bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modified Artificial Bee Colony Algorithm forp-Center Problems
Authors: Yurtkuran Alkın , Emel Erdal
Published: January 2014

The objective of thep-center problem is to locatep-centers on a network such that the maximum of the distances from each node to its nearest center is minimized. The artificial bee colony algorithm is a swarm-based meta-heuristic algorithm that mimics the foraging behavior of honey bee colonies. This study proposes a modified ABC algorithm that benefits from a variety of search strategies to balance exploration and exploitation. Moreover, random key-based coding schemes are used to solve thep-center problem effectively. The proposed algorithm is compared to state-of-the-art techniques using different benchmark problems, and computational results reveal that the proposed approach is very efficient.
From Pixels to Region: A Salient Region Detection Algorithm for Location‐Quantification Image
Authors: Zhang Mengmeng , Liu Zhi , Zhou Huan , Wang Jian
Published: January 2014

Image saliency detection has become increasingly important with the development of intelligent identification and machine vision technology. This process is essential for many image processing algorithms such as image retrieval, image segmentation, image recognition, and adaptive image compression. We propose a salient region detection algorithm for full‐resolution images. This algorithm analyzes the randomness and correlation of image pixels and pixel‐to‐region saliency computation mechanism. The algorithm first obtains points with more saliency probability by using the improved smallest univalue segment assimilating nucleus operator. It then reconstructs the entire saliency region detection by taking these points as reference and combining them with image spatial color distribution, as well as regional and global contrasts. The results for subjective and objective image saliency detection show that the proposed algorithm exhibits outstanding performance in terms of technology indices such as precision and recall rates.
The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients
Authors: An Gun Hee , Yun Jintak , Hong Yu Ah , Khvan Marina , Chung Byung Ha , Choi Bum Soon , Park Cheol Whee , Choi Yeong Jin , Kim Yong-Soo , Yang Chul Woo
Published: January 2014

The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ΔeGFR decreased significantly to0.4±1.7 mL·min−1·1.73 m−2per month 6 months after RIT compared to that observed 6 months before RIT (1.8±1.0,P<0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5±2.5versus7.0±3.5protein/creatinine (g/g),P<0.001). The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.
Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1
Authors: Beigh Mushtaq Ahmad , Showkat Mehvish , Bashir Basharat , Bashir Asma , Hussain Mahboob ul , Andrabi Khurshid Iqbal
Published: January 2014

Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation.
Heavy Metals in Water and Sediment: A Case Study of Tembi River
Authors: Shanbehzadeh Saeed , Vahid Dastjerdi Marzieh , Hassanzadeh Akbar , Kiyanizadeh Toba
Published: January 2014

This study was carried out to examine heavy metals concentration in water and sediment of upstream and downstream of the entry of the sewage to the Tembi River, Iran. Samples were collected from upstream and downstream and were analyzed for Cd, Cr, Cu, Fe, Pb, Ni, and Zn by atomic absorption spectrophotometer. The results indicated that the average concentration of the metals in water and sediment on downstream was more than that of upstream. The comparison of the mean concentrations of heavy metals in water of the Tembi River with drinking water standards and those in the water used for agriculture suggests that the mean concentration of Cu and Zn lies within the standard range for drinking water and the mean concentration of Mn, Zn, and Pb lies within the standard range of agricultural water. The highest average concentration on downstream for Pb in water and for Mn in sediment was 1.95 and 820.5 ppm, respectively. Also, the lowest average concentration on upstream was identified for Cd in water and sediment 0.07 and 10 ppm, respectively. With regard to the results, it gets clear that using the water for recreational purposes, washing, and fishing is detrimental to human health and the environment.
Efficacy and Cost-Efficacy of Biologic Therapies for Moderate to Severe Psoriasis: A Meta-Analysis and Cost-Efficacy Analysis Using the Intention-to-Treat Principle
Authors: Chi Ching-Chi , Wang Shu-Hui
Published: January 2014

Background. Compared to conventional therapies, biologics are more effective but expensive in treating psoriasis.Objective. To evaluate the efficacy and cost-efficacy of biologic therapies for psoriasis.Methods. We conducted a meta-analysis to calculate the efficacy of etanercept, adalimumab, infliximab, and ustekinumab for at least 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) and Physician’s Global Assessment clear/minimal (PGA 0/1). The cost-efficacy was assessed by calculating the incremental cost-effectiveness ratio (ICER) per subject achieving PASI 75 and PGA 0/1.Results. The incremental efficacy regarding PASI 75 was 55% (95% confidence interval (95% CI) 38%–72%), 63% (95% CI 59%–67%), 71% (95% CI 67%–76%), 67% (95% CI 62%–73%), and 72% (95% CI 68%–75%) for etanercept, adalimumab, infliximab, and ustekinumab 45 mg and 90 mg, respectively. The corresponding 6-month ICER regarding PASI 75 was $32,643 (best case $24,936; worst case $47,246), $21,315 (best case $20,043; worst case $22,760), $27,782 (best case $25,954; worst case $29,440), $25,055 (best case $22,996; worst case $27,075), and $46,630 (best case $44,765; worst case $49,373), respectively. The results regarding PGA 0/1 were similar.Conclusions. Infliximab and ustekinumab 90 mg had the highest efficacy. Meanwhile, adalimumab had the best cost-efficacy, followed by ustekinumab 45 mg and infliximab.
Impact of Maternal Thyroperoxidase Status on Fetal Body and Brain Size
Authors: Wilson Roneé E. , Salihu Hamisu M. , Groer Maureen W. , Dagne Getachew , O’Rourke Kathleen , Mbah Alfred K.
Published: January 2014

The obstetric consequences of abnormal thyroid function during pregnancy have been established. Less understood is the influence of maternal thyroid autoantibodies on infant outcomes. The objective of this study was to examine the influence of maternal thyroperoxidase (TPO) status on fetal/infant brain and body growth. Six-hundred thirty-one (631) euthyroid pregnant women were recruited from prenatal clinics in Tampa Bay, Florida, and the surrounding area between November 2007 and December 2010. TPO status was determined during pregnancy and fetal/infant brain and body growth variables were assessed at delivery. Regression analysis revealed maternal that TPO positivity was significantly associated with smaller head circumference, reduced brain weight, and lower brain-to-body ratio among infants born to TPO+ white, non-Hispanic mothers only, distinguishing race/ethnicity as an effect modifier in the relationship. No significant differences were noted in body growth measurements among infants born to TPO positive mothers of any racial/ethnic group. Currently, TPO antibody status is not assessed as part of the standard prenatal care laboratory work-up, but findings from this study suggest that fetal brain growth may be impaired by TPO positivity among certain populations; therefore autoantibody screening among high-risk subgroups may be useful for clinicians to determine whether prenatal thyroid treatment is warranted.
Mechanical Characteristics of Hardened Concrete with Different Mineral Admixtures: A Review
Authors: Ayub Tehmina , Khan Sadaqat Ullah , Memon Fareed Ahmed
Published: January 2014

The available literature identifies that the addition of mineral admixture as partial replacement of cement improves the microstructure of the concrete (i.e., porosity and pore size distribution) as well as increasing the mechanical characteristics such as drying shrinkage and creep, compressive strength, tensile strength, flexural strength, and modulus of elasticity; however, no single document is available in which review and comparison of the influence of the addition of these mineral admixtures on the mechanical characteristics of the hardened pozzolanic concretes are presented. In this paper, based on the reported results in the literature, mechanical characteristics of hardened concrete partially containing mineral admixtures including fly ash (FA), silica fume (SF), ground granulated blast furnace slag (GGBS), metakaolin (MK), and rice husk ash (RHA) are discussed and it is concluded that the content and particle size of mineral admixture are the parameters which significantly influence the mechanical properties of concrete. All mineral admixtures enhance the mechanical properties of concrete except FA and GGBS which do not show a significant effect on the strength of concrete at 28 days; however, gain in strength at later ages is considerable. Moreover, the comparison of the mechanical characteristics of different pozzolanic concretes suggests that RHA and SF are competitive.
Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6
Authors: Malhi Saima Mahmood , Jawed Huma , Hanif Farina , Ashraf Nadeem , Zubair Farhat , Siddiqui Bina S. , Begum Sabira , Kabir Nurul , Simjee Shabana Usman
Published: January 2014

Brain-derived neurotrophic factor (BDNF) and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ-) induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg) was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n=12animals/group) is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P<0.003) and c-Fos (P<0.01) protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.
Studies on Optimization of Growth Parameters for L-Asparaginase Production byStreptomyces ginsengisoli
Authors: Deshpande Neelima , Choubey Prachi , Agashe Manasi
Published: January 2014

A species ofStreptomyces,Streptomyces ginsengisoli, a river isolate, was evaluated for production of an enzyme, L-asparaginase, with multiple functions mainly anticancer activity. The actinomycete was subjected to submerged fermentation by “shake flask” method. The quantity of L-asparaginase produced was estimated as 3.23 μmol/mL/min. The effect of various culture conditions on L-asparaginase production was studied by adopting a method of variation in one factor at a time. Of the various conditions tested, glucose (followed by starch) and peptone served as good carbon and nitrogen sources, respectively, for maximal production of enzyme at pH 8. The temperature of 30°C and an incubation period of 5 days with 0.05 g% asparagine concentration were found to be optimum for L-asparaginase production.
Bioconversion of Airborne Methylamine by Immobilized Recombinant Amine Oxidase from the Thermotolerant YeastHansenula polymorpha
Authors: Sigawi Sasi , Nisnevitch Marina , Zakalska Oksana , Zakalskiy Andriy , Nitzan Yeshayahu , Gonchar Mykhailo
Published: January 2014

Aliphatic amines, including methylamine, are air-pollutants, due to their intensive use in industry and the natural degradation of proteins, amino acids, and other nitrogen-containing compounds in biological samples. It is necessary to develop systems for removal of methylamine from the air, since airborne methylamine has a negative effect on human health. The primary amine oxidase (primary amine : oxygen oxidoreductase (deaminating) or amine oxidase, AMO; EC 1.4.3.21), a copper-containing enzyme from the thermotolerant yeastHansenula polymorphawhich was overexpressed in baker’s yeastSaccharomyces cerevisiae, was tested for its ability to oxidize airborne methylamine. A continuous fluidized bed bioreactor (CFBR) was designed to enable bioconversion of airborne methylamine by AMO immobilized in calcium alginate (CA) beads. The results demonstrated that the bioreactor with immobilized AMO eliminates nearly 97% of the airborne methylamine. However, the enzymatic activity of AMO causes formation of formaldehyde. A two-step bioconversion process was therefore proposed. In the first step, airborne methylamine was fed into a CFBR which contained immobilized AMO. In the second step, the gas flow was passed through another CFBR, with alcohol oxidase from the yeastH. polymorphaimmobilized in CA, in order to decompose the formaldehyde formed in the first step. The proposed system provided almost total elimination of the airborne methylamine and the formaldehyde.
A PSO-Based Hybrid Metaheuristic for Permutation Flowshop Scheduling Problems
Authors: Zhang Le , Wu Jinnan
Published: January 2014

This paper investigates the permutation flowshop scheduling problem (PFSP) with the objectives of minimizing the makespan and the total flowtime and proposes a hybrid metaheuristic based on the particle swarm optimization (PSO). To enhance the exploration ability of the hybrid metaheuristic, a simulated annealing hybrid with a stochastic variable neighborhood search is incorporated. To improve the search diversification of the hybrid metaheuristic, a solution replacement strategy based on the pathrelinking is presented to replace the particles that have been trapped in local optimum. Computational results on benchmark instances show that the proposed PSO-based hybrid metaheuristic is competitive with other powerful metaheuristics in the literature.
Impact of Molecular Testing in the Diagnosis of Thyroid Fine Needle Aspiration Cytology: Data from Mainland China
Authors: Guo Hui-qin , Zhao Huan , Zhang Zhi-hui , Zhu Yan-li , Xiao Ting , Pan Qin-jing
Published: January 2014

Background. The molecular work-up of thyroid nodules from fine needle aspiration samples has given clinicians a new level of diagnostic information. The aim of the present study was to evaluate the utility of molecular analysis in thyroid fine needle aspiration samples from a Chinese population.Methods. Specimens were collected from thyroid nodules by fine needle aspiration. Cytology diagnosis and genes analysis were performed and correlated with histology outcome.Results. A total of 83 patients with thyroid nodules were enrolled, including 20 benign lesions and 63 papillary carcinomas. BRAF and RAS mutations and RET/PTC gene rearrangements were found in 65.1%, 0%, and 1.6% of papillary carcinomas, respectively. No gene alterations were found in benign lesions. The combination of BRAF testing and cytology improved the accuracy of cytology from 69.9% to 89.2%(P<0.05). Moreover, BRAF testing confirmed 82.4% of papillary carcinomas with suspicious cytology and identified 33.3% of papillary carcinomas with atypia cytology.Conclusions. Of the three candidate markers, BRAF testing showed diagnostic utility in fine needle aspiration. Combining BRAF testing with cytology improves the accuracy of fine needle biopsy. Those who have positive BRAF and malignant or suspicious malignant cytology can undergo thyroidectomy without a frozen section.
Automated Generation of Traffic Incident Response Plan Based on Case-Based Reasoning and Bayesian Theory
Authors: Ma Yongfeng , Zhang Wenbo , Lu Jian , Yuan Li
Published: January 2014

Traffic incident response plan, specifying response agencies and their responsibilities, can guide responders to take actions effectively and timely after traffic incidents. With a reasonable and feasible traffic incident response plan, related agencies will save many losses, such as humans and wealth. In this paper, how to generate traffic incident response plan automatically and specially was solved. Firstly, a well-known and approved method, Case-Based Reasoning (CBR), was introduced. Based on CBR, a detailed case representation andR5-cycle of CBR were developed. To enhance the efficiency of case retrieval, which was an important procedure, Bayesian Theory was introduced. To measure the performance of the proposed method, 23 traffic incidents caused by traffic crashes were selected and three indicators, PrecisionP, RecallR, and IndicatorF, were used. Results showed that 20 of 23 cases could be retrieved effectively and accurately. The method is practicable and accurate to generate traffic incident response plans. The method will promote the intelligent generation and management of traffic incident response plans and also make Traffic Incident Management more scientific and effective.
Fuzzy Integral Equations and Strong Fuzzy Henstock Integrals
Authors: Shao Yabin , Zhang Huanhuan
Published: January 2014

By using the strong fuzzy Henstock integral and its controlled convergence theorem, we generalized the existence theorems of solution for initial problems of fuzzy discontinuous integral equation.
Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis
Authors: Hanyecz A. , Olasz K. , Tarjanyi O. , Nemeth P. , Mikecz K. , Glant T. T. , Boldizsar F.
Published: January 2014

Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.
Analysis of Questionnaire for Traditional Medicine and Development of Decision Support System
Authors: Katayama Kotoe , Yamaguchi Rui , Imoto Seiya , Watanabe Kenji , Miyano Satoru
Published: January 2014

Kampo medicine is the Japanese adaptation of traditional medicine. In Kampo medicine, “medical interview” plays an important role. “Medical interview” in Japanese traditional medicine includes not only chief complaint but also a questionnaire that asked about the patient′s lifestyle and subjective symptoms. The diagnosis by Kampo is called “Sho” and determined by completely different view from Western medicine. Specialists gather all available information and decide “Sho.” And this is the reason why non‐Kampo specialists without technical knowledge have difficulties to use traditional medicine. We analyzed “medical interview” data to establish an indicator for non‐Kampo specialist without technical knowledge to perform suitable traditional medicine. We predicted “Sho” by using random forests algorithm which is powerful algorithm for classification. First, we use all the 2830 first‐visit patients’ data. The discriminant ratio of training data was perfect but that of test data is only 67.0%. Second, to achieve high prediction power for practical use, we did data cleaning, and discriminant ratio of test data was 72.4%. Third, we added body mass index (BMI) data to “medical interview” data and discriminant ratio of test data is 91.2%. Originally, deficiency and excess category means that patient is strongly built or poorly built. We notice that the most important variable for classification is BMI.
IVIG Effects on Erythrocyte Sedimentation Rate in Children
Authors: Salehzadeh Farhad , Noshin Ahmadvand , Jahangiri Sepideh
Published: January 2014

Background. Erythrocyte sedimentation rate (ESR) is a valuable laboratory tool in evaluation of infectious, inflammatory, and malignant diseases. Red blood cells in outside from the body precipitate due to their higher density than the plasma. In this study we discuss the IVIG effect on ESR in different diseases and different ages.Methods and Materials. Fifty patients under 12 years old who had indication to receive IVIG enrolled in this study. Total dose of IVIG was 2 gr/kg (400 mg/kg in five days or 2 gr/kg in single dose). ESR before infusion of IVIG and within 24 hours after administration of the last dose of IVIG was checked.Results. 23 (46%) patients were males and 27 (54%) were females. The mean of ESR before IVIG was31.8±29.04and after IVIG it was47.2±36.9; this difference was meaningful(P=0.05). Results of ESR changes in different age groups, 6 patients less than 28 days, 13 patients from 1 month to 1 year, 20 patients from 1 to 6 years old, and 11 patients from 6 to 12 years have been meaningful (P=0.001,P=0.025, andP=0.006, resp.).Conclusion. In patients who are receiving IVIG as a therapy, ESR increased falsely (noninflammatory rising); therefore use of ESR for monitoring of response to treatment may be unreliable. Although these results do not apply to neonatal group, we suggest that, in patients who received IVIG, interpretation of ESR should be used cautiously on followup.
Pan-PIM Kinase Inhibition Provides a Novel Therapy for Treating Hematologic Cancers
Authors: Garcia Pablo D. , Langowski John L. , Wang Yingyun , Chen Min , Castillo Joseph , Fanton Christie , Ison Marjorie , Zavorotinskaya Tatiana , Dai Yumin , Lu Jing , Niu Xiao-Hong , Basham Stephen , Chan Julie , Yu Jianjun , Doyle Michael , Feucht Paul , Warne Robert , Narberes Jamie , Tsang Tiffany , Fritsch Christine , Kauffmann Audrey , Pfister Estelle , Drueckes Peter , Trappe Joerg , Wilson Christopher , Han Wooseok , Lan Jiong , Nishiguchi Gisele , Lindvall Mika , Bellamacina Cornelia , Aycinena J. Alex , Zang Richard , Holash Jocelyn , Burger Matthew T.
Published: January 2014

Purpose: PIM kinases have been shown to act as oncogenes in mice, with each family member being able to drive progression of hematologic cancers. Consistent with this, we found that PIMs are highly expressed in human hematologic cancers and show that each isoform has a distinct expression pattern among disease subtypes. This suggests that inhibitors of all three PIMs would be effective in treating multiple hematologic malignancies.

Experimental Design: Pan-PIM inhibitors have proven difficult to develop because PIM2 has a low Km for ATP and, thus, requires a very potent inhibitor to effectively block the kinase activity at the ATP levels in cells. We developed a potent and specific pan-PIM inhibitor, LGB321, which is active on PIM2 in the cellular context.

Results: LGB321 is active on PIM2-dependent multiple myeloma cell lines, where it inhibits proliferation, mTOR-C1 signaling and phosphorylation of BAD. Broad cancer cell line profiling of LGB321 demonstrates limited activity in cell lines derived from solid tumors. In contrast, significant activity in cell lines derived from diverse hematological lineages was observed, including acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), multiple myeloma and non-Hodgkin lymphoma (NHL). Furthermore, we demonstrate LGB321 activity in the KG-1 AML xenograft model, in which modulation of pharmacodynamics markers is predictive of efficacy. Finally, we demonstrate that LGB321 synergizes with cytarabine in this model.

Conclusions: We have developed a potent and selective pan-PIM inhibitor with single-agent antiproliferative activity and show that it synergizes with cytarabine in an AML xenograft model. Our results strongly support the development of Pan-PIM inhibitors to treat hematologic malignancies. Clin Cancer Res; 20(7); 1834–45. ©2014 AACR.
Associations between Vitamin D–Binding Protein Isotypes, Circulating 25(OH)D Levels, and Vitamin D Metabolite Uptake in Colon Cancer Cells
Authors: Hibler Elizabeth A. , Jacobs Elizabeth T. , Stone Angelika Dampf , Sardo Christine L. , Galligan Michael A. , Jurutka Peter W.
Published: January 2014

Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D–responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P < 0.01) compared with 1S_1S. Consistent with these in vivo observations, cellular data revealed that 25(OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P < 0.01). The 1F_1S and 1F_2 isotypes produced the greatest reporter gene induction with 1,25(OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention. Cancer Prev Res; 7(4); 426–34. ©2014 AACR.
Impact of HLA Antibodies on Graft Survival in Long-Term Renal Recipients with Functional Grafts
Authors: Zeng Yigang , Liu Zhihong , Liu Yong , Fan Yu , Guo Yifeng , Qiu Jianxin
Published: January 2014

Objectives: Accumulating evidence supports the hypothesis that HLA antibodies play an important role in early renal allograft injury. However, the effects of HLA antibodies on long-term graft survival are still poorly understood. In this study, we examined the impact of HLA antibodies on graft survival in long-term renal recipients with functional grafts for 10 years. Material and Methods: In this retrospective study, long-term renal recipients were defined as kidney transplant recipients who had normally functioning renal grafts (serum creatinine level <2.0 mg/dl) for 10 years. Posttransplant serum samples from a total of 92 long-term renal allograft recipients on cyclosporine-based triple maintenance drug therapy (121.6 ± 0.886 months) were screened for the specificities of anti-HLA antibodies. The results of HLA antibodies before the transplantation, assessed using the same test method, were compared with those after their transplantations. Moreover, these 92 patients who received cadaveric renal transplant between January 2000 and December 2002 were followed up for about 10 years (range 107-135 months). Results: 27 patients had HLA-I antibodies and 16 patients had HLA-II antibodies before the transplantation, whereas 12 patients had HLA-I antibodies and 18 patients had HLA-II antibodies after the transplantation. Moreover, the types of HLA antibodies were different from those found before the transplantation. In these renal recipients with functioning renal grafts, the estimated glomerular filtration rate was 66.52 ± 14.52 ml/min/1.73 m2 in the HLA antibody-positive group (n = 23) and 69.09 ± 25.54 ml/min/1.73 m2 negative in the HLA antibody-negative group (n = 69, p > 0.05). Three patients (3.26%) (3 out of 92) had donor-specific anti-HLA antibodies (DSA). The frequency of DSA in this study was lower than that in the general Chinese Han renal recipient population. Conclusions: We find that all HLA antibodies in the long-term renal grafts are newly formed after the transplantation. The HLA antibody status has little impact on the renal graft function in the long-term renal recipients.
Quantitative Light-Induced Fluorescence to Measure Enamel Remineralization in vitro
Authors: Gomez J. , Pretty I.A. , Santarpia III R.P. , Cantore B. , Rege A. , Petrou I. , Ellwood R.P.
Published: January 2014

The aim of this study was to compare the ability of quantitative light-induced fluorescence (QLF) and surface microhardness (SMH) to measure the remineralization of enamel subsurface lesions, using a pH-cycling model including treatment with 0-ppm, 550-ppm or 1,100-ppm sodium fluoride (NaF) dentifrices. Methods: Subsurface lesions were created in human enamel specimens (n = 36) and exposed to a remineralization pH-cycling model for 14 days. The pH-cycling model was performed in an automated system where specimens were subjected to a demineralizing solution for 20 min and treatment for 1 min and were then remineralized for 7 h 39 min, 3 times daily. The treatments consisted of 3 NaF, silica-containing dentifrices (0 ppm F; 550 ppm F; 1,100 ppm F). The outcome variables were: change from baseline in surface hardness and percentage change from baseline in fluorescence. An ANCOVA explored differences between different treatment groups (at the p < 0.05 level). Associations between QLF and SMH were evaluated using Spearman's correlation coefficient. Results: The percentage SMH changes were 14.9 ± 2.1%, 56.6 ± 9.6% and 103.9 ± 14.6% for the 0-, 550- and 1,100-ppm F dentifrices, respectively. The percentage fluorescence changes were 15.6 ± 7.1%, 59.8 ± 11.9% and 85 ± 13.2%, respectively. The differences between all pairwise comparisons were statistically significant for both methods (p = 0.001). QLF correlated with SMH (r = 0.67). Conclusions: Both the SMH and QLF methods demonstrated a significant F dose response for toothpaste in this in vitro remineralization model, and both methods were able to distinguish treatments with different F levels.
Polycystic Kidney Disease with Renal Calculi Treated by Percutaneous Nephrolithotomy: A Report of 11 Cases
Authors: Zhang Junhui , Zhang Jianzhong , Xing Nianzeng
Published: January 2014

Objective: To evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) in the treatment of congenital autosomal dominant polycystic kidney disease (ADPKD) with renal calculi. Methods: A total of 11 cases of ADPKD with renal calculi were retrospectively studied. All cases were treated by PCNL and clinical parameters such as age, sex, stone burden, operation time, blood loss, complications and perioperative serum creatinine levels were collected and analyzed. All patients were routinely followed up for 36 months postoperatively and the efficacy and safety of PCNL in the management of ADPKD with renal calculi were assessed. Results: All procedures were successful without conversion to open surgery. The mean stone burden was 3.4 ± 0.7 cm (range 2.5-4.6 cm). The overall stone clearance rate was 81.8% (9/11). Two patients received extracorporeal shock wave lithotripsy postoperatively because of residual calculi. The mean operation time was 77 ± 23.5 min (range 45-128 min) and the mean blood loss was 147 ± 56 ml (range 80-260 ml). The mean preoperative serum creatinine level was 15.13 ± 3.30 mg/dl (range 9.90-20.14 mg/dl) and the mean postoperative serum creatinine level was 14.28 ± 2.24 mg/dl (range 10.76-17.28 mg/dl). Four cases had fever postoperatively (36.4%). Three patients had hemorrhage and two patients received blood transfusion. No patient had peripheral viscera injury. Statistical comparison showed that PCNL had no impact on perioperative renal function (p > 0.05). Conclusions: In spite of anatomical deformation and impairment of renal function, PCNL is an effective and safe procedure in managing ADPKD with renal calculi.
Cariogenic Effects of Probiotic Lactobacillus rhamnosus GG in a Dental Biofilm Model
Authors: Schwendicke F. , Dörfer C. , Kneist S. , Meyer-Lueckel H. , Paris S.
Published: January 2014

Probiotic bacteria have been suggested to inhibit Streptococcus mutans (SM) and thus prevent dental caries. However, supporting evidence is weak and probiotic species might be cariogenic themselves. Thus, we compared and combined the probiotic Lactobacillus rhamnosus GG (LGG) with SM and analysed the resulting mineral loss (ΔZ) in dental tissues. We simulated three biofilm compositions (SM, LGG, SM × LGG), two lesion sites (smooth enamel, dentin cavity) and two nutrition supply frequencies (twice/day, 6 times/day) in a multi-station, continuous-culture biofilm model. A total of 240 bovine enamel and dentin samples were cut, polished and embedded. All experimental procedures were performed in independent duplicates, with 10 samples being allocated to each group for each experiment (final sample size n = 20/group). Biofilms were cultured on the specimens and supplied with 2% sucrose medium and artificial saliva in consecutive pulses. After 10 days, ΔZ and bacterial numbers were assessed. SM × LGG biofilms caused significantly increased ΔZ compared with SM or LGG biofilms (p < 0.01, Mann-Whitney test), and ΔZ was significantly increased in dentin cavities compared with smooth enamel lesions (p < 0.01). Bacterial numbers did not significantly differ between biofilms of different species (p > 0.05, ANOVA). Frequent nutrition supply significantly increased bacterial numbers (p < 0.01). Biofilms in dentin cavities compared to smooth enamel harboured significantly more bacteria (p < 0.05). LGG induced mineral loss especially in dentin cavities and under highly cariogenic conditions. LGG did not have inhibitory effects on SM, but rather contributed to the caries process in vitro.
Caries and ABO Secretor Status in a Hungarian Population of Children and Adolescents: An Exploratory Study
Authors: Kárpáti K. , Braunitzer G. , Toldi J. , Turzó K. , Virág K. , Reiche W.T. , Rakonczay Z. , Nagy K.
Published: January 2014

ABO blood group antigen (ABGA) secretion into the saliva and other body fluids is a well-known phenomenon, and there is evidence to suggest a link between secretor status and the appearance of caries. It has been proposed that secretion of these antigens into the saliva might be caries-preventive, however, this proposition is still a matter of debate. Our aim was to examine the relationship between caries experience and secretor status in a group of Hungarian children and adolescents in a cross-sectional study. Altogether 130 children and adolescents participated in the study (aged 6-18 years). Participants were divided into two groups according to dentition (i.e. mixed and permanent). ABGA were determined from saliva. The DMF-T and dmf-t (decayed, missing, and filled) indices were calculated, as well as the oral health hygiene index-simplified plaque index. Association of these indices with secretor status was examined. In mixed dentition, the mean dmf-t values were significantly lower in the secretor group (2.1 ± 0.52 SEM), as compared to the nonsecretor group (3.8 ± 0.93 SEM; p < 0.05, Mann-Whitney U test). The finding that children of mixed dentition are apparently better protected against caries suggests that the assumed protective effect might be associated with deciduous teeth, but given the general paucity of knowledge about this topic, further research is indicated.
Dengue Virus Serotype-2 Impairs Proliferation of Healthy Donors' T Lymphocytes
Authors: Fuentes-Miranda C.J. , Sánchez-García F.J. , Coker A.R. , Rojas-Espinosa O. , Salinas-Tobón R. , Moreno-Altamirano M.M.B.
Published: January 2014

Objectives: T lymphocytes are not infected by dengue virus (DENV), nevertheless it is possible that exposure to DENV may affect their function. T lymphocytes from DENV-infected individuals are impaired in their proliferative capacity, although this effect has been attributed to altered function of antigen-presenting cells rather than to an intrinsic defect on T lymphocytes. Here we analyzed whether T lymphocytes from healthy donors became impaired in their proliferative capacity following in vitro exposure to DENV serotype-2 (DENV-2), as well as the possible mechanisms for this. Methods: Isolated CD4+ and CD8+ T lymphocytes from healthy donors were in vitro exposed to DENV-2, before polyclonal activation, cell proliferation, IL-2 synthesis. IL-2Rα expression, nuclear translocation of NF-AT and NF-κB, and intracellular calcium flux were assessed. Results: In vitro exposure of both CD4+ and CD8+ T lymphocytes from healthy donors to DENV-2 impairs cell proliferation, IL-2 synthesis, and IL-2Rα (CD25) cell membrane expression. Signalling wise, exposure to DENV-2 impairs the nuclear translocation of NF-AT, downstream of intracellular calcium mobilization, as well as that of NF-κB. Conclusion: In the course of a dengue infection, direct exposure of T lymphocytes to DENV could affect cell-mediated immune responses.
The Incidence and Risk Factors of Infusion-Related Reactions to Rituximab for Treating B Cell Malignancies in a Single Tertiary Hospital
Authors: Jung Jae-Woo , Kang Hye-Ryun , Lee Se-Hoon , Cho Sang-Heon
Published: January 2014

Background: Rituximab is a chimeric anti-CD20 human/mouse monoclonal antibody. As its usage has increased, there have been growing concerns about rituximab-related infusion-related reactions (IRRs). Objective: The aim of this study is to verify the clinical features and risk factors of IRRs by rituximab, and to help establish clinical guidelines for their prevention. Methods: We reviewed electronic medical records of all the adult patients who were prescribed rituximab from January 2005 to July 2010 for B cell malignancy at Seoul National University Hospital. Results: A total of 389 cases of IRRs by rituximab (12.5% of a total of 3,104 infusions) were identified in 281 patients (49.4% of a total of 568 patients). IRRs most frequently occurred during the first infusion (40.5%) and abruptly decreased in subsequent infusions to rates of 3-8% (p < 0.001). The incidence of IRRs in patients premedicated with corticosteroid for their first infusion was significantly lower when compared to patients not pretreated with corticosteroid prior to rituximab infusion (8.3 vs. 41.2%, p = 0.017). Conclusion: Almost half of all patients in the study experienced IRRs at least once during their scheduled rituximab treatment. Premedication with corticosteroid can be recommended in patients with high risk of IRR in the first infusion.
Building an Ovary: Insights into Establishment of Somatic Cell Lineages in the Mouse
Authors: Nicol Barbara , Yao Humphrey H.-C.
Published: January 2014

The molecular pathways that drive the differentiation of somatic cell populations in the testis and ovary have been the subjects of intensive research over the past decade. It is now clear that ovarian differentiation is a coordinate event driven by secreted factors including R-spondin1, WNT4, and follistatin and transcriptional regulators such as β-catenin and FOXL2. These factors direct bipotential somatic cell lineages toward an ovarian fate and simultaneously suppress the emergence of testis-determining processes. This review summarizes the molecular pathways responsible for establishment of the ovary and discusses the current hypotheses on the origin(s) of somatic cell lineages and how these somatic cells acquire the characteristics necessary for their function during ovarian development and maintenance.
Appropriateness of Diagnostic Catheterization for Suspected Coronary Artery Disease in New York State
Authors: Hannan Edward L. , Samadashvili Zaza , Cozzens Kimberly , Walford Gary , Holmes David R. , Jacobs Alice K. , Stamato Nicholas J. , Venditti Ferdinand J. , Sharma Samin , King Spencer B.
Published: January 2014

Background—

Appropriate use criteria for diagnostic catheterization (DC) were recently published. These criteria are yet to be examined for a large population of patients undergoing DC.

Methods and Results—

New York State’s Cardiac Diagnostic Catheterization Database was used to identify patients undergoing DC for coronary artery disease between 2010 and 2011 for suspected coronary artery disease. Patients were rated by the appropriate use criteria as appropriate, uncertain, and inappropriate for DC. The relationships between various patient characteristics and the appropriateness ratings were examined, along with the relationships between hospital-level inappropriateness, for DC and 2 other hospital-level variables (hospital DC volume and percutaneous coronary intervention inappropriateness). Of the 8986 patients who could be rated for appropriateness, 35.3% were rated as appropriate, 39.8% as uncertain, and 24.9% as inappropriate. Of the 2240 patients rated as inappropriate, 56.7% were asymptomatic/had no previous stress test/had low or intermediate global coronary artery disease risk, 36.0% had a previous stress test with low-risk findings and no symptoms, and 7.3% were symptomatic/had no previous stress test/had low pretest probability. The median hospital-level inappropriateness rate was 28.5%, with a maximum of 48.8% and a minimum of 8.6%. Hospital-level inappropriateness was not related to hospital volume or inappropriateness for percutaneous coronary intervention.

Conclusions—

One quarter of patients undergoing DC for suspected coronary artery disease were rated as inappropriate for the procedure, approximately two thirds of these inappropriate patients had no previous stress test, and ≈90% of inappropriate patients with no previous stress test were asymptomatic with low or intermediate global risk scores.
Stenopterobia cataractarum sp. nov. (Bacillariophyta), a new benthic diatom from a waterfall in Zambia, Africa
Authors: Cocquyt Christine , Taylor Jonathan Charles , Wetzel Carlos
Published: January 2014

Rivers, streams and associated habitats have been sampled for diatoms in the relatively understudied Congo and Zambezi sister basins. The primary purpose of the sampling effort was to collect samples for biological monitoring purposes and the establishment of a diatom-based monitoring programme. However, a large number of possibly endemic and novel taxa have been encountered in this region making the application of diatom-based indices at a species level difficult. In this paper we describe a new species of Stenopterobia from the Ntumbachushi Falls in the Luapula Province of Zambia. This taxon is closely related to Stenopterobia delicatissima but chiefly differentiated by a lower number of striae, a well-defined unornamented lanceolate axial area and shortened ribs which do not fuse with the fenestrae. This taxon also shows some similarity to Stenopterobia delicatissima var. ghanaensis but the valves are consistently narrower.
The Concept of Essential Climate Variables in Support of Climate Research, Applications, and Policy
Authors: Bojinski Stephan , Verstraete Michel , Peterson Thomas C. , Richter Carolin , Simmons Adrian , Zemp Michael
Published: January 2014

Climate research, monitoring, prediction, and related services rely on accurate observations of the atmosphere, land, and ocean, adequately sampled globally and over sufficiently long time periods. The Global Climate Observing System, set up under the auspices of United Nations organizations and the International Council for Science to help ensure the availability of systematic observations of climate, developed the concept of essential climate variables (ECVs). ECV data records are intended to provide reliable, traceable, observation-based evidence for a range of applications, including monitoring, mitigating, adapting to, and attributing climate changes, as well as the empirical basis required to understand past, current, and possible future climate variability. The ECV concept has been broadly adopted worldwide as the guiding basis for observing climate, including by the United Nations Framework Convention on Climate Change (UNFCCC), WMO, and space agencies operating Earth observation satellites.

This paper describes the rationale for these ECVs and their current selection, based on the principles of feasibility, relevance, and cost effectiveness. It also provides a view of how the ECV concept could evolve as a guide for rational and evidence-based monitoring of climate and environment. Selected examples are discussed to highlight the benefits, limitations, and future evolution of this approach.

The article is intended to assist program managers to set priorities for climate observation, dataset generation and related research: for instance, within the emerging Global Framework for Climate Services (GFCS). It also helps the observation community and individual researchers to contribute to systematic climate observation, by promoting understanding of ECV choices and the opportunities to influence their evolution.