bluuebunny/crossref_metadata_2025 huggingface dataset:
A Derived Network-Based Interferon-Related Signature of Human Macrophages Responding toMycobacterium tuberculosis
Authors: Wu Kang , Fang Hai , Lyu Liang-Dong , Lowrie Douglas B. , Wong Ka-Wing , Fan Xiao-Yong
Published: August 2014

Network analysis of transcriptional signature typically relies on direct interaction between two highly expressed genes. However, this approach misses indirect and biological relevant interactions through a third factor (hub). Here we determine whether a hub-based network analysis can select an improved signature subset that correlates with a biological change in a stronger manner than the original signature. We have previously reported an interferon-related transcriptional signature (THP1r2Mtb-induced) fromMycobacterium tuberculosis(M. tb)-infected THP-1 human macrophage. We selected hub-connected THP1r2Mtb-induced genes into the refined network signature TMtb-iNet and grouped the excluded genes into the excluded signature TMtb-iEx. TMtb-iNet retained the enrichment of binding sites of interferon-related transcription factors and contained relatively more interferon-related interacting genes when compared to THP1r2Mtb-induced signature. TMtb-iNet correlated as strongly as THP1r2Mtb-induced signature on a public transcriptional dataset of patients with pulmonary tuberculosis (PTB). TMtb-iNet correlated more strongly in CD4+and CD8+T cells from PTB patients than THP1r2Mtb-induced signature and TMtb-iEx. When TMtb-iNet was applied to data during clinical therapy of tuberculosis, it resulted in the most pronounced response and the weakest correlation. Correlation on dataset from patients with AIDS or malaria was stronger for TMtb-iNet, indicating an involvement of TMtb-iNet in these chronic human infections. Collectively, the significance of this work is twofold: (1) we disseminate a hub-based approach in generating a biologically meaningful and clinically useful signature; (2) using this approach we introduce a new network-based signature and demonstrate its promising applications in understanding host responses to infections.
Stochastic Dominance under the Nonlinear Expected Utilities
Authors: Xiao Xinling
Published: August 2014

In 1947, von Neumann and Morgenstern introduced the well‐known expected utility and the related axiomatic system (see von Neumann and Morgenstern (1953)). It is widely used in economics, for example, financial economics. But the well‐known Allais paradox (see Allais (1979)) shows that the linear expected utility has some limitations sometimes. Because of this, Peng proposed a concept of nonlinear expected utility (see Peng (2005)). In this paper we propose a concept of stochastic dominance under the nonlinear expected utilities. We give sufficient conditions on which a random choice X stochastically dominates a random choice Y under the nonlinear expected utilities. We also provide sufficient conditions on which a random choice X strictly stochastically dominates a random choice Y under the sublinear expected utilities.
An Intrinsic Characterization of Bonnet Surfaces Based on a Closed Differential Ideal
Authors: Bracken Paul
Published: August 2014

The structure equations for a two-dimensional manifold are introduced and two results based on the Codazzi equations pertinent to the study of isometric surfaces are obtained from them. Important theorems pertaining to isometric surfaces are stated and a theorem due to Bonnet is obtained. A transformation for the connection forms is developed. It is proved that the angle of deformation must be harmonic, and that the differentials of many of the important variables generate a closed differential ideal. This implies that a coordinate system exists in which many of the variables satisfy particular ordinary differential equations, and these results can be used to characterize Bonnet surfaces.
A Review on the Relationship between SGLT2 Inhibitors and Cancer
Authors: Lin Hao-Wen , Tseng Chin-Hsiao
Published: August 2014

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.
Nutritional Recovery Promotes Hypothalamic Inflammation in Rats during Adulthood
Authors: Silva Hellen Barbosa Farias , de Almeida Ana Paula Carli , Cardoso Katarine Barbosa , Ignacio-Souza Letícia Martins , Reis Silvia Regina de Lima , Reis Marise Auxiliadora de Barros , Latorraca Márcia Queiroz , Milanski Marciane , Arantes Vanessa Cristina
Published: August 2014

We evaluated whether protein restriction in fetal life alters food intake and glucose homeostasis in adulthood by interfering with insulin signal transduction through proinflammatory mechanisms in the hypothalamus and peripheral tissues. Rats were divided into the following: a control group (C); a recovered group (R); and a low protein (LP) group. Relative food intake was greater and serum leptin was diminished in LP and R compared to C rats. Proinflammatory genes and POMC mRNA were upregulated in the hypothalamus of R group. Hypothalamic NPY mRNA expression was greater but AKT phosphorylation was diminished in the LP than in the C rats. In muscle, AKT phosphorylation was higher in restricted than in control animals. The HOMA-IR was decreased in R and C compared to the LP group. In contrast, theKittin R was similar to that in C and both were lower than LP rats. Thus, nutritional recovery did not alter glucose homeostasis but produced middle hyperphagia, possibly due to increased anorexigenic neuropeptide expression that counteracted the hypothalamic inflammatory process. In long term protein deprived rats, hyperphagia most likely resulted from increased orexigenic neuropeptide expression, and glucose homeostasis was maintained, at least in part, at the expense of increased muscle insulin sensitivity.
Aging and Others’ Pain Processing: Implications for Hospitalization
Authors: Di Domenico Alberto , Fairfield Beth , Mammarella Nicola
Published: August 2014

Objectives. While self-pain perception has been widely investigated in aging, the perception as well as memory of pain in others has received little attention.Methods. The study was designed as a cross-sectional behavioral study in which a group of 41 younger and a group of 41 older adults evaluated a series of valenced and pain-related pictures and were later required to recall them.Results. We found that older adults judge the stimuli as being less intense compared to their younger counterparts. However, older adults remembered a larger number of pictures with individuals expressing pain compared to pictures with individuals who have neutral or positive facial expressions.Conclusions. Older adults may underestimate emotional intensity in others, but they seem to remember painful information in others as well as younger adults. These data are discussed in terms of theories of pain perception and implications for hospitalization.
Comparing Evolutionary Strategies on a Biobjective Cultural Algorithm
Authors: Lagos Carolina , Crawford Broderick , Cabrera Enrique , Soto Ricardo , Rubio José-Miguel , Paredes Fernando
Published: August 2014

Evolutionary algorithms have been widely used to solve large and complex optimisation problems. Cultural algorithms (CAs) are evolutionary algorithms that have been used to solve both single and, to a less extent, multiobjective optimisation problems. In order to solve these optimisation problems, CAs make use of different strategies such as normative knowledge, historical knowledge, circumstantial knowledge, and among others. In this paper we present a comparison among CAs that make use of different evolutionary strategies; the first one implements a historical knowledge, the second one considers a circumstantial knowledge, and the third one implements a normative knowledge. These CAs are applied on a biobjective uncapacitated facility location problem (BOUFLP), the biobjective version of the well-known uncapacitated facility location problem. To the best of our knowledge, only few articles have applied evolutionary multiobjective algorithms on the BOUFLP and none of those has focused on the impact of the evolutionary strategy on the algorithm performance. Our biobjective cultural algorithm, called BOCA, obtains important improvements when compared to other well-known evolutionary biobjective optimisation algorithms such as PAES and NSGA-II. The conflicting objective functions considered in this study are cost minimisation and coverage maximisation. Solutions obtained by each algorithm are compared using a hypervolume S metric.
Design of Information System for Milking Dairy Cattle and Detection of Mastitis
Authors: Chen Ming-Chih , Chen Chien-Hsing , Siang Chong-Yu
Published: August 2014

A novel information system for detecting mastitis in dairy cattle and managing their milking processes in the milking parlor is designed. The system comprises three major subsystems—the mastitis detection device, the information display device, and the cloud database. The mastitis detection device can detect and evaluate the degree of mastitis immediately before the milking operations are carried out. The information display device shows information on the health of the dairy cattle obtained from a cloud database to manage the milk production of a dairy farm. Importantly, the proposed system utilizes a wireless sensor network (WSN) with low power consumption that connects the information display device with the remote management system. Experimental results reveal that our proposed system can reduce the risk of milking cattle with mastitis and improve efficiency of milk production.
The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma
Authors: Wang Haitao , Wang Rikang , Thrimawithana Thilini , Little Peter J. , Xu Jiangping , Feng Zhong-Ping , Zheng Wenhua
Published: August 2014

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC’s survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.
Synthesis, Crystal Structure, and Biological Activity ofcis/transAmide Rotomers of (Z)-N′-(2-Oxoindolin-3-ylidene)formohydrazide
Authors: Abdel-Aziz Hatem A. , Ghabbour Hazem A. , Eldehna Wagdy M. , Qabeel Maha M. , Fun Hoong-Kun
Published: September 2014

(Z)-N′-(2-Oxoindolin-3-ylidene)formohydrazide (2) was synthesized by the reaction of (Z)-3-hydrazonoindolin-2-one (1) with formic acid under reflux. The structure of2was characterized by IR, Mass,1H NMR, and X-ray crystal structure determination. Interestingly, compound2appeared in DMSO-d6ascisandtransamide rotomers in 25% and 75%, respectively. The X-ray analysis showed theZgeometrical isomer of2around –C=N– forcisandtransamide rotomers. The crystal of2belongs to monoclinic, space groupP21/c, witha=4.5206(1) Å,b=22.4747(7) Å,c=17.3637(5) Å,β=103.752(1)°,Z=8,V=1713.57(8) Å3,Dc=1.467 Mg m−3,μ=0.11 mm−1,F(000)=784,R=0.047, andwR=0.123for 3798 observed reflections withI>2σ(I). Compound2exhibited a moderate activity in its antimicrobial evaluation againstE. coliandP. aeruginosaand a good activity againstS. aureusclose to that of the standard drug ciprofloxacin. Thein vitroanticancer activity of2was evaluated against two human tumor cell lines, namely, HepG2 hepatocellular carcinoma and MCF-7 breast cancer. HepG2 cancer cell line was more susceptible to compound2than MCF-7.
Uniform Exponential Stability of Discrete Evolution Families on Space ofp-Periodic Sequences
Authors: Wang Yongfang , Zada Akbar , Ahmad Nisar , Lassoued Dhaou , Li Tongxing
Published: August 2014

We prove that the discrete systemζn+1=Anζnis uniformly exponentially stable if and only if the unique solution of the Cauchy problemζn+1=Anζn+eiθn+1zn+1, n∈Z+,ζ0=0,is bounded for any real numberθand anyp-periodic sequencez(n)withz(0)=0. Here,Anis a sequence of bounded linear operators on Banach spaceX.
System Efficiency of a Tap Transformer Based Grid Connection Topology Applied on a Direct Driven Generator for Wind Power
Authors: Apelfröjd Senad , Eriksson Sandra
Published: August 2014

Results from experiments on a tap transformer based grid connection system for a variable speed vertical axis wind turbine are presented. The tap transformer based system topology consists of a passive diode rectifier, DC-link, IGBT inverter, LCL-filter, and tap transformer. Full range variable speed operation is enabled by using the different step-up ratios of a tap transformer. Simulations using MATLAB/Simulink have been performed in order to study the behavior of the system. A full experimental set up of the system has been used in the laboratory study, where a clone of the on-site generator was driven by an induction motor and the system was connected to a resistive load to better evaluate the performance. Furthermore, the system is run and evaluated for realistic wind speeds and variable speed operation. For a more complete picture of the system performance, a case study using real site Weibull parameters is done, comparing different tap selection options. The results show high system efficiency at nominal power and an increase in overall power output for full tap operation in comparison with the base case, a standard transformer. In addition, the loss distribution at different wind speeds is shown, which highlights the dominant losses at low and high wind speeds. Finally, means for further increasing the overall system efficiency are proposed.
Marked Antigiardial Activity ofYucca baccataExtracts: A Potential Natural Alternative for Treating Protozoan Infections
Authors: Quihui-Cota Luis , León-Trujillo Rocio , Astiazarán-García Humberto , Esparza-Romero Julián , Robles María del Refugio , Robles-Zepeda Ramón E. , Canett Rafael , Sánchez-Escalante Jesús
Published: August 2014

Human Giardiosis is a public health problem in Mexico, where the national prevalence was estimated to be up to 68%. Misuse of antiprotozoal drugs may result in low effectiveness and undesirable side effects. Research on natural products is a good strategy for discovering more effective antiparasitic compounds. This study evaluated the antigiardial activity of extracts ofYucca baccata, which is native to northwestern Mexico. Forty-two gerbils (females) were weighed and orally inoculated with5×106Giardiatrophozoites. Two gerbils were selected at random to confirm infection. Forty living gerbils were randomly allocated into 5 treatment groups (8 per group). Gerbils were randomly assigned to be treated with 24.4 mg/mL, 12.2 mg/mL, and 6.1 mg/mL of extracts, metronidazole (2 mg/mL) or PBS, which were intragastrically administered once per day for 3 days. Nine gerbils died during the study course. On day 10 postinfection, gerbils were euthanized and trophozoites were quantified.Yuccaextracts reduced, albeit not significantly, the trophozoite counts in the duodenum segment. Only the high-extract concentration significantly reduced the trophozoite counts in the proximal segment and it was similar to that of metronidazole. Extracts ofY. baccatamay represent an effective and natural therapeutic alternative for human giardiosis.
Nonuniform Video Size Reduction for Moving Objects
Authors: Le Anh Vu , Jung Seung-Won , Won Chee Sun
Published: August 2014

Moving objects of interest (MOOIs) in surveillance videos are detected and encapsulated by bounding boxes. Since moving objects are defined by temporal activities through the consecutive video frames, it is necessary to examine a group of frames (GoF) to detect the moving objects. To do that, the traces of moving objects in the GoF are quantified by forming a spatiotemporal gradient map (STGM) through the GoF. Each pixel value in the STGM corresponds to the maximum temporal gradient of the spatial gradients at the same pixel location for all frames in the GoF. Therefore, the STGM highlights boundaries of the MOOI in the GoF and the optimal bounding box encapsulating the MOOI can be determined as the local areas with the peak average STGM energy. Once an MOOI and its bounding box are identified, the inside and outside of it can be treated differently for object-aware size reduction. Our optimal encapsulation method for the MOOI in the surveillance videos makes it possible to recognize the moving objects even after the low bitrate video compressions.
Hopf Bifurcation and Stability of Periodic Solutions for Delay Differential Model of HIV Infection of CD4+T-cells
Authors: Balasubramaniam P. , Prakash M. , Rihan Fathalla A. , Lakshmanan S.
Published: August 2014

This paper deals with stability and Hopf bifurcation analyses of a mathematical model of HIV infection ofCD4+T-cells. The model is based on a system of delay differential equations with logistic growth term and antiretroviral treatment with a discrete time delay, which plays a main role in changing the stability of each steady state. By fixing the time delay as a bifurcation parameter, we get a limit cycle bifurcation about the infected steady state. We study the effect of the time delay on the stability of the endemically infected equilibrium. We derive explicit formulae to determine the stability and direction of the limit cycles by using center manifold theory and normal form method. Numerical simulations are presented to illustrate the results.
Dust Identification over Arid and Semiarid Regions of Asia Using AIRS Thermal Infrared Channels
Authors: Xu Hui , Cheng Tianhai , Xie Donghai , Li Jiaguo , Wu Yu , Chen Hao
Published: August 2014

Asia dust generated in northern China exerts significant influences on regional air quality, weather, and climate. In this study, a dust identification algorithm over arid and semiarid regions of Asia was proposed based on the thermal observations of atmospheric infrared sounder (AIRS). Firstly, a combination of the line-by-line (LBL) and discrete ordinates radiative transfer (DISORT) model was utilized to investigate the thermal infrared signatures of dust and cloud in 800–1250 cm−1region. Secondly, six channels in the thermal infrared region were selected from AIRS to monitor dust from space, and a further sensitivity analysis for dust and cloud under different conditions was also performed. Then, the description of the detailed identification method was provided based on distinct thermal infrared signature of dust. At last, several dust events that observed in northern China between the period of 2008 and 2012 were analyzed, and the usefulness of monitoring the outbreaks of Asian dust was emphasized through the comparison with moderate resolution imaging spectroradiometer (MODIS) visible observations and cloud aerosol lidar with orthogonal polarization (CALIOP) data in this study.
Characteristics and Determinants of Partial Remission in Children with Type 1 Diabetes Using the Insulin-Dose-Adjusted A1C Definition
Authors: Pecheur Aurore , Barrea Thierry , Vandooren Valérie , Beauloye Véronique , Robert Annie , Lysy Philippe A.
Published: August 2014

To evaluate the characteristics and determinants of partial remission (PR) in Belgian children with type 1 diabetes (T1D), we analyzed records of 242 children from our center. Clinical and biological features were collected at diagnosis and during follow-up. PR was defined using the insulin-dose-adjusted A1C definition. PR occurred in 56.2% of patients and lasted 9.2 months (0.5 to 56.6). 25.6% of patients entered T1D with DKA, which correlated with lower PR incidence (17.6% versus 82.3% when no DKA). In our population, lower A1C levels at diagnosis were associated with higher PR incidence and in young children (0–4 years) initial A1C levels negatively correlated with longer PR. Early A1C levels were predictive of PR duration since 34% of patients had long PRs (>1 year) when A1C levels were ≤6% after 3 months whereas incidence of long PR decreased with higher A1Cs. C-peptide levels were higher in patients entering PR and remained higher until 3 years after diagnosis. Initial antibody titers did not influence PR except for anti-IA2 titers that correlated with A1C levels after 2 years. Presence of 2 versus 1 anti-islet antibodies correlated with shorter PR. PR duration did not influence occurrence of severe hypoglycemia or diabetes-related complications but was associated with lower A1C levels after 18 months. We show that, at diagnosis of T1D, parameters associated withβ-cell mass reserve (A1C, C-peptide, and DKA) correlate with the occurrence of PR, which affects post-PR A1C levels. Further research is needed to determine the long-term significance of PR.
Development and Analysis of Double‐Faced Radial and Cluster‐Arranged CMP Diamond Disk
Authors: Tsai M. Y. , Chen C. H. , Chiang J. H. , Yeh T. S.
Published: August 2014

In semiconductor manufacturing, diamond disks are indispensable for dressing chemical mechanical polishing (CMP) pads. Recently, 450 mm (18 inch) diameter wafers have been used to improve output and reduce wafer production cost. To polish 450 mm diameter wafers, the diameter of polishing pads must be increased to 1050 mm. In particular, because diamond disks are limited to 100 mm diameters, a much greater number of working crystals will be required for dressing a 1050 mm diameter pad. Consequently, new diamond disks must be developed. In this study, novel arrangements are made using a braze in diamond patterns, which are radial with a cluster arrangement of 3‐4 grits per cluster. Furthermore, a double‐faced combined diamond disk is developed. The polishing pad surface was characterized, and the effect of different diamond conditioners on wafer removal rate was studied. This research aims to develop a more suitable diamond disk for dressing 1050 mm diameter polishing pads.
Spatiotemporal Variations of Reference Crop Evapotranspiration in Northern Xinjiang, China
Authors: Wang Jian , Lv Xin , Wang Jiang-li , Lin Hai-rong
Published: August 2014

To set up a reasonable crop irrigation system in the context of global climate change in Northern Xinjiang, China, reference crop evapotranspiration (ET0) was analyzed by means of spatiotemporal variations. The ET0values from 1962 to 2010 were calculated by Penman-Monteith formula, based on meteorological data of 22 meteorological observation stations in the study area. The spatiotemporal variations of ET0were analyzed by Mann-Kendall test, Morlet wavelet analysis, and ArcGIS spatial analysis. The results showed that regional average ET0had a decreasing trend and there was an abrupt change around 1983. The trend of regional average ET0had a primary period about 28 years, in which there were five alternating stages (high-low-high-low-high). From the standpoint of spatial scale, ET0gradually increased from the northeast and southwest toward the middle; the southeast and west had slightly greater variation, with significant regional differences. From April to October, the ET0distribution significantly influenced the distribution characteristic of annual ET0. Among them sunshine hours and wind speed were two of principal climate factors affecting ET0.
Antenatal Care Strengthening in Jimma, Ethiopia: A Mixed-Method Needs Assessment
Authors: Villadsen Sarah Fredsted , Tersbøl Britt Pinkowski , Negussie Dereje , GebreMariam Abebe , Tilahun Abebech , Friis Henrik , Rasch Vibeke
Published: August 2014

Objective.We assessed how health system priorities matched user expectations and what the needs for antenatal care (ANC) strengthening were for improved maternal health in Jimma, Ethiopia.Methods.A questionnaire survey among all recent mothers in the study area was conducted to study the content of ANC and to identify the predictors of low ANC satisfaction. Further, a qualitative approach was applied to understand perceptions, practices, and policies of ANC.Results.There were no national guidelines for ANC in Ethiopia. Within the health system, the teaching of health professional students was given high priority, and that contributed to a lack of continuity and privacy. To the women, poor user-provider interaction was a serious concern hindering the trust in the health care providers. Further, the care provision was compromised by the inadequate laboratory facilities, unstructured health education, and lack of training of health professionals.Conclusions.Health system trials are needed to study the feasibility of ANC strengthening in the study area. Nationally and internationally, the leadership needs to be strengthened with supportive supervision geared towards building trust and mutual respect to protect maternal and infant health.
Endovascular Recanalization for Chronic Symptomatic Intracranial Vertebral Artery Total Occlusion
Authors: Xu Ziqi , Ma Ning , Mo Dapeng , Wong Edward Ho chung , Gao Feng , Jiao Liqun , Miao Zhongrong
Published: September 2014

Purpose.The outcome of recanalization in patients with chronic symptomatic intracranial vertebral artery (ICVA) total occlusion is poor. This paper reports the technical feasibility and long-term outcome of ICVA stenting in patients with chronic symptomatic total occlusion.Methods.Retrospective review of our prospectively maintained intracranial intervention database to identify patients with symptomatic total occlusion of ICVA with revascularization attempted >1 month after index ischemic event.Results.Eight patients (mean age 58 years) were identified. One had stroke and 7 had recurrent transient ischemic attacks. Four had bilateral ICVA total occlusion and 4 had unilateral ICVA total occlusion with severe stenosis contralaterally. Seven of 8 patients underwent endovascular recanalization, which was achieved in 6. Periprocedural complications included cerebellum hemorrhage, arterial dissection, perforation, and subacute in-stent thrombosis which occurred in 3 patients. One patient died of cerebellum hemorrhage. The other patients improved clinically after endovascular therapy.Conclusions.Stent-supported recanalization of ICVA total occlusion is technically feasible, and may become a viable treatment option in selected patients.
Vitamin D and Its Role as a Protective Factor in Allergy
Authors: Hoxha Mehmet , Zoto Maria , Deda Leonard , Vyshka Gentian
Published: August 2014

The relationship between vitamin D status and asthma has been subject to several studies in the last decade. Epidemiological data suggest that incidence of asthma and atopic diseases increased significantly in most Westernized countries. The significant variation between countries suggests that besides genetic factors, environmental aspects play a role in the pathogenesis of atopy. The prevalence of hypovitaminosis D is high in many industrialized countries. In addition to its relationship with bone metabolism, vitamin D is recognized as an immunomodulator, with important effects on both adaptive and innate immunity. Correlations between vitamin D status and asthma have been formulated, with a considerable interest in assessing whether this vitamin protects against or reduces asthma morbidity. In this review, we discuss recent findings regarding vitamin D status throughout Europe and its influence over asthma and allergic rhinitis prevalence. Geographical latitude and dietary habits may explain the lower prevalence of allergic disease in Albania. We also consider the effects of vitamin D supplementation in allergic disease. Several clinical trials are under way and their results are needed in order to make definitive recommendations about the optimal dose of vitamin D for prevention and treatment of asthma and allergic disease.
Evaluation of Analgesic Activity of the Methanol Extract from the Galls of Quercus infectoria (Olivier) in Rats
Authors: Fan Sook-Ha , Ali Noraisah Akbar , Basri Dayang Fredalina
Published: August 2014

The present study aims to investigate the analgesic activity of the methanol extract of the galls of Quercus infectoria in rats using hot plate and tail‐flick methods. The extract was administered intraperitoneally at a dose of 20 mg/kg while morphine sulfate and sodium salicylate (10 mg/kg) served as standards. The methanol extract exhibited significant analgesic activity in the tail‐flick model (P < 0.05) by increasing the reaction time of the rats to 8.0 sec at 30 min after treatment in comparison to control (4.4 sec). Morphine sulfate produced a reaction time of 11.9 sec in the same test. At the peak of activity (30 min), the extract produced maximum possible analgesia (MPA) of 34.2%, whilst morphine sulfate achieved a peak MPA of 70.9%. No analgesic effects have been observed using sodium salicylate in the tail‐flick model. In the same model, the extract and sodium salicylate demonstrated comparable reaction times. Tail‐flick is a better method to evaluate analgesic activity as no significant results were observed for all treatments using hot plate with the exception of morphine sulfate, which showed significant results only at 45 and 60 min after treatment. In conclusion, the methanol extract of the galls of Quercus infectoria displayed analgesic activity.
Acute Nontraumatic Clavicle Fracture Associated with Long-Term Bisphosphonate Therapy
Authors: Vun Shen Hwa , Husami Yahya , Shareef Sajan , Bramley Diane
Published: August 2014

Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third), tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of critical evaluation of patients with atypical fractures during long-term bisphosphonate therapy.
Molecular Pathways: The PERKs and Pitfalls of Targeting the Unfolded Protein Response in Cancer
Authors: Maas Nancy L. , Diehl J. Alan
Published: September 2014

The endoplasmic reticulum (ER) is a highly specialized organelle that provides an oxidizing, profolding environment for protein synthesis and maturation. The ER also hosts a dynamic signaling network that can sense and respond to physiologic changes that affect its environment, thereby influencing overall cell fate. Limitation of nutrients and oxygen have a direct effect on the efficiency of protein folding in the ER, and are classic inducers of the ER resident signaling pathway, the unfolded protein response (UPR). Not only does the UPR regulate ER homeostasis in normal cells experiencing such stress, but strong evidence also suggests that tumor cells can co-opt the cytoprotective aspects of this response to survive the hypoxic, nutrient-restricted conditions of the tumor microenvironment. Clin Cancer Res; 21(4); 675–9. ©2014 AACR.
Deferasirox limits cartilage damage following haemarthrosis in haemophilic mice
Authors: Roosendaal Goris , Mastbergen Simon , Coeleveld Katja , Biesma Douwe , Lafeber Floris , Schutgens Roger , Nieuwenhuizen Laurens
Published: September 2014

Joint bleeds in haemophilia result in iron-mediated synovitis and cartilage damage. It was evaluated whether deferasirox, an iron chelator, was able to limit the development of haemophilic synovitis and cartilage damage. Haemophilic mice were randomly assigned to oral treatment with deferasirox (30 mg/kg) or its vehicle (control) (30 mg/kg). Eight weeks after start of treatment, haemarthrosis was induced. After another five weeks of treatment, blood-induced synovitis and cartilage damage were determined. Treatment with deferasirox resulted in a statistically significant (p< 0.01) decrease in plasma ferritin levels as compared to the control group (823 ng/ml ± 56 and 1220 ng/ml ±114, respectively). Signs of haemophilic synovitis, as assessed by the Valentino score [range 0 (normal) – 10 (most affected)], were not different (p=0.52) when comparing the control group with the deferasirox group. However, deferasirox treatment resulted in a statistically significant (p< 0.01) reduction in cartilage damage, as assessed by the loss in Safranin O staining [range 0 (normal) – 6 (most affected)], when comparing the deferasirox group with the control group: score 2 (65.4 % vs 4.2 %), score 3 (26.9 % vs 4.2 %), score 4 (7.7 % vs 20.8 %), score 5 (0 % vs 54.2 %), and score 6 (0 % vs 16.7 %). Treatment with deferasirox limits cartilage damage following the induction of a haemarthrosis in haemophilic mice. This study demonstrates the role of iron in blood-induced cartilage damage. Moreover, these data indicate that iron chelation may be a potential prevention option to limit the development of haemophilic arthropathy.
Novel α-Actinin 2 Variant Associated With Familial Hypertrophic Cardiomyopathy and Juvenile Atrial Arrhythmias
Authors: Girolami Francesca , Iascone Maria , Tomberli Benedetta , Bardi Sara , Benelli Matteo , Marseglia Giuseppina , Pescucci Chiara , Pezzoli Laura , Sana Maria Elena , Basso Cristina , Marziliano Nicola , Merlini Piera Angelica , Fornaro Alessandra , Cecchi Franco , Torricelli Francesca , Olivotto Iacopo
Published: August 2014

Background—

Next-generation sequencing might be particularly advantageous in genetically heterogeneous conditions, such as hypertrophic cardiomyopathy (HCM), in which a considerable proportion of patients remain undiagnosed after Sanger. In this study, we present an Italian family with atypical HCM in which a novel disease-causing variant in α-actinin 2 (ACTN2) was identified by next-generation sequencing.

Methods and Results—

A large family spanning 4 generations was examined, exhibiting an autosomal dominant cardiomyopathic trait comprising a variable spectrum of (1) midapical HCM with restrictive evolution with marked biatrial dilatation, (2) early-onset atrial fibrillation and atrioventricular block, and (3) left ventricular noncompaction. In the proband, 48 disease genes for HCM, selected on the basis of published reports, were analyzed by targeted resequencing with a customized enrichment system. After bioinformatics analysis, 4 likely pathogenic variants were identified: TTN c.21977G>A (p.Arg7326Gln); TTN c.8749A>C (p.Thr2917Pro); ACTN2 c.683T>C (p.Met228Thr); and OBSCN c.13475T>G (p.Leu4492Arg). The novel variant ACTN2 c.683T>C (p.Met228Thr), located in the actin-binding domain, proved to be the only mutation fully cosegregating with the cardiomyopathic trait in 18 additional family members (of whom 11 clinically affected). ACTN2 c.683T>C (p.Met228Thr) was absent in 570 alleles of healthy controls and in 1000 Genomes Project and was labeled as Damaging by in silico analysis using polymorphism phenotyping v2, as Deleterious by sorts intolerant from tolerant, and as Disease-Causing by Mutation Taster.

Conclusions—

A targeted next-generation sequencing approach allowed the identification of a novel ACTN2 variant associated with midapical HCM and juvenile onset of atrial fibrillation, emphasizing the potential of such approach in HCM diagnostic screening.
Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure
Authors: Andersen Kasper , Mariosa Daniela , Adami Hans-Olov , Held Claes , Ingelsson Erik , Lagerros Ylva Trolle , Nyrén Olof , Ye Weimin , Bellocco Rino , Sundström Johan
Published: September 2014

Background—

The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

Methods and Results—

In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

Conclusions—

Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.
Development and Validation of a Short Version of the Seattle Angina Questionnaire
Authors: Chan Paul S. , Jones Philip G. , Arnold Suzanne A. , Spertus John A.
Published: September 2014

Background—

Clinical trials and national performance measures increasingly mandate reporting patients’ perspectives of their health status: their symptoms, function, and quality of life. Although the Seattle Angina Questionnaire (SAQ) is a validated disease-specific health status instrument for coronary artery disease (CAD) with high test–retest reliability, predictive power, and responsiveness, its use in routine clinical practice has been limited, in part, by its length (19 items).

Methods and Results—

Using data from 10 408 patients with CAD from 5 multicenter registries, we derived and validated a shortened version of the SAQ (SAQ-7) among patients presenting with stable CAD, undergoing percutaneous coronary intervention, and after acute myocardial infarction. We examined the psychometric properties of the SAQ-7 as compared with the full SAQ. Seven items from the Physical Limitation, Angina Frequency, and Quality of Life domains were identified for the SAQ-7, with high levels of concordance (0.88–1.00) with each original SAQ domain. The SAQ-7 demonstrated good construct validity (compared with Canadian Cardiovascular Society class for angina), with a correlation of 0.62 and 0.38 for patients with stable CAD and undergoing percutaneous coronary intervention, respectively. It was highly reproducible in patients with stable CAD (intraclass correlation, ≥0.78) and exhibited excellent responsiveness in patients after percutaneous coronary intervention (≥18 points in each SAQ domain). Finally, the SAQ-7 was predictive of 1-year mortality and readmission.

Conclusions—

To increase the feasibility of measuring patient-reported outcomes in patients with CAD, we developed and validated a shortened 7-item SAQ instrument for use in clinical trials and routine care.
Bcl10 Mediates Angiotensin II–Induced Cardiac Damage and Electrical Remodeling
Authors: Markó Lajos , Henke Norbert , Park Joon-Keun , Spallek Bastian , Qadri Fatimunnisa , Balogh András , Apel Ingrid J. , Oravecz-Wilson Katherine I. , Choi Mira , Przybyl Lukasz , Binger Katrina J. , Haase Nadine , Wilck Nicola , Heuser Arnd , Fokuhl Verena , Ruland Jürgen , Lucas Peter C. , McAllister-Lucas Linda M. , Luft Friedrich C. , Dechend Ralf , Müller Dominik N.
Published: September 2014

Angiotensin (Ang) II is a potent mediator of both hypertension and cardiac damage; however, the mechanisms by which this occur remain unclear. B-cell lymphoma/leukemia 10 (Bcl10) is a member of the CBM signalosome, which links Ang II and nuclear factor-κB signaling. We hypothesized that Bcl10 is pivotal in the pathogenesis of Ang II–induced cardiac damage. Ang II infusion in mice lacking Bcl10 resulted in reduced cardiac fibrosis, less cellular infiltration, and improved arrhythmogenic electric remodeling, despite a similar degree of hypertension or cardiac hypertrophy. Adoptive transfer of bone marrow (BM), whereby Bcl10 knockout or wildtype BM was transferred to their opposite genotype recipients, revealed the dual importance of Bcl10 within both cardiac and immune cells. Loss of Bcl10 in cardiac cells resulted in reduced expression of genes important for the adhesion and recruitment of immune cells. In vitro experiments demonstrated that adhesion of monocytes to Ang II–treated endothelial cells also required Bcl10. Additionally, Bcl10 deficiency in macrophages reduced their intrinsic migratory ability. To address the role of BM-derived fibroblasts in the formation of cardiac fibrosis, we explored whether Bcl10 is also important for the infiltration of BM-derived (myo)fibroblasts into the heart. The transfer of green fluorescent protein positive wildtype BM into Bcl10 knockout recipient mice revealed a reduced number of noncardiac (myo)fibroblasts compared with those wildtype recipients. Our results demonstrate the significant role of Bcl10 in multiple cell types important for the generation of Ang II–induced cardiac damage and electric remodeling and may provide a new avenue for therapeutic intervention.
Long-Term Outcomes After Combined Revascularization Surgery in Adult Moyamoya Disease
Authors: Cho Won-Sang , Kim Jeong Eun , Kim Chang Hyeun , Ban Seung Pil , Kang Hyun-Seung , Son Young Je , Bang Jae Seung , Sohn Chul-Ho , Paeng Jin Chul , Oh Chang Wan
Published: September 2014

Background and Purpose—

The surgical outcomes of adult moyamoya disease are rarely reported. We aimed to evaluate the long-term outcomes of combined revascularization surgery in patients with adult moyamoya disease.

Methods—

Combined revascularization surgery consisting of superficial temporal artery–middle cerebral artery anastomosis with encephalodurogaleosynangiosis was performed on 77 hemispheres in 60 patients. Clinical, angiographic, and hemodynamic states were evaluated retrospectively using quantitative methods preoperatively and postoperatively in the short-term (≈6 months) and long-term (≈5 years) periods. The mean clinical follow-up duration was 71.0±10.1 months (range, 60–104 months).

Results—

Clinical status improved until 6 months after surgery and remained stable thereafter, as assessed by the Karnofsky Performance Scale and modified Rankin Scale. The revascularization area relative to supratentorial area significantly increased in the long-term period compared with that in the short-term period (54.8% versus 44.2%;
P
<0.001). Cerebral blood flow in the territory of the middle cerebral artery improved in the short-term period compared with that in the preoperative period (68.7 versus 59.1; considering blood flow of the pons as 50;
P
<0.001) and thereafter became stable (65.5 in the long term;
P
=0.219). The annual risks of symptomatic hemorrhage and infarction were 0.4% and 0.2%, respectively, in the operated hemispheres.

Conclusions—

Combined revascularization surgery resulted in satisfactory long-term improvement in clinical, angiographic, and hemodynamic states and prevention of recurrent stroke.
Six new species of Saussurea (Asteraceae) from eastern Himalaya
Authors: Chen Yousheng
Published: September 2014

Six new species of Saussurea (Asteraceae, Cardueae) from eastern Himalaya, namely S. austrotibetica, S. bhutanensis, S. langpoensis, S. lhozhagensis, S. lhunzensis, and S. pagriensis are described and illustrated.
Busted ghosts: Rediscovery of supposedly destroyed types of Brazilian Mimosa (Leguminosae, Mimosoideae)
Authors: Borges Leonardo Maurici , Pirani José Rubens
Published: September 2014

In his monograph for neotropical Mimosa, Rupert Barneby made seemingly effective lectotypifications for a few binomials originally published by Taubert. He chose specimens in the Berlin herbarium (B), which he supposed had been destroyed. We hereby bring new evidence for the absence of these specimens in Berlin, their being in Hamburg (HBG) instead, and we designate them as lectotypes for the names in question.
Haslea sigma (Naviculaceae, Bacillariophyta) a new sigmoid benthic species from salt marshes of Southern Brazil
Authors: Talgatti Dávia , Sar Eugenia , Torgan Lezilda Carvalho
Published: September 2014

A new sigmoid diatom species Haslea sigma sp. nov. was found alive in sediment composed of clay and silt in salt marshes in Southern Brazil. The species is morphologically distinctive by the following combination of characters: 1) sigmoid valve, 2) thickened virgae forming a pseudostauros, 3) central raphe fissures almost straight and 4) terminal raphe fissures slightly curved. It was analyzed in light and electron microscopy and compared with the sigmoid Haslea nipkowii and with other spindle-shaped Haslea taxa possessing a pseudostauros.
Primulina jiangyongensis (Gesneriaceae), a new species from Southern Hunan, China
Authors: Li Ming , Yu Xun-Lin , Ma Qi-Xia
Published: September 2014

A new species, Primulina jiangyongensis (Gesneriaceae) from limestone areas in southern Hunan, China, is described and illustrated. The new species differs from other species of Primulina mainly by its yellow corolla, with the lower lip having several dark purple stripes, peduncle and bracts densely spreading villous, pedicel densely glandular-villous, and filaments dark purple. According to the IUCN Red List Criteria, P. jiangyongensis is assessed as Critically Endangered (CR B2a; C2b) because of its limited populations and vulnerable habitat.