bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: A pilot study
Authors: IKEDA Takaharu , KANAZAWA Nobuo , FURUKAWA Fukumi 
Published: December 2011

AbstractHydroxychloroquine (HCQ) is used as the first‐line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment. Arthralgia improved in all three cases with arthralgia and general malaise also improved in two of the three cases who had complained. In three cases who discontinued HCQ therapy after 16 weeks of treatment, their skin lesions and general malaise worsened soon, and after the resumption of HCQ therapy these symptoms improved again. The mean serum triglyceride and total cholesterol levels also decreased significantly at the end of this study. Our results suggest that HCQ might be effective for Japanese SLE skin lesions and CLE, and support the studies which reported that HCQ prevented clinical flare ups of SLE. An additional effect to improve lipid profiles was also observed in our Japanese cases. It is necessary to confirm that these effects are reproducible when Japanese lupus erythematosus cases are given HCQ.
Does minimum pricing reduce alcohol consumption? The experience of a Canadian province
Authors: Stockwell Tim , Auld M. Christopher , Zhao Jinhui , Martin Gina 
Published: December 2011

ABSTRACTAims Minimum alcohol prices in British Columbia have been adjusted intermittently over the past 20 years. The present study estimates impacts of these adjustments on alcohol consumption.Design Time–series and longitudinal models of aggregate alcohol consumption with price and other economic data as independent variables.Setting British Columbia (BC), Canada.Participants The population of British Columbia, Canada, aged 15 years and over.Measurements Data on alcohol prices and sales for different beverages were provided by the BC Liquor Distribution Branch for 1989–2010. Data on household income were sourced from Statistics Canada.Findings  Longitudinal estimates suggest that a 10% increase in the minimum price of an alcoholic beverage reduced its consumption relative to other beverages by 16.1% (P < 0.001). Time–series estimates indicate that a 10% increase in minimum prices reduced consumption of spirits and liqueurs by 6.8% (P = 0.004), wine by 8.9% (P = 0.033), alcoholic sodas and ciders by 13.9% (P = 0.067), beer by 1.5% (P = 0.043) and all alcoholic drinks by 3.4% (P = 0.007).Conclusions Increases in minimum prices of alcoholic beverages can substantially reduce alcohol consumption.
Downregulation of BCL2 by AT‐101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner
Authors: Masood Aisha , Chitta Kasyapa , Paulus Aneel , Khan A. Nazmul H. , Sher Taimur , Ersing Noreen , Miller Kena C. , Manfredi Deborah , Ailawadhi Sikander , Borrelo Ivan , Lee Kelvin P. , Chanan‐Khan Asher 
Published: December 2011

SummaryOver‐expression of anti‐apoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti‐CLL effects of CD20 targeting monoclonal antibody, rituximab. Here, we investigated the mechanism of immune‐directed killing of lenalidomide in CLL and evaluated if concurrent targeting of CD20 and BCL2 can enhance this effect. In vitro treatment with lenalidomide enhanced the antibody‐mediated cellular cytotoxicity (ADCC) directed by rituximab in autologous leukaemic cells. Furthermore, peripheral blood mononuclear cells obtained from patients after treatment with lenalidomide and rituximab showed increased ADCC in vitro versus control (pre‐treatment sample). This effect was further enhanced with pre‐treatment of tumour cells with AT‐101 (a BH3 mimetic that functions as BCL2 antagonist). Our data suggest that AT‐101 in combination with lenalidomide can potentially be an effective therapeutic regimen for CLL.
Can plasma exchange therapy induce regulatory T lymphocytes in multiple sclerosis patients?
Authors: Jamshidian A , Gharagozloo M 
Published: December 2011

SummaryPlasma exchange is used increasingly as an individual therapeutic decision for treating of severe, steroid-resistant relapses of multiple sclerosis (MS). However, given that its mechanism of action in this CD4+ T cell-mediated autoimmune disease remains unknown, it is not yet considered as a routine therapy for this prevalent neuroimmune disorder. In this regard, we hypothesized that plasma exchange, by depleting the body of inflammatory mediators that acts as providers of co-stimulatory signals for the adaptive immune system, provides the immune system with an exceptional break for de-novo recognition of autoantigens in a tolerogenic manner. This may lead to an increase in the frequency and function of myelin-specific regulatory T cells. For evaluating this we suggest some in vitro and in vivo studies to analyse the effects of varied dilutions of normal and MS plasmas on the induction of regulatory T cells or on the function of isolated and purified regulatory T cells. Clarifying the effects of therapeutic plasma exchange on regulatory T cells as the major controllers of autoimmune responses may provide us with strong evidence to use this procedure as a disease-modifying treatment in remission phase for reducing the rate and severity of future attacks, in addition to more trustworthy therapy in severe relapses of MS.
Hyperthyrotropinemia at 2 weeks of age indicates thyroid dysfunction and predicts the occurrence of delayed elevation of thyrotropin in very low birth weight infants
Authors: Niwa Fusako , Kawai Masahiko , Kanazawa Hoshinori , Iwanaga Kougorou , Matsukura Takashi , Hasegawa Takeshi , Heike Toshio 
Published: December 2011

