the only symptom and resolved without antiviral therapy or platelet transfusion. 6 (55%) infants developed sepsis-like disease with mildly elevated CRP values and showed signs of respiratory failure. 3 (27%) were able to be stabilized on CPAP, 3 (27%) had to be intubated and mechanically ventilated. 4 children were treated with ganciclovir and/or valganciclovir. 55% failed otoacoustic emissions and/or automated auditory brainstem response testing at discharge. Conclusions: In very immature infants born at the border of viability and suffering from multiple preexisting problems, HCMV infection may trigger a severe deterioration of the clinical course.
Stroke Prenotification Is Associated with Shorter Treatment Times for Warfarin-Associated Intracerebral Hemorrhage
Authors: Dowlatshahi Dar , Wasserman Jason K. , Butcher Ken S. , Bernbaum Manya L. , Cwinn A. Adam , Giulivi Antonio , Lang Eddy , Poon Man-Chiu , Tomchishen-Pope Jessica , Sharma Mukul , Coutts Shelagh B.
Published: November 2013

Background: Warfarin-associated intracerebral hemorrhage (WAICH) is a devastating disease with increasing incidence. In this setting, treatment with prothrombin complex concentrates (PCC) is essential to correct coagulopathy. Yet despite the availability of coagulopathy correction strategies, significant treatment delays can occur in emergency departments (EDs), which may be overcome using stroke prenotification strategies. To explore this, we compared arrival-to-treatment times with PCC for WAICH between two different stroke response systems that used the same international normalized ratio (INR) correction protocol. Methods: We established a registry of consecutive patients presenting with WAICH and treated with PCC presenting to two Canadian tertiary-care academic stroke centers: one with a stroke prenotification system, and one with a traditional ED assessment, treatment and referral system. In this comparative cohort design, we defined the WAICH diagnosis time as the earliest time point where both INR and CT were available. We compared median times from arrival to treatment, as well as arrival to diagnosis, and diagnosis to treatment. Results: Between 2008 and 2010, we collected data from 123 consecutive patients with intracranial hemorrhage who received PCC for INR correction (79 from ED referral, and 44 prenotification). Onset-to-arrival times, demographics, Glasgow Coma Scale scores, and baseline INR were similar between the two systems. Arrival-to-treatment times were significantly shorter in the prenotification system as compared to the traditional ED referral system (135 vs. 267 min; p = 0.001), which was driven by both decreased arrival-to-diagnosis time (49 vs. 117 min; p = 0.006), as well as decreased diagnosis-to-treatment time (56 vs. 112 min; p < 0.001). Arrival-to-scan times and arrival-to-INR times were similarly shorter in the prenotification system (68 vs. 118 min and 20.5 vs. 47 min, respectively). Conclusion: Stroke prenotification was associated with shorter arrival-to-treatment times for emergent INR correction in patients with WAICH, which was driven by both faster diagnosis and treatment. Our results are consistent with those seen in ischemic stroke, suggesting that prenotification systems present an opportunity to optimize acute intracerebral hemorrhage therapy.
Effects of Airborne Birch Pollen Levels on Clinical Symptoms of Seasonal Allergic Rhinoconjunctivitis
Authors: Caillaud Denis , Martin Sylvie , Segala Claire , Besancenot Jean-Pierre , Clot Bernard , Thibaudon Michel ,   on behalf of the French Aerobiology Network
Published: November 2013

Background: Most panel studies focusing on rhinitis and conjunctivitis symptoms and birch pollen have been performed on a linear basis and have not included air pollution and meteorological variables as potential confounders. The objective of this panel study was to assess the relationship between symptoms of seasonal allergic rhinoconjunctivitis and daily airborne birch pollen concentrations, checking with adequate statistical tools the shapes of concentration-response curves and controlling for confounders. Methods: The severity of rhinitis, conjunctivitis, and bronchial symptoms was recorded daily in March and April 2010 (3,311 person-days) in 61 seasonal allergic rhinoconjunctivitis patients sensitized to birch. Data were analyzed with generalized additive and generalized estimating equation models to quantify the effects of birch pollens. Results: The relationship between birch pollen and the percentage of patients with nasal, ocular and bronchial symptoms was linear until birch daily average concentrations of, respectively, 110, 70, and 70 grains/m3; it reached a plateau thereafter. For an increase of 10 grains/m3, the OR (95% CI) for nasal, ocular, and bronchial symptoms were, respectively, 1.07 (1.03-1.12), 1.17 (1.08-1.27), and 1.12 (1.03-1.21). At the beginning of the season, no nasal or ocular symptoms were observed below a threshold of 30 grains/m3. Conclusions: Adequate modeling regression shows that the clinical response to natural exposure to birch pollen in sensitized patients varies during Betula pollen season, with a threshold at the beginning of the season, while over the whole season the relationship is linear for nasal, ocular, and bronchial symptoms up to a saturation point, followed by a plateau.
Neuroretinitis with Branch Retinal Artery Occlusion in a 15-Year-Old Female
Authors: Ahmadi Sina , Azizi Behrooz , Tsang Adrian C. , Coupland Stuart , Gottlieb Chloe , Zackon David
Published: November 2013

We report a case of Bartonella henselae neuroretinitis with significant disc and peripapillary edema, branch retinal artery occlusion without macula involvement and well preserved central vision. A 15-year-old female presented with loss of vision over 4 weeks in the left eye. She had a history of cat exposure, but a cat scratch, insect bite or conjunctivitis was not reported. An inferotemporal arcuate scotoma developed during the acute phase and persisted over the course of the follow-up.
Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation
Authors: Münzer Patrick , Borst Oliver , Walker Britta , Schmid Evi , Feijge Marion A. H. , Cosemans Judith M. E. M. , Chatterjee Madhumita , Schmidt Eva-Maria , Schmidt Sebastian , Towhid Syeda T. , Leibrock Christina , Elvers Margitta , Schaller Martin , Seizer Peter , Ferlinz Klaus , May Andreas E. , Gulbins Erich , Heemskerk Johan W. M. , Gawaz Meinrad , Lang Florian
Published: November 2013

Objective—

Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation.

Approach and Results—

Collagen-related peptide–induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (
Smpd1
−/−
) when compared with platelets from wild-type mice (
Smpd1

+/+

). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in
Smpd1
−/−
platelets than in
Smpd1

+/+

platelets. In contrast, platelet integrin α
IIb
β
3
activation and aggregation, as well as activation-dependent Ca
2+
flux, were not significantly different between
Smpd1
−/−
and
Smpd1

+/+

platelets. In vitro thrombus formation at shear rates of 1700 s
−1
and in vivo thrombus formation after FeCl
3
injury were significantly blunted in
Smpd1
−/−
mice while bleeding time was unaffected. Asm-deficient platelets showed significantly reduced activation-dependent ceramide formation, whereas exogenous ceramide rescued diminished platelet secretion and thrombus formation caused by Asm deficiency. Treatment of
Smpd1

+/+

platelets with bacterial sphingomyelinase (0.01 U/mL) increased, whereas treatment with functional acid sphingomyelinase-inhibitors, amitriptyline or fluoxetine (5 μmol/L), blunted activation-dependent platelet degranulation, phosphatidylserine exposure, and thrombus formation. Impaired degranulation and thrombus formation of
Smpd1
−/−
platelets were again overcome by exogenous bacterial sphingomyelinase.

Conclusions—

Acid sphingomyelinase is a completely novel element in the regulation of platelet plasma membrane properties, secretion, and thrombus formation.
Impact of Nonischemic Scar Features on Local Ventricular Electrograms and Scar-Related Ventricular Tachycardia Circuits in Patients With Nonischemic Cardiomyopathy
Authors: Sasaki Takeshi , Miller Christopher F. , Hansford Rozann , Zipunnikov Vadim , Zviman Menekhem M. , Marine Joseph E. , Spragg David , Cheng Alan , Tandri Harikrishna , Sinha Sunil , Kolandaivelu Aravindan , Zimmerman Stefan L. , Bluemke David A. , Tomaselli Gordon F. , Berger Ronald D. , Halperin Henry R. , Calkins Hugh , Nazarian Saman
Published: November 2013

Background—

The association of local electrogram features with scar morphology and distribution in nonischemic cardiomyopathy has not been investigated. We aimed to quantify the association of scar on late gadolinium-enhanced cardiac magnetic resonance with local electrograms and ventricular tachycardia circuit sites in patients with nonischemic cardiomyopathy.

Methods and Results—

Fifteen patients with nonischemic cardiomyopathy underwent late gadolinium-enhanced cardiac magnetic resonance before ventricular tachycardia ablation. The transmural extent and intramural types (endocardial, midwall, epicardial, patchy, transmural) of scar were measured in late gadolinium-enhanced cardiac magnetic resonance short-axis planes. Electroanatomic map points were registered to late gadolinium-enhanced cardiac magnetic resonance images. Myocardial wall thickness, scar transmurality, and intramural scar types were independently associated with electrogram amplitude, duration, and deflections in linear mixed-effects multivariable models, clustered by patient. Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (
P
<0.0001 by ANOVA) and in regions with patchy scar (versus endocardial, midwall, epicardial scar;
P
<0.05 by ANOVA). Most ventricular tachycardia circuit sites were located in scar with >25% scar transmurality.

Conclusions—

Electrogram features are associated with scar morphology and distribution in patients with nonischemic cardiomyopathy. Previous knowledge of electrogram image associations may optimize procedural strategies including the decision to obtain epicardial access.
Spatial Profiles of Electrical Mismatch Determine Vulnerability to Conduction Failure Across a Host–Donor Cell Interface
Authors: Kirkton Robert D. , Badie Nima , Bursac Nenad
Published: November 2013

Background—

Electrophysiological mismatch between host cardiomyocytes and donor cells can directly affect the electrical safety of cardiac cell therapies; however, the ability to study host–donor interactions at the microscopic scale in situ is severely limited. We systematically explored how action potential (AP) differences between cardiomyocytes and other excitable cells modulate vulnerability to conduction failure in vitro.

Methods and Results—

AP propagation was optically mapped at 75 μm resolution in micropatterned strands (n=152) in which host neonatal rat ventricular myocytes (AP duration=153.2±2.3 ms, conduction velocity=22.3±0.3 cm/s) seamlessly interfaced with genetically engineered excitable donor cells expressing inward rectifier potassium (Kir2.1) and cardiac sodium (Na
v
1.5) channels with either weak (conduction velocity=3.1±0.1 cm/s) or strong (conduction velocity=22.1±0.4 cm/s) electrical coupling. Selective prolongation of engineered donor cell AP duration (31.9–139.1 ms) by low-dose BaCl
2
generated a wide range of host–donor repolarization time (RT) profiles with maximum gradients (∇RT
max
) of 5.5 to 257 ms/mm. During programmed stimulation of donor cells, the vulnerable time window for conduction block across the host–donor interface most strongly correlated with ∇RT
max
. Compared with well-coupled donor cells, the interface composed of poorly coupled cells significantly shortened the RT profile width by 19.7% and increased ∇RT
max
and vulnerable time window by 22.2% and 19%, respectively. Flattening the RT profile by perfusion of 50 μmol/L BaCl
2
eliminated coupling-induced differences in vulnerability to block.

Conclusions—

Our results quantify how the degree of electrical mismatch across a cardiomyocyte–donor cell interface affects vulnerability to conduction block, with important implications for the design of safe cardiac cell and gene therapies.