SummaryBackground  For preterm infants, transient hypothyroxinemia of prematurity and transient primary hypothyroidism, especially with delayed elevation of serum thyrotropin (TSH), are important.Methods  To address the above two issues, we performed thyrotropin‐releasing hormone (TRH) stimulation tests at about 2 weeks of age for 31 preterm infants with a gestational age of 30 weeks or less.Results  For basal TSH levels, 68% of infants (21 of 31) showed normal values (TSH < 10 mU/l) and 32% of infants (10 of 31) showed higher values (four infants: TSH 10–15 mU/l, six infants: TSH > 15 mU/l). Peak TSH values in response to TRH stimulation tests ranged from 9·76 to 114·8 mU/l. All infants showed a significant response to TRH stimulation tests. Only 9·5% of infants (two of 21) with normal basal TSH values showed a hyperresponse (peak TSH > 45 mU/l), whereas 80% of infants (eight of 10) who had higher basal TSH values showed a hyperresponse. All infants who showed mildly elevated basal TSH values (TSH 10–15 mU/l) and a hyperresponse to TRH stimulation tests showed delayed elevation of basal TSH values (TSH > 15 mU/l) later.Conclusions  Thyrotropin‐releasing hormone stimulation tests at about 2 weeks of age suggested that the hypothalamic–pituitary–thyroid axis might be established even in extremely premature infants. Basal increased TSH levels (TSH > 10 mU/l) and a hyperresponse to TRH stimulation tests (peak TSH > 45 mU/l) suggested subclinical thyroid dysfunction. Serum TSH values at about 2 weeks of age could be useful for the prediction of delayed TSH elevation.
Evolution of the research collaboration network in a productive department
Authors: Katerndahl David 
Published: December 2011

AbstractRationale  Understanding collaboration networks can facilitate the research growth of new or developing departments. The purpose of this study was to use social network analysis to understand how the research collaboration network evolved within a productive department.Methods  Over a 13‐year period, a departmental faculty completed an annual survey describing their research collaborations. Data were analyzed using social network analysis. Network measures focused on connectedness, distance, groupings and heterogeneity of distribution, while measures for the research director and external collaboration focused on centrality and roles within the network. Longitudinal patterns of network collaboration were assessed using Simulation Investigation for Empirical Network Analysis software (University of Groningen, Groningen, Netherlands).Results  Based upon the number of active research projects, research development can be divided into three phases. The initial development phase was characterized by increasing centralization and collaboration focused within a single subject area. During the maintenance phase, measures went through cycles, possibly because of changes in faculty composition. While the research director was not a ‘key player’ within the network during the first several years, external collaboration played a central role during all phases. Longitudinal analysis found that forming ties was more likely when the opportunity for network closure existed and when those around you are principal investigators (PIs).Conclusion  Initial development of research relied heavily upon a centralized network involving external collaboration; a central position of the research director during research development was not important. Changes in collaboration depended upon faculty gender and tenure track as well as transitivity and the ‘popularity of PIs’.
The potential for targeted surveillance of live fish movements in Scotland
Authors: Green D M , Werkman M , Munro L A 
Published: December 2011

AbstractThe network structure of the movements of live fish in the Scottish aquaculture industry has recently been demonstrated for 2003. In this paper, we enlarge this analysis to a longer 3‐year period from 2002 to 2004, the new data allowing complete coverage of at least one production cycle. The resulting network contains slightly more sites than that for a single year and is denser with more arcs (directed site‐to‐site connections) present, but otherwise features recognizable in the 1‐year network are still recognizable in the 3‐year network. Arc‐removal algorithms (a proxy for targeted surveillance) were identified that could successfully reduce the portion of the network reachable from a node (a proxy for potential epidemic size) by approximately one‐third by removing as few as four arcs. This results from the high centrality of particular nodes and arcs. A strong community structure was identified in the network, corresponding with species farmed, but only weakly geographical, with a high proportion of arcs occurring between management areas and catchments.
Studies on the effect of temperature and pH on the inactivation of fish viral and bacterial pathogens
Authors: Dixon P F , Smail D A , Algoët M , Hastings T S , Bayley A , Byrne H , Dodge M , Garden A , Joiner C , Roberts E , Verner‐Jeffreys D , Thompson F 
Published: December 2011

AbstractDisposal of fish by‐products in the European Community must comply with Regulation (EC) No 1069/2009 which categorizes animal by‐products according to risk, and specifies methods of disposal of by‐products according to that risk. There is provision under the regulation for composting or ensiling to be used for by‐products from aquatic animals. Biosecurity considerations require knowledge of the parameters of time and temperature, or time and pH, required to inactivate any fish pathogens that may be present. To provide those data, we undertook laboratory studies on the inactivation of a number of fish pathogenic viruses and bacteria at 60 °C, pH 4.0 and pH 12.0 as a preliminary to conducting subsequent trials with the most resistant viruses and bacteria in fish tissues. The most resistant bacterium to 60 °C, pH 4.0 as well as pH 12.0 was Lactococcus garvieae. Its concentration was reduced to the level of sensitivity of the test after 24–48 h exposure to 60 °C, but it survived for at least 7 days at pH 4.0 and 14 days at pH 12.0. The most resistant virus to 60 °C was infectious pancreatic necrosis virus, and to pH 12.0 was infectious salmon anaemia virus. The majority of the viruses tested survived exposure to pH 4.0 for up to 28 days. The results suggest that the process of acid ensiling alone is not an effective method for the inactivation of many viral and bacterial pathogens, and fish by‐products would need further treatment by a method approved under the regulation following ensiling, whereas alkaline or heat treatment are likely to provide an increased degree of biosecurity for on‐farm processing of mortalities.
Effect of aging on the morphology of bitumen by atomic force microscopy
Authors: ZHANG H.L. , YU J.Y. , FENG Z.G. , XUE L.H. , WU S.P. 
Published: December 2011

SummaryEffect of aging on the morphology of bitumen was investigated. Two bitumens were aged according to the thin film oven test (TFOT), pressure aging vessel (PAV) test and ultraviolet (UV) radiation, respectively. The morphology of the binders before and after aging was characterized by atomic force microscopy. The physical properties and chemical compositions of the binders were also measured. The results showed that aging affected the bitumen morphology significantly. Aging increased the overall surface stiffness of the bitumen and made the bitumen surface more solid‐like. The extent of these changes was dependent on aging conditions. TFOT decreased the contrast between the dispersed domains and the matrix, which contributed to the single‐phase trend of the binders. The effect of PAV aging on morphology of the binders was dependent on the base bitumen. In one case, it further accelerated the single‐phase trend of bitumen in comparison with that after TFOT. In the other case, it caused the phase separation of bitumen. In both cases, PAV aging increased the surface roughness of the binders obviously. As a result of UV aging, the contrast between the matrix phase and dispersed phase was increased due to the difference in sensitivity to UV radiation of the bitumen molecules, which caused or further promoted the phase separation in the binders. Regardless of the aging procedure carried out, a strong correlation was observed between the changes in morphology and physical properties as well as chemical compositions of the binders before and after aging.
Quantification of plant cell coupling with three‐dimensional photoactivation microscopy
Authors: LIESCHE J. , SCHULZ A. 
Published: December 2011

SummaryPlant cells are directly connected by plasmodesmata that form channels through the cell wall and enable the intercellular movement of cytosolic solutes, membrane lipids and signalling molecules. Transport through plasmodesmata is regulated not only by a fixed size‐exclusion limit, but also by physiological and pathological adaptation. To understand plant cell communication, carbon allocation and pathogen attack, the capacities for a specific molecule to pass a specific cell–wall interface is an essential parameter. So far, the degree of cell coupling was derived from frequency and diameter of plasmodesmata in relevant tissues as assessed by electron microscopy of fixed material. However, plasmodesmata functionality and capacity can only be determined in live material, not from electron microscopy, which is static and prone to fixation artefacts. Plasmodesmata functionality was a few times assessed using fluorescent tracers with diffusion properties similar to cytosolic solutes. Here, we used three‐dimensional photoactivation microscopy to quantify plasmodesmata‐mediated cell–wall permeability between living Cucurbita maxima leaf mesophyll cells with caged fluorescein as tracer. For the first time, all necessary functional and anatomical data were gathered for each individual cell from three‐dimensional time series. This approach utilized a confocal microscope equipped with resonant scanner, which provides the high acquisition speed necessary to record optical sections of whole cells and offers time resolution high enough to follow the kinetics of photoactivation. The results were compared to two‐dimensional measurements, which are shown to give a good estimate of cell coupling adequate for homogenous tissues. The two‐dimensional approach is limited whenever tissues interfaces are studied that couple different cell types with diverse cell geometries.
Who is eating what: diet assessment using next generation sequencing
Authors: POMPANON FRANCOIS , DEAGLE BRUCE E. , SYMONDSON WILLIAM O. C. , BROWN DAVID S. , JARMAN SIMON N. , TABERLET PIERRE 
Published: December 2011

AbstractThe analysis of food webs and their dynamics facilitates understanding of the mechanistic processes behind community ecology and ecosystem functions. Having accurate techniques for determining dietary ranges and components is critical for this endeavour. While visual analyses and early molecular approaches are highly labour intensive and often lack resolution, recent DNA‐based approaches potentially provide more accurate methods for dietary studies. A suite of approaches have been used based on the identification of consumed species by characterization of DNA present in gut or faecal samples. In one approach, a standardized DNA region (DNA barcode) is PCR amplified, amplicons are sequenced and then compared to a reference database for identification. Initially, this involved sequencing clones from PCR products, and studies were limited in scale because of the costs and effort required. The recent development of next generation sequencing (NGS) has made this approach much more powerful, by allowing the direct characterization of dozens of samples with several thousand sequences per PCR product, and has the potential to reveal many consumed species simultaneously (DNA metabarcoding). Continual improvement of NGS technologies, on‐going decreases in costs and current massive expansion of reference databases make this approach promising. Here we review the power and pitfalls of NGS diet methods. We present the critical factors to take into account when choosing or designing a suitable barcode. Then, we consider both technical and analytical aspects of NGS diet studies. Finally, we discuss the validation of data accuracy including the viability of producing quantitative data.
Identification of a protein kinase A regulatory subunit from Leishmania having importance in metacyclogenesis through induction of autophagy
Authors: Bhattacharya Arijit , Biswas Arunima , Das Pijush K. 
Published: December 2011

SummarycAMP‐mediated responses act as modulators of environmental sensing and cellular differentiation of many kinetoplastidae parasites including Leishmania. Although cAMP synthesizing (adenylate cyclase) and degrading (phosphodiesterase) enzymes have been cloned and characterized from Leishmania, no cAMP‐binding effector molecule has yet been identified from this parasite. In this study, a regulatory subunit of cAMP‐dependent protein kinase (Ldpkar1), homologous to mammalian class I cAMP‐dependent protein kinase regulatory subunit, has been identified from L. donovani. Further characterization suggested possible interaction of LdPKAR1 with PKA catalytic subunits and inhibition of PKA activity. This PKA regulatory subunit is expressed in all life cycle stages and its expression attained maximum level in stationary phase promastigotes, which are biochemically similar to the infective metacyclic promastigotes. Starvation condition, the trigger for metacyclogenesis in the parasite, elevates LdPKAR1 expression and under starvation condition promastigotes overexpressing Ldpkar1 attained metacyclic features earlier than normal cells. Furthermore, Ldpkar1 overexpression accelerates autophagy, a starvation‐induced cytological event necessary for metacyclogenesis and amastigote formation. Conditional silencing of Ldpkar1 delays the induction of autophagy in the parasite. The study, for the first time, reports the identification of a functional cAMP‐binding effector molecule from Leishmania that may modulate important cytological events affecting metacyclogenesis.
Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects
Authors: Loke J , Ostrer H 
Published: December 2011

Loke J, Ostrer H. Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects.DNA sequencing of candidate genes or whole exomes on a diagnostic or investigational basis will yield a plethora of variants of uncertain significance whose potential phenotypic roles cannot be readily demonstrated by prediction programs, SNP databases nor conventional genetic analysis. Many variants may produce phenotypic changes in the encoded proteins by affecting the quantity, post‐translational modification or protein interactions. Here, we establish the application of the method of flow cytometry following immunoprecipitation to show that known protein interactions are altered in the B‐lymphoblastoid cells of patients with 46,XY gonadal dysgenesis arising from mutations in the MAP3K1 gene. This method can be scaled readily to test multiple interactions for many variants simultaneously from available tissues as well as quantify the effects of variants on protein accumulation and post‐translational modification, thus providing an efficient means for screening variants of uncertain significance for phenotypic effects